id	sid	tid	token	lemma	pos
admet-10	1	1	manuscript	manuscript	PROPN
admet-10	1	2	doi	doi	PROPN
admet-10	1	3	:	:	PUNCT
admet-10	1	4	10.5599	10.5599	NUM
admet-10	1	5	/	/	SYM
admet-10	1	6	admet.1.4.10	admet.1.4.10	PROPN
admet-10	1	7	63	63	NUM
admet-10	1	8	admet	admet	NOUN
admet-10	1	9	&	&	CCONJ
admet-10	1	10	dmpk	dmpk	PROPN
admet-10	1	11	1(4	1(4	NUM
admet-10	1	12	)	)	PUNCT
admet-10	1	13	(	(	PUNCT
admet-10	1	14	2013	2013	NUM
admet-10	1	15	)	)	PUNCT
admet-10	1	16	63	63	NUM
admet-10	1	17	-	-	SYM
admet-10	1	18	75	75	NUM
admet-10	1	19	;	;	PUNCT
admet-10	1	20	doi	doi	NOUN
admet-10	1	21	:	:	PUNCT
admet-10	1	22	10.5599	10.5599	NUM
admet-10	1	23	/	/	SYM
admet-10	1	24	admet.1.4.10	admet.1.4.10	ADJ
admet-10	1	25	open	open	ADJ
admet-10	1	26	access	access	NOUN
admet-10	1	27	:	:	PUNCT
admet-10	1	28	issn	issn	PROPN
admet-10	1	29	:	:	PUNCT
admet-10	1	30	1848	1848	NUM
admet-10	1	31	-	-	SYM
admet-10	1	32	7718	7718	NUM
admet-10	1	33	http://www.pub.iapchem.org/ojs/index.php/admet/index	http://www.pub.iapchem.org/ojs/index.php/admet/index	NOUN
admet-10	1	34	mini	mini	NOUN
admet-10	1	35	review	review	NOUN
admet-10	1	36	estimating	estimate	VERB
admet-10	1	37	the	the	DET
admet-10	1	38	“	"	PUNCT
admet-10	1	39	first	first	ADJ
admet-10	1	40	in	in	ADP
admet-10	1	41	human	human	NOUN
admet-10	1	42	”	"	PUNCT
admet-10	1	43	dose	dose	NOUN
admet-10	1	44	–	–	PUNCT
admet-10	1	45	a	a	DET
admet-10	1	46	revisit	revisit	NOUN
admet-10	1	47	with	with	ADP
admet-10	1	48	particular	particular	ADJ
admet-10	1	49	emphasis	emphasis	NOUN
admet-10	1	50	on	on	ADP
admet-10	1	51	oncology	oncology	NOUN
admet-10	1	52	drugs	drug	NOUN
admet-10	1	53	kin	kin	PROPN
admet-10	1	54	tam	tam	PROPN
admet-10	1	55	faculty	faculty	PROPN
admet-10	1	56	of	of	ADP
admet-10	1	57	health	health	NOUN
admet-10	1	58	science	science	NOUN
admet-10	1	59	,	,	PUNCT
admet-10	1	60	university	university	PROPN
admet-10	1	61	of	of	ADP
admet-10	1	62	macau	macau	PROPN
admet-10	1	63	,	,	PUNCT
admet-10	1	64	macau	macau	PROPN
admet-10	1	65	,	,	PUNCT
admet-10	1	66	china	china	PROPN
admet-10	1	67	e	e	PROPN
admet-10	1	68	-	-	NOUN
admet-10	1	69	mail	mail	NOUN
admet-10	1	70	:	:	PUNCT
admet-10	1	71	kintam@umac.mo	kintam@umac.mo	PROPN
admet-10	1	72	;	;	PUNCT
admet-10	1	73	tel	tel	PROPN
admet-10	1	74	.	.	PUNCT
admet-10	1	75	:	:	PUNCT
admet-10	2	1	+853	+853	NUM
admet-10	2	2	-	-	PUNCT
admet-10	2	3	8397	8397	NUM
admet-10	2	4	-	-	SYM
admet-10	2	5	8444	8444	NUM
admet-10	2	6	;	;	PUNCT
admet-10	2	7	fax	fax	NOUN
admet-10	2	8	:	:	PUNCT
admet-10	2	9	+853	+853	NOUN
admet-10	2	10	-	-	PUNCT
admet-10	2	11	8397	8397	NUM
admet-10	2	12	-	-	SYM
admet-10	2	13	8500	8500	NUM
admet-10	2	14	received	receive	VERB
admet-10	2	15	:	:	PUNCT
admet-10	2	16	june	june	PROPN
admet-10	2	17	30	30	NUM
admet-10	2	18	th	th	NUM
admet-10	2	19	,	,	PUNCT
admet-10	2	20	2013	2013	NUM
admet-10	2	21	;	;	PUNCT
admet-10	2	22	revised	revise	VERB
admet-10	2	23	:	:	PUNCT
admet-10	2	24	october	october	PROPN
admet-10	2	25	21	21	NUM
admet-10	2	26	st	st	PROPN
admet-10	2	27	,	,	PUNCT
admet-10	2	28	2013	2013	NUM
admet-10	2	29	;	;	PUNCT
admet-10	2	30	published	publish	VERB
admet-10	2	31	:	:	PUNCT
admet-10	2	32	december	december	PROPN
admet-10	2	33	16	16	NUM
admet-10	2	34	,	,	PUNCT
admet-10	2	35	2013	2013	NUM
admet-10	2	36	abstract	abstract	NOUN
admet-10	2	37	the	the	DET
admet-10	2	38	initial	initial	ADJ
admet-10	2	39	dose	dose	NOUN
admet-10	2	40	selection	selection	NOUN
admet-10	2	41	is	be	AUX
admet-10	2	42	one	one	NUM
admet-10	2	43	of	of	ADP
admet-10	2	44	the	the	DET
admet-10	2	45	important	important	ADJ
admet-10	2	46	steps	step	NOUN
admet-10	2	47	for	for	ADP
admet-10	2	48	any	any	DET
admet-10	2	49	investigative	investigative	ADJ
admet-10	2	50	new	new	ADJ
admet-10	2	51	drug	drug	NOUN
admet-10	2	52	(	(	PUNCT
admet-10	2	53	ind	ind	NOUN
admet-10	2	54	)	)	PUNCT
admet-10	2	55	entering	enter	VERB
admet-10	2	56	the	the	DET
admet-10	2	57	first	first	ADJ
admet-10	2	58	clinical	clinical	ADJ
admet-10	2	59	study	study	NOUN
admet-10	2	60	in	in	ADP
admet-10	2	61	humans	human	NOUN
admet-10	2	62	.	.	PUNCT
admet-10	3	1	in	in	ADP
admet-10	3	2	this	this	DET
admet-10	3	3	mini	mini	ADJ
admet-10	3	4	review	review	NOUN
admet-10	3	5	,	,	PUNCT
admet-10	3	6	we	we	PRON
admet-10	3	7	will	will	AUX
admet-10	3	8	discuss	discuss	VERB
admet-10	3	9	the	the	DET
admet-10	3	10	no	no	DET
admet-10	3	11	observed	observed	ADJ
admet-10	3	12	adverse	adverse	ADJ
admet-10	3	13	effect	effect	NOUN
admet-10	3	14	level	level	NOUN
admet-10	3	15	(	(	PUNCT
admet-10	3	16	noael	noael	NUM
admet-10	3	17	)	)	PUNCT
admet-10	3	18	and	and	CCONJ
admet-10	3	19	the	the	DET
admet-10	3	20	minimum	minimum	ADJ
admet-10	3	21	anticipated	anticipate	VERB
admet-10	3	22	biological	biological	ADJ
admet-10	3	23	effect	effect	NOUN
admet-10	3	24	level	level	NOUN
admet-10	3	25	(	(	PUNCT
admet-10	3	26	mabel	mabel	NOUN
admet-10	3	27	)	)	PUNCT
admet-10	3	28	approaches	approach	VERB
admet-10	3	29	for	for	ADP
admet-10	3	30	the	the	DET
admet-10	3	31	estimation	estimation	NOUN
admet-10	3	32	of	of	ADP
admet-10	3	33	the	the	DET
admet-10	3	34	first	first	ADJ
admet-10	3	35	in	in	ADP
admet-10	3	36	human	human	ADJ
admet-10	3	37	(	(	PUNCT
admet-10	3	38	fih	fih	NOUN
admet-10	3	39	)	)	PUNCT
admet-10	3	40	dose	dose	PROPN
admet-10	3	41	.	.	PUNCT
admet-10	4	1	particular	particular	ADJ
admet-10	4	2	attention	attention	NOUN
admet-10	4	3	will	will	AUX
admet-10	4	4	be	be	AUX
admet-10	4	5	placed	place	VERB
admet-10	4	6	on	on	ADP
admet-10	4	7	the	the	DET
admet-10	4	8	development	development	NOUN
admet-10	4	9	of	of	ADP
admet-10	4	10	the	the	DET
admet-10	4	11	fih	fih	NOUN
admet-10	4	12	dose	dose	VERB
admet-10	4	13	for	for	ADP
admet-10	4	14	oncology	oncology	NOUN
admet-10	4	15	drugs	drug	NOUN
admet-10	4	16	.	.	PUNCT
admet-10	5	1	keywords	keyword	NOUN
admet-10	5	2	initial	initial	ADJ
admet-10	5	3	dose	dose	NOUN
admet-10	5	4	;	;	PUNCT
admet-10	5	5	starting	start	VERB
admet-10	5	6	dose	dose	PROPN
admet-10	5	7	;	;	PUNCT
admet-10	5	8	clinical	clinical	ADJ
admet-10	5	9	trial	trial	NOUN
admet-10	5	10	;	;	PUNCT
admet-10	5	11	noael	noael	NUM
admet-10	5	12	;	;	PUNCT
admet-10	5	13	mabel	mabel	PROPN
admet-10	5	14	;	;	PUNCT
admet-10	5	15	cytotoxic	cytotoxic	ADJ
admet-10	5	16	;	;	PUNCT
admet-10	5	17	anticancer	anticancer	NOUN
admet-10	5	18	;	;	PUNCT
admet-10	5	19	combination	combination	NOUN
admet-10	5	20	therapy	therapy	NOUN
admet-10	5	21	study	study	NOUN
admet-10	5	22	1	1	NUM
admet-10	5	23	.	.	PUNCT
admet-10	6	1	introduction	introduction	NOUN
admet-10	6	2	estimating	estimate	VERB
admet-10	6	3	the	the	DET
admet-10	6	4	first	first	ADJ
admet-10	6	5	in	in	ADP
admet-10	6	6	human	human	ADJ
admet-10	6	7	(	(	PUNCT
admet-10	6	8	fih	fih	NOUN
admet-10	6	9	)	)	PUNCT
admet-10	6	10	dose	dose	NOUN
admet-10	6	11	is	be	AUX
admet-10	6	12	one	one	NUM
admet-10	6	13	of	of	ADP
admet-10	6	14	the	the	DET
admet-10	6	15	initial	initial	ADJ
admet-10	6	16	steps	step	NOUN
admet-10	6	17	in	in	ADP
admet-10	6	18	the	the	DET
admet-10	6	19	clinical	clinical	ADJ
admet-10	6	20	development	development	NOUN
admet-10	6	21	of	of	ADP
admet-10	6	22	any	any	DET
admet-10	6	23	molecule	molecule	NOUN
admet-10	6	24	that	that	PRON
admet-10	6	25	has	have	AUX
admet-10	6	26	successfully	successfully	ADV
admet-10	6	27	gone	go	VERB
admet-10	6	28	through	through	ADP
admet-10	6	29	all	all	PRON
admet-10	6	30	of	of	ADP
admet-10	6	31	the	the	DET
admet-10	6	32	hurdles	hurdle	NOUN
admet-10	6	33	in	in	ADP
admet-10	6	34	preclinical	preclinical	ADJ
admet-10	6	35	evaluations	evaluation	NOUN
admet-10	6	36	.	.	PUNCT
admet-10	7	1	it	it	PRON
admet-10	7	2	is	be	AUX
admet-10	7	3	an	an	DET
admet-10	7	4	important	important	ADJ
admet-10	7	5	parameter	parameter	NOUN
admet-10	7	6	in	in	ADP
admet-10	7	7	the	the	DET
admet-10	7	8	fih	fih	NOUN
admet-10	7	9	clinical	clinical	ADJ
admet-10	7	10	trials	trial	NOUN
admet-10	7	11	,	,	PUNCT
admet-10	7	12	since	since	SCONJ
admet-10	7	13	a	a	DET
admet-10	7	14	high	high	ADJ
admet-10	7	15	starting	starting	NOUN
admet-10	7	16	dose	dose	NOUN
admet-10	7	17	may	may	AUX
admet-10	7	18	cause	cause	VERB
admet-10	7	19	serious	serious	ADJ
admet-10	7	20	toxicity	toxicity	NOUN
admet-10	7	21	in	in	ADP
admet-10	7	22	volunteers	volunteer	NOUN
admet-10	7	23	,	,	PUNCT
admet-10	7	24	while	while	SCONJ
admet-10	7	25	a	a	DET
admet-10	7	26	low	low	ADJ
admet-10	7	27	starting	starting	NOUN
admet-10	7	28	dose	dose	NOUN
admet-10	7	29	could	could	AUX
admet-10	7	30	prolong	prolong	VERB
admet-10	7	31	the	the	DET
admet-10	7	32	dose	dose	NOUN
admet-10	7	33	escalation	escalation	NOUN
admet-10	7	34	/	/	SYM
admet-10	7	35	optimisation	optimisation	NOUN
admet-10	7	36	,	,	PUNCT
admet-10	7	37	leading	lead	VERB
admet-10	7	38	to	to	ADP
admet-10	7	39	unnecessary	unnecessary	ADJ
admet-10	7	40	delay	delay	NOUN
admet-10	7	41	in	in	ADP
admet-10	7	42	the	the	DET
admet-10	7	43	clinical	clinical	ADJ
admet-10	7	44	programs	program	NOUN
admet-10	7	45	.	.	PUNCT
admet-10	8	1	adverse	adverse	ADJ
admet-10	8	2	drug	drug	NOUN
admet-10	8	3	reactions	reaction	NOUN
admet-10	8	4	do	do	AUX
admet-10	8	5	occur	occur	VERB
admet-10	8	6	in	in	ADP
admet-10	8	7	clinical	clinical	ADJ
admet-10	8	8	trials	trial	NOUN
admet-10	8	9	[	[	X
admet-10	8	10	1	1	NUM
admet-10	8	11	]	]	PUNCT
admet-10	8	12	.	.	PUNCT
admet-10	9	1	it	it	PRON
admet-10	9	2	is	be	AUX
admet-10	9	3	unethical	unethical	ADJ
admet-10	9	4	to	to	PART
admet-10	9	5	expose	expose	VERB
admet-10	9	6	human	human	ADJ
admet-10	9	7	subjects	subject	NOUN
admet-10	9	8	to	to	PART
admet-10	9	9	poorly	poorly	ADV
admet-10	9	10	executed	execute	VERB
admet-10	9	11	trials	trial	NOUN
admet-10	9	12	[	[	X
admet-10	9	13	2	2	NUM
admet-10	9	14	]	]	PUNCT
admet-10	9	15	.	.	PUNCT
admet-10	10	1	clearly	clearly	ADV
admet-10	10	2	,	,	PUNCT
admet-10	10	3	protecting	protect	VERB
admet-10	10	4	the	the	DET
admet-10	10	5	volunteers	volunteer	NOUN
admet-10	10	6	is	be	AUX
admet-10	10	7	paramount	paramount	ADJ
admet-10	10	8	,	,	PUNCT
admet-10	10	9	especially	especially	ADV
admet-10	10	10	in	in	ADP
admet-10	10	11	the	the	DET
admet-10	10	12	first	first	ADJ
admet-10	10	13	human	human	ADJ
admet-10	10	14	trial	trial	NOUN
admet-10	10	15	using	use	VERB
admet-10	10	16	healthy	healthy	ADJ
admet-10	10	17	individuals	individual	NOUN
admet-10	10	18	.	.	PUNCT
admet-10	11	1	designing	design	VERB
admet-10	11	2	the	the	DET
admet-10	11	3	appropriate	appropriate	ADJ
admet-10	11	4	fih	fih	NOUN
admet-10	11	5	dose	dose	NOUN
admet-10	11	6	requires	require	VERB
admet-10	11	7	close	close	ADJ
admet-10	11	8	collaboration	collaboration	NOUN
admet-10	11	9	among	among	ADP
admet-10	11	10	the	the	DET
admet-10	11	11	pharmacokineticists	pharmacokineticist	NOUN
admet-10	11	12	,	,	PUNCT
admet-10	11	13	toxicologists	toxicologist	NOUN
admet-10	11	14	,	,	PUNCT
admet-10	11	15	and	and	CCONJ
admet-10	11	16	preclinical	preclinical	ADJ
admet-10	11	17	scientists	scientist	NOUN
admet-10	11	18	.	.	PUNCT
admet-10	12	1	data	datum	NOUN
admet-10	12	2	from	from	ADP
admet-10	12	3	preclinical	preclinical	ADJ
admet-10	12	4	experiments	experiment	NOUN
admet-10	12	5	such	such	ADJ
admet-10	12	6	as	as	ADP
admet-10	12	7	animal	animal	NOUN
admet-10	12	8	,	,	PUNCT
admet-10	12	9	modelling	modelling	NOUN
admet-10	12	10	,	,	PUNCT
admet-10	12	11	and	and	CCONJ
admet-10	12	12	pharmacokinetic	pharmacokinetic	ADJ
admet-10	12	13	data	datum	NOUN
admet-10	12	14	help	help	NOUN
admet-10	12	15	to	to	PART
admet-10	12	16	determine	determine	VERB
admet-10	12	17	the	the	DET
admet-10	12	18	initial	initial	ADJ
admet-10	12	19	dose	dose	NOUN
admet-10	12	20	and	and	CCONJ
admet-10	12	21	dosing	dose	VERB
admet-10	12	22	interval	interval	NOUN
admet-10	12	23	in	in	ADP
admet-10	12	24	early	early	ADJ
admet-10	12	25	clinical	clinical	ADJ
admet-10	12	26	development	development	NOUN
admet-10	12	27	.	.	PUNCT
admet-10	13	1	in	in	ADP
admet-10	13	2	2005	2005	NUM
admet-10	13	3	,	,	PUNCT
admet-10	13	4	the	the	DET
admet-10	13	5	us	us	PROPN
admet-10	13	6	food	food	NOUN
admet-10	13	7	and	and	CCONJ
admet-10	13	8	drug	drug	PROPN
admet-10	13	9	administration	administration	PROPN
admet-10	13	10	(	(	PUNCT
admet-10	13	11	fda	fda	PROPN
admet-10	13	12	)	)	PUNCT
admet-10	13	13	issued	issue	VERB
admet-10	13	14	guidance	guidance	NOUN
admet-10	13	15	on	on	ADP
admet-10	13	16	estimating	estimate	VERB
admet-10	13	17	the	the	DET
admet-10	13	18	maximum	maximum	ADJ
admet-10	13	19	safe	safe	ADJ
admet-10	13	20	starting	starting	NOUN
admet-10	13	21	dose	dose	VERB
admet-10	13	22	in	in	ADP
admet-10	13	23	initial	initial	ADJ
admet-10	13	24	clinical	clinical	ADJ
admet-10	13	25	trials	trial	NOUN
admet-10	13	26	for	for	ADP
admet-10	13	27	therapeutics	therapeutic	NOUN
admet-10	13	28	in	in	ADP
admet-10	13	29	adult	adult	NOUN
admet-10	13	30	healthy	healthy	ADJ
admet-10	13	31	volunteers	volunteer	NOUN
admet-10	13	32	,	,	PUNCT
admet-10	13	33	which	which	PRON
admet-10	13	34	provided	provide	VERB
admet-10	13	35	a	a	DET
admet-10	13	36	framework	framework	NOUN
admet-10	13	37	to	to	PART
admet-10	13	38	carry	carry	VERB
admet-10	13	39	out	out	ADP
admet-10	13	40	the	the	DET
admet-10	13	41	estimation	estimation	NOUN
admet-10	13	42	[	[	X
admet-10	13	43	3	3	NUM
admet-10	13	44	]	]	PUNCT
admet-10	13	45	.	.	PUNCT
admet-10	14	1	typically	typically	ADV
admet-10	14	2	this	this	PRON
admet-10	14	3	involves	involve	VERB
admet-10	14	4	the	the	DET
admet-10	14	5	use	use	NOUN
admet-10	14	6	of	of	ADP
admet-10	14	7	the	the	DET
admet-10	14	8	no	no	DET
admet-10	14	9	observed	observed	ADJ
admet-10	14	10	adverse	adverse	ADJ
admet-10	14	11	effect	effect	NOUN
admet-10	14	12	level	level	NOUN
admet-10	14	13	(	(	PUNCT
admet-10	14	14	noael	noael	PROPN
admet-10	14	15	)	)	PUNCT
admet-10	14	16	obtained	obtain	VERB
admet-10	14	17	from	from	ADP
admet-10	14	18	preclinical	preclinical	ADJ
admet-10	14	19	toxicology	toxicology	NOUN
admet-10	14	20	studies	study	NOUN
admet-10	14	21	,	,	PUNCT
admet-10	14	22	which	which	PRON
admet-10	14	23	is	be	AUX
admet-10	14	24	then	then	ADV
admet-10	14	25	converted	convert	VERB
admet-10	14	26	into	into	ADP
admet-10	14	27	a	a	DET
admet-10	14	28	human	human	ADJ
admet-10	14	29	equivalent	equivalent	NOUN
admet-10	14	30	dose	dose	NOUN
admet-10	14	31	(	(	PUNCT
admet-10	14	32	he	he	PRON
admet-10	14	33	d	d	VERB
admet-10	14	34	)	)	PUNCT
admet-10	14	35	from	from	ADP
admet-10	14	36	which	which	PRON
admet-10	14	37	a	a	DET
admet-10	14	38	safety	safety	NOUN
admet-10	14	39	factor	factor	NOUN
admet-10	14	40	is	be	AUX
admet-10	14	41	applied	apply	VERB
admet-10	14	42	to	to	PART
admet-10	14	43	derive	derive	VERB
admet-10	14	44	the	the	DET
admet-10	14	45	maximum	maximum	ADJ
admet-10	14	46	recommended	recommend	VERB
admet-10	14	47	start	start	NOUN
admet-10	14	48	dose	dose	PROPN
admet-10	14	49	(	(	PUNCT
admet-10	14	50	mrsd	mrsd	ADJ
admet-10	14	51	)	)	PUNCT
admet-10	14	52	.	.	PUNCT
admet-10	15	1	http://www.pub.iapchem.org/ojs/index.php/admet/index	http://www.pub.iapchem.org/ojs/index.php/admet/index	PROPN
admet-10	15	2	mailto:kintam@umac.mo	mailto:kintam@umac.mo	VERB
admet-10	15	3	tam	tam	PROPN
admet-10	15	4	admet	admet	PROPN
admet-10	15	5	&	&	CCONJ
admet-10	15	6	dmpk	dmpk	PROPN
admet-10	15	7	1(4	1(4	NUM
admet-10	15	8	)	)	PUNCT
admet-10	15	9	(	(	PUNCT
admet-10	15	10	2013	2013	NUM
admet-10	15	11	)	)	PUNCT
admet-10	15	12	63	63	NUM
admet-10	15	13	-	-	SYM
admet-10	15	14	75	75	NUM
admet-10	15	15	64	64	NUM
admet-10	15	16	the	the	DET
admet-10	15	17	noael	noael	PROPN
admet-10	15	18	method	method	NOUN
admet-10	15	19	is	be	AUX
admet-10	15	20	based	base	VERB
admet-10	15	21	on	on	ADP
admet-10	15	22	selecting	select	VERB
admet-10	15	23	a	a	DET
admet-10	15	24	dose	dose	NOUN
admet-10	15	25	with	with	ADP
admet-10	15	26	minimal	minimal	ADJ
admet-10	15	27	risk	risk	NOUN
admet-10	15	28	of	of	ADP
admet-10	15	29	toxicity	toxicity	NOUN
admet-10	15	30	,	,	PUNCT
admet-10	15	31	rather	rather	ADV
admet-10	15	32	than	than	ADP
admet-10	15	33	selecting	select	VERB
admet-10	15	34	one	one	NUM
admet-10	15	35	with	with	ADP
admet-10	15	36	minimal	minimal	ADJ
admet-10	15	37	pharmacology	pharmacology	NOUN
admet-10	15	38	activity	activity	NOUN
admet-10	15	39	in	in	ADP
admet-10	15	40	humans	human	NOUN
admet-10	15	41	.	.	PUNCT
admet-10	16	1	the	the	DET
admet-10	16	2	approach	approach	NOUN
admet-10	16	3	appears	appear	VERB
admet-10	16	4	to	to	PART
admet-10	16	5	work	work	VERB
admet-10	16	6	well	well	ADV
admet-10	16	7	with	with	ADP
admet-10	16	8	new	new	ADJ
admet-10	16	9	molecules	molecule	NOUN
admet-10	16	10	that	that	PRON
admet-10	16	11	act	act	VERB
admet-10	16	12	on	on	ADP
admet-10	16	13	established	establish	VERB
admet-10	16	14	targets	target	NOUN
admet-10	16	15	and/or	and/or	CCONJ
admet-10	16	16	have	have	VERB
admet-10	16	17	pharmacology	pharmacology	NOUN
admet-10	16	18	that	that	PRON
admet-10	16	19	is	be	AUX
admet-10	16	20	more	more	ADV
admet-10	16	21	or	or	CCONJ
admet-10	16	22	less	less	ADV
admet-10	16	23	understood	understand	VERB
admet-10	16	24	.	.	PUNCT
admet-10	17	1	however	however	ADV
admet-10	17	2	,	,	PUNCT
admet-10	17	3	the	the	DET
admet-10	17	4	life	life	NOUN
admet-10	17	5	-	-	PUNCT
admet-10	17	6	threatening	threaten	VERB
admet-10	17	7	adverse	adverse	ADJ
admet-10	17	8	events	event	NOUN
admet-10	17	9	that	that	PRON
admet-10	17	10	occurred	occur	VERB
admet-10	17	11	in	in	ADP
admet-10	17	12	2006	2006	NUM
admet-10	17	13	after	after	SCONJ
admet-10	17	14	the	the	DET
admet-10	17	15	fih	fih	NOUN
admet-10	17	16	administration	administration	NOUN
admet-10	17	17	of	of	ADP
admet-10	17	18	tng1412	tng1412	NOUN
admet-10	17	19	(	(	PUNCT
admet-10	17	20	a	a	DET
admet-10	17	21	novel	novel	NOUN
admet-10	17	22	cd28	cd28	PROPN
admet-10	17	23	super	super	ADJ
admet-10	17	24	-	-	ADJ
admet-10	17	25	agonist	agonist	ADJ
admet-10	17	26	antibody	antibody	NOUN
admet-10	17	27	)	)	PUNCT
admet-10	17	28	was	be	AUX
admet-10	17	29	a	a	DET
admet-10	17	30	wake	wake	VERB
admet-10	17	31	-	-	PUNCT
admet-10	17	32	up	up	ADP
admet-10	17	33	call	call	NOUN
admet-10	17	34	to	to	ADP
admet-10	17	35	the	the	DET
admet-10	17	36	industry	industry	NOUN
admet-10	17	37	,	,	PUNCT
admet-10	17	38	and	and	CCONJ
admet-10	17	39	led	lead	VERB
admet-10	17	40	to	to	ADP
admet-10	17	41	immediate	immediate	ADJ
admet-10	17	42	reactions	reaction	NOUN
admet-10	17	43	from	from	ADP
admet-10	17	44	different	different	ADJ
admet-10	17	45	regulators	regulator	NOUN
admet-10	18	1	[	[	X
admet-10	18	2	4	4	NUM
admet-10	18	3	]	]	PUNCT
admet-10	18	4	.	.	PUNCT
admet-10	19	1	subsequently	subsequently	ADV
admet-10	19	2	,	,	PUNCT
admet-10	19	3	the	the	DET
admet-10	19	4	european	european	PROPN
admet-10	19	5	medicines	medicines	PROPN
admet-10	19	6	agency	agency	PROPN
admet-10	19	7	(	(	PUNCT
admet-10	19	8	emea	emea	PROPN
admet-10	19	9	)	)	PUNCT
admet-10	19	10	has	have	AUX
admet-10	19	11	issued	issue	VERB
admet-10	19	12	new	new	ADJ
admet-10	19	13	guidance	guidance	NOUN
admet-10	19	14	[	[	X
admet-10	19	15	5	5	NUM
admet-10	19	16	]	]	PUNCT
admet-10	19	17	,	,	PUNCT
admet-10	19	18	which	which	PRON
admet-10	19	19	underlines	underline	VERB
admet-10	19	20	the	the	DET
admet-10	19	21	need	need	NOUN
admet-10	19	22	to	to	PART
admet-10	19	23	better	well	ADV
admet-10	19	24	mitigate	mitigate	VERB
admet-10	19	25	the	the	DET
admet-10	19	26	risk	risk	NOUN
admet-10	19	27	regarding	regard	VERB
admet-10	19	28	fih	fih	NOUN
admet-10	19	29	dosing	dose	VERB
admet-10	19	30	,	,	PUNCT
admet-10	19	31	and	and	CCONJ
admet-10	19	32	proposes	propose	VERB
admet-10	19	33	an	an	DET
admet-10	19	34	improved	improved	ADJ
admet-10	19	35	approach	approach	NOUN
admet-10	19	36	to	to	PART
admet-10	19	37	dose	dose	VERB
admet-10	19	38	selection	selection	NOUN
admet-10	19	39	through	through	ADP
admet-10	19	40	the	the	DET
admet-10	19	41	combined	combine	VERB
admet-10	19	42	analysis	analysis	NOUN
admet-10	19	43	of	of	ADP
admet-10	19	44	all	all	PRON
admet-10	19	45	of	of	ADP
admet-10	19	46	the	the	DET
admet-10	19	47	pharmacology	pharmacology	NOUN
admet-10	19	48	,	,	PUNCT
admet-10	19	49	safety	safety	NOUN
admet-10	19	50	and	and	CCONJ
admet-10	19	51	efficacy	efficacy	NOUN
admet-10	19	52	preclinical	preclinical	ADJ
admet-10	19	53	data	datum	NOUN
admet-10	19	54	.	.	PUNCT
admet-10	20	1	one	one	NUM
admet-10	20	2	of	of	ADP
admet-10	20	3	the	the	DET
admet-10	20	4	main	main	ADJ
admet-10	20	5	objectives	objective	NOUN
admet-10	20	6	of	of	ADP
admet-10	20	7	the	the	DET
admet-10	20	8	new	new	ADJ
admet-10	20	9	process	process	NOUN
admet-10	20	10	is	be	AUX
admet-10	20	11	to	to	PART
admet-10	20	12	define	define	VERB
admet-10	20	13	a	a	DET
admet-10	20	14	starting	starting	NOUN
admet-10	20	15	dose	dose	NOUN
admet-10	20	16	that	that	PRON
admet-10	20	17	is	be	AUX
admet-10	20	18	expected	expect	VERB
admet-10	20	19	to	to	PART
admet-10	20	20	result	result	VERB
admet-10	20	21	in	in	ADP
admet-10	20	22	a	a	DET
admet-10	20	23	minimum	minimum	ADJ
admet-10	20	24	anticipated	anticipate	VERB
admet-10	20	25	biological	biological	ADJ
admet-10	20	26	effect	effect	NOUN
admet-10	20	27	level	level	NOUN
admet-10	20	28	(	(	PUNCT
admet-10	20	29	mabel	mabel	PROPN
admet-10	20	30	)	)	PUNCT
admet-10	20	31	,	,	PUNCT
admet-10	20	32	particularly	particularly	ADV
admet-10	20	33	for	for	ADP
admet-10	20	34	investigational	investigational	ADJ
admet-10	20	35	medicinal	medicinal	ADJ
admet-10	20	36	products	product	NOUN
admet-10	20	37	where	where	SCONJ
admet-10	20	38	risk	risk	NOUN
admet-10	20	39	factors	factor	NOUN
admet-10	20	40	were	be	AUX
admet-10	20	41	identified	identify	VERB
admet-10	20	42	in	in	ADP
admet-10	20	43	(	(	PUNCT
admet-10	20	44	1	1	NUM
admet-10	20	45	)	)	PUNCT
admet-10	20	46	mode	mode	NOUN
admet-10	20	47	of	of	ADP
admet-10	20	48	action	action	NOUN
admet-10	20	49	,	,	PUNCT
admet-10	20	50	(	(	PUNCT
admet-10	20	51	2	2	X
admet-10	20	52	)	)	PUNCT
admet-10	20	53	nature	nature	NOUN
admet-10	20	54	of	of	ADP
admet-10	20	55	the	the	DET
admet-10	20	56	target	target	NOUN
admet-10	20	57	and	and	CCONJ
admet-10	20	58	(	(	PUNCT
admet-10	20	59	3	3	X
admet-10	20	60	)	)	PUNCT
admet-10	20	61	relevance	relevance	NOUN
admet-10	20	62	of	of	ADP
admet-10	20	63	animal	animal	NOUN
admet-10	20	64	species	specie	NOUN
admet-10	20	65	and	and	CCONJ
admet-10	20	66	models	model	NOUN
admet-10	20	67	.	.	PUNCT
admet-10	21	1	with	with	ADP
admet-10	21	2	regard	regard	NOUN
admet-10	21	3	to	to	ADP
admet-10	21	4	oncology	oncology	NOUN
admet-10	21	5	drugs	drug	NOUN
admet-10	21	6	,	,	PUNCT
admet-10	21	7	they	they	PRON
admet-10	21	8	are	be	AUX
admet-10	21	9	somewhat	somewhat	ADV
admet-10	21	10	different	different	ADJ
admet-10	21	11	from	from	ADP
admet-10	21	12	other	other	ADJ
admet-10	21	13	therapeutic	therapeutic	ADJ
admet-10	21	14	agents	agent	NOUN
admet-10	21	15	in	in	ADP
admet-10	21	16	terms	term	NOUN
admet-10	21	17	of	of	ADP
admet-10	21	18	clinical	clinical	ADJ
admet-10	21	19	evaluations	evaluation	NOUN
admet-10	21	20	and	and	CCONJ
admet-10	21	21	estimating	estimate	VERB
admet-10	21	22	the	the	DET
admet-10	21	23	fih	fih	NOUN
admet-10	21	24	dose	dose	NOUN
admet-10	21	25	.	.	PUNCT
admet-10	22	1	for	for	ADP
admet-10	22	2	example	example	NOUN
admet-10	22	3	,	,	PUNCT
admet-10	22	4	the	the	DET
admet-10	22	5	fih	fih	NOUN
admet-10	22	6	clinical	clinical	ADJ
admet-10	22	7	studies	study	NOUN
admet-10	22	8	for	for	ADP
admet-10	22	9	traditional	traditional	ADJ
admet-10	22	10	cytotoxic	cytotoxic	ADJ
admet-10	22	11	agents	agent	NOUN
admet-10	22	12	are	be	AUX
admet-10	22	13	usually	usually	ADV
admet-10	22	14	carried	carry	VERB
admet-10	22	15	out	out	ADP
admet-10	22	16	in	in	ADP
admet-10	22	17	patients	patient	NOUN
admet-10	22	18	with	with	ADP
admet-10	22	19	treatment	treatment	NOUN
admet-10	22	20	-	-	PUNCT
admet-10	22	21	refractory	refractory	NOUN
admet-10	22	22	cancer	cancer	NOUN
admet-10	22	23	instead	instead	ADV
admet-10	22	24	of	of	ADP
admet-10	22	25	healthy	healthy	ADJ
admet-10	22	26	volunteers	volunteer	NOUN
admet-10	22	27	.	.	PUNCT
admet-10	23	1	in	in	ADP
admet-10	23	2	these	these	DET
admet-10	23	3	instances	instance	NOUN
admet-10	23	4	,	,	PUNCT
admet-10	23	5	there	there	PRON
admet-10	23	6	is	be	VERB
admet-10	23	7	always	always	ADV
admet-10	23	8	a	a	DET
admet-10	23	9	hope	hope	NOUN
admet-10	23	10	for	for	ADP
admet-10	23	11	a	a	DET
admet-10	23	12	therapeutic	therapeutic	ADJ
admet-10	23	13	benefit	benefit	NOUN
admet-10	23	14	and	and	CCONJ
admet-10	23	15	a	a	DET
admet-10	23	16	desire	desire	NOUN
admet-10	23	17	to	to	PART
admet-10	23	18	minimise	minimise	VERB
admet-10	23	19	patient	patient	ADJ
admet-10	23	20	exposure	exposure	NOUN
admet-10	23	21	to	to	ADP
admet-10	23	22	sub	sub	ADJ
admet-10	23	23	-	-	ADJ
admet-10	23	24	therapeutic	therapeutic	ADJ
admet-10	23	25	doses	dose	NOUN
admet-10	23	26	.	.	PUNCT
admet-10	24	1	the	the	DET
admet-10	24	2	initial	initial	ADJ
admet-10	24	3	dose	dose	NOUN
admet-10	24	4	selection	selection	NOUN
admet-10	24	5	is	be	AUX
admet-10	24	6	usually	usually	ADV
admet-10	24	7	based	base	VERB
admet-10	24	8	on	on	ADP
admet-10	24	9	the	the	DET
admet-10	24	10	lethal	lethal	ADJ
admet-10	24	11	dose	dose	NOUN
admet-10	24	12	in	in	ADP
admet-10	24	13	10	10	NUM
admet-10	24	14	%	%	NOUN
admet-10	24	15	of	of	ADP
admet-10	24	16	animals	animal	NOUN
admet-10	24	17	(	(	PUNCT
admet-10	24	18	ld10	ld10	PROPN
admet-10	24	19	)	)	PUNCT
admet-10	25	1	[	[	X
admet-10	25	2	6	6	NUM
admet-10	25	3	]	]	PUNCT
admet-10	25	4	.	.	PUNCT
admet-10	26	1	there	there	PRON
admet-10	26	2	are	be	VERB
admet-10	26	3	additional	additional	ADJ
admet-10	26	4	considerations	consideration	NOUN
admet-10	26	5	in	in	ADP
admet-10	26	6	the	the	DET
admet-10	26	7	design	design	NOUN
admet-10	26	8	of	of	ADP
admet-10	26	9	fih	fih	NOUN
admet-10	26	10	dose	dose	VERB
admet-10	26	11	for	for	ADP
admet-10	26	12	molecular	molecular	ADJ
admet-10	26	13	targeted	target	VERB
admet-10	26	14	anticancer	anticancer	NOUN
admet-10	26	15	compounds	compound	NOUN
admet-10	26	16	.	.	PUNCT
admet-10	27	1	in	in	ADP
admet-10	27	2	this	this	DET
admet-10	27	3	article	article	NOUN
admet-10	27	4	,	,	PUNCT
admet-10	27	5	we	we	PRON
admet-10	27	6	will	will	AUX
admet-10	27	7	first	first	ADV
admet-10	27	8	discuss	discuss	VERB
admet-10	27	9	the	the	DET
admet-10	27	10	general	general	ADJ
admet-10	27	11	considerations	consideration	NOUN
admet-10	27	12	on	on	ADP
admet-10	27	13	fih	fih	NOUN
admet-10	27	14	dose	dose	VERB
admet-10	27	15	in	in	ADP
admet-10	27	16	the	the	DET
admet-10	27	17	context	context	NOUN
admet-10	27	18	of	of	ADP
admet-10	27	19	clinical	clinical	ADJ
admet-10	27	20	trials	trial	NOUN
admet-10	27	21	.	.	PUNCT
admet-10	28	1	then	then	ADV
admet-10	28	2	,	,	PUNCT
admet-10	28	3	we	we	PRON
admet-10	28	4	will	will	AUX
admet-10	28	5	briefly	briefly	ADV
admet-10	28	6	outline	outline	VERB
admet-10	28	7	the	the	DET
admet-10	28	8	noael	noael	PROPN
admet-10	28	9	and	and	CCONJ
admet-10	28	10	the	the	DET
admet-10	28	11	mabel	mabel	NOUN
admet-10	28	12	approaches	approach	VERB
admet-10	28	13	for	for	ADP
admet-10	28	14	the	the	DET
admet-10	28	15	estimations	estimation	NOUN
admet-10	28	16	of	of	ADP
admet-10	28	17	fih	fih	NOUN
admet-10	28	18	dose	dose	PROPN
admet-10	28	19	.	.	PUNCT
admet-10	29	1	particular	particular	ADJ
admet-10	29	2	attention	attention	NOUN
admet-10	29	3	will	will	AUX
admet-10	29	4	be	be	AUX
admet-10	29	5	placed	place	VERB
admet-10	29	6	on	on	ADP
admet-10	29	7	the	the	DET
admet-10	29	8	development	development	NOUN
admet-10	29	9	of	of	ADP
admet-10	29	10	fih	fih	NOUN
admet-10	29	11	dose	dose	NOUN
admet-10	29	12	for	for	ADP
admet-10	29	13	oncology	oncology	NOUN
admet-10	29	14	drugs	drug	NOUN
admet-10	29	15	.	.	PUNCT
admet-10	30	1	2	2	X
admet-10	30	2	.	.	X
admet-10	30	3	entering	enter	VERB
admet-10	30	4	the	the	DET
admet-10	30	5	clinics	clinic	NOUN
admet-10	30	6	the	the	DET
admet-10	30	7	main	main	ADJ
admet-10	30	8	goal	goal	NOUN
admet-10	30	9	of	of	ADP
admet-10	30	10	clinical	clinical	ADJ
admet-10	30	11	trials	trial	NOUN
admet-10	30	12	is	be	AUX
admet-10	30	13	to	to	PART
admet-10	30	14	evaluate	evaluate	VERB
admet-10	30	15	whether	whether	SCONJ
admet-10	30	16	the	the	DET
admet-10	30	17	treatment	treatment	NOUN
admet-10	30	18	is	be	AUX
admet-10	30	19	effective	effective	ADJ
admet-10	30	20	and	and	CCONJ
admet-10	30	21	safe	safe	ADJ
admet-10	30	22	in	in	ADP
admet-10	30	23	humans	human	NOUN
admet-10	30	24	.	.	PUNCT
admet-10	31	1	before	before	SCONJ
admet-10	31	2	an	an	DET
admet-10	31	3	investigational	investigational	ADJ
admet-10	31	4	new	new	ADJ
admet-10	31	5	drug	drug	NOUN
admet-10	31	6	(	(	PUNCT
admet-10	31	7	ind	ind	NOUN
admet-10	31	8	)	)	PUNCT
admet-10	31	9	can	can	AUX
admet-10	31	10	be	be	AUX
admet-10	31	11	given	give	VERB
admet-10	31	12	to	to	ADP
admet-10	31	13	humans	human	NOUN
admet-10	31	14	,	,	PUNCT
admet-10	31	15	it	it	PRON
admet-10	31	16	must	must	AUX
admet-10	31	17	be	be	AUX
admet-10	31	18	tested	test	VERB
admet-10	31	19	thoroughly	thoroughly	ADV
admet-10	31	20	in	in	ADP
admet-10	31	21	animals	animal	NOUN
admet-10	31	22	to	to	PART
admet-10	31	23	find	find	VERB
admet-10	31	24	out	out	ADP
admet-10	31	25	the	the	DET
admet-10	31	26	following	following	NOUN
admet-10	31	27	[	[	X
admet-10	31	28	7	7	NUM
admet-10	31	29	]	]	NUM
admet-10	31	30	:	:	PUNCT
admet-10	31	31	(	(	PUNCT
admet-10	31	32	1	1	X
admet-10	31	33	)	)	PUNCT
admet-10	31	34	the	the	DET
admet-10	31	35	effects	effect	NOUN
admet-10	31	36	in	in	ADP
admet-10	31	37	the	the	DET
admet-10	31	38	body	body	NOUN
admet-10	31	39	systems	system	NOUN
admet-10	31	40	(	(	PUNCT
admet-10	31	41	pharmacodynamics	pharmacodynamic	NOUN
admet-10	31	42	(	(	PUNCT
admet-10	31	43	pd	pd	NOUN
admet-10	31	44	)	)	PUNCT
admet-10	31	45	)	)	PUNCT
admet-10	31	46	,	,	PUNCT
admet-10	31	47	(	(	PUNCT
admet-10	31	48	2	2	X
admet-10	31	49	)	)	PUNCT
admet-10	31	50	the	the	DET
admet-10	31	51	blood	blood	NOUN
admet-10	31	52	levels	level	NOUN
admet-10	31	53	and	and	CCONJ
admet-10	31	54	how	how	SCONJ
admet-10	31	55	it	it	PRON
admet-10	31	56	is	be	AUX
admet-10	31	57	absorbed	absorb	VERB
admet-10	31	58	,	,	PUNCT
admet-10	31	59	distributed	distribute	VERB
admet-10	31	60	,	,	PUNCT
admet-10	31	61	metabolised	metabolise	VERB
admet-10	31	62	and	and	CCONJ
admet-10	31	63	eliminated	eliminate	VERB
admet-10	31	64	after	after	ADP
admet-10	31	65	dosing	dose	VERB
admet-10	31	66	(	(	PUNCT
admet-10	31	67	pharmacokinetics	pharmacokinetic	NOUN
admet-10	31	68	(	(	PUNCT
admet-10	31	69	pk	pk	NOUN
admet-10	31	70	)	)	PUNCT
admet-10	31	71	)	)	PUNCT
admet-10	31	72	,	,	PUNCT
admet-10	31	73	(	(	PUNCT
admet-10	31	74	3	3	X
admet-10	31	75	)	)	PUNCT
admet-10	31	76	a	a	DET
admet-10	31	77	range	range	NOUN
admet-10	31	78	of	of	ADP
admet-10	31	79	doses	dose	NOUN
admet-10	31	80	of	of	ADP
admet-10	31	81	the	the	DET
admet-10	31	82	ind	ind	NOUN
admet-10	31	83	,	,	PUNCT
admet-10	31	84	up	up	ADP
admet-10	31	85	to	to	ADP
admet-10	31	86	a	a	DET
admet-10	31	87	toxic	toxic	ADJ
admet-10	31	88	level	level	NOUN
admet-10	31	89	,	,	PUNCT
admet-10	31	90	the	the	DET
admet-10	31	91	organ	organ	NOUN
admet-10	31	92	toxicity	toxicity	NOUN
admet-10	31	93	,	,	PUNCT
admet-10	31	94	and	and	CCONJ
admet-10	31	95	safety	safety	NOUN
admet-10	31	96	margin	margin	NOUN
admet-10	31	97	in	in	ADP
admet-10	31	98	terms	term	NOUN
admet-10	31	99	of	of	ADP
admet-10	31	100	the	the	DET
admet-10	31	101	noael	noael	PROPN
admet-10	31	102	.	.	PUNCT
admet-10	32	1	after	after	ADP
admet-10	32	2	the	the	DET
admet-10	32	3	preclinical	preclinical	ADJ
admet-10	32	4	studies	study	NOUN
admet-10	32	5	,	,	PUNCT
admet-10	32	6	there	there	PRON
admet-10	32	7	are	be	VERB
admet-10	32	8	four	four	NUM
admet-10	32	9	phases	phase	NOUN
admet-10	32	10	of	of	ADP
admet-10	32	11	trials	trial	NOUN
admet-10	32	12	in	in	ADP
admet-10	32	13	humans	human	NOUN
admet-10	32	14	,	,	PUNCT
admet-10	32	15	which	which	PRON
admet-10	32	16	sometimes	sometimes	ADV
admet-10	32	17	overlap	overlap	VERB
admet-10	32	18	in	in	ADP
admet-10	32	19	practice	practice	NOUN
admet-10	32	20	.	.	PUNCT
admet-10	33	1	phases	phase	NOUN
admet-10	33	2	1	1	NUM
admet-10	33	3	to	to	PART
admet-10	33	4	3	3	NUM
admet-10	33	5	are	be	AUX
admet-10	33	6	performed	perform	VERB
admet-10	33	7	before	before	SCONJ
admet-10	33	8	a	a	DET
admet-10	33	9	licence	licence	NOUN
admet-10	33	10	is	be	AUX
admet-10	33	11	granted	grant	VERB
admet-10	33	12	,	,	PUNCT
admet-10	33	13	while	while	SCONJ
admet-10	33	14	phase	phase	NOUN
admet-10	33	15	4	4	NUM
admet-10	33	16	is	be	AUX
admet-10	33	17	launched	launch	VERB
admet-10	33	18	after	after	ADP
admet-10	33	19	authorisation	authorisation	NOUN
admet-10	34	1	[	[	X
admet-10	34	2	8	8	NUM
admet-10	34	3	]	]	PUNCT
admet-10	34	4	.	.	PUNCT
admet-10	35	1	table	table	NOUN
admet-10	35	2	1	1	NUM
admet-10	35	3	summarises	summarise	NOUN
admet-10	35	4	the	the	DET
admet-10	35	5	four	four	NUM
admet-10	35	6	clinical	clinical	ADJ
admet-10	35	7	phases	phase	NOUN
admet-10	35	8	of	of	ADP
admet-10	35	9	the	the	DET
admet-10	35	10	development	development	NOUN
admet-10	35	11	of	of	ADP
admet-10	35	12	a	a	DET
admet-10	35	13	typical	typical	ADJ
admet-10	35	14	drug	drug	NOUN
admet-10	35	15	.	.	PUNCT
admet-10	36	1	admet	admet	PROPN
admet-10	36	2	&	&	CCONJ
admet-10	36	3	dmpk	dmpk	PROPN
admet-10	36	4	1(4	1(4	NUM
admet-10	36	5	)	)	PUNCT
admet-10	36	6	(	(	PUNCT
admet-10	36	7	2013	2013	NUM
admet-10	36	8	)	)	PUNCT
admet-10	36	9	63	63	NUM
admet-10	36	10	-	-	SYM
admet-10	36	11	75	75	NUM
admet-10	36	12	estimating	estimate	VERB
admet-10	36	13	first	first	ADV
admet-10	36	14	in	in	ADP
admet-10	36	15	human	human	PROPN
admet-10	36	16	dose	dose	NOUN
admet-10	36	17	doi	doi	PROPN
admet-10	36	18	:	:	PUNCT
admet-10	36	19	10.5599	10.5599	NUM
admet-10	36	20	/	/	SYM
admet-10	36	21	admet.1.4.10	admet.1.4.10	ADJ
admet-10	36	22	65	65	NUM
admet-10	36	23	table	table	NOUN
admet-10	36	24	1	1	NUM
admet-10	36	25	.	.	PUNCT
admet-10	37	1	summary	summary	NOUN
admet-10	37	2	of	of	ADP
admet-10	37	3	the	the	DET
admet-10	37	4	four	four	NUM
admet-10	37	5	clinical	clinical	ADJ
admet-10	37	6	phases	phase	NOUN
admet-10	37	7	of	of	ADP
admet-10	37	8	development	development	NOUN
admet-10	37	9	of	of	ADP
admet-10	37	10	a	a	DET
admet-10	37	11	typical	typical	ADJ
admet-10	37	12	drug	drug	NOUN
admet-10	37	13	*	*	PUNCT
admet-10	37	14	phase	phase	NOUN
admet-10	37	15	typical	typical	ADJ
admet-10	37	16	number	number	NOUN
admet-10	37	17	and	and	CCONJ
admet-10	37	18	type	type	NOUN
admet-10	37	19	of	of	ADP
admet-10	37	20	subjects	subject	NOUN
admet-10	37	21	objectives	objective	VERB
admet-10	37	22	1	1	NUM
admet-10	37	23	20	20	NUM
admet-10	37	24	–	–	PUNCT
admet-10	37	25	200	200	NUM
admet-10	37	26	healthy	healthy	ADJ
admet-10	37	27	subjects	subject	NOUN
admet-10	37	28	(	(	PUNCT
admet-10	37	29	usually	usually	ADV
admet-10	37	30	)	)	PUNCT
admet-10	37	31	or	or	CCONJ
admet-10	37	32	patients	patient	NOUN
admet-10	37	33	who	who	PRON
admet-10	37	34	are	be	AUX
admet-10	37	35	not	not	PART
admet-10	37	36	expected	expect	VERB
admet-10	37	37	to	to	PART
admet-10	37	38	benefit	benefit	VERB
admet-10	37	39	from	from	ADP
admet-10	37	40	the	the	DET
admet-10	37	41	ind	ind	NOUN
admet-10	37	42	determine	determine	VERB
admet-10	37	43	how	how	SCONJ
admet-10	37	44	well	well	ADV
admet-10	37	45	the	the	DET
admet-10	37	46	ind	ind	NOUN
admet-10	37	47	can	can	AUX
admet-10	37	48	be	be	AUX
admet-10	37	49	tolerated	tolerate	VERB
admet-10	37	50	in	in	ADP
admet-10	37	51	humans	human	NOUN
admet-10	37	52	,	,	PUNCT
admet-10	37	53	study	study	VERB
admet-10	37	54	the	the	DET
admet-10	37	55	clinical	clinical	ADJ
admet-10	37	56	pharmacology	pharmacology	NOUN
admet-10	37	57	and	and	CCONJ
admet-10	37	58	toxicity	toxicity	NOUN
admet-10	37	59	and	and	CCONJ
admet-10	37	60	find	find	VERB
admet-10	37	61	the	the	DET
admet-10	37	62	maximum	maximum	ADV
admet-10	37	63	-	-	PUNCT
admet-10	37	64	tolerated	tolerate	VERB
admet-10	37	65	dose	dose	NOUN
admet-10	37	66	to	to	PART
admet-10	37	67	aid	aid	VERB
admet-10	37	68	the	the	DET
admet-10	37	69	selection	selection	NOUN
admet-10	37	70	of	of	ADP
admet-10	37	71	dose	dose	NOUN
admet-10	37	72	and/or	and/or	CCONJ
admet-10	37	73	schedule	schedule	NOUN
admet-10	37	74	for	for	ADP
admet-10	37	75	phase	phase	NOUN
admet-10	37	76	2	2	NUM
admet-10	37	77	2	2	NUM
admet-10	37	78	100	100	NUM
admet-10	37	79	-	-	SYM
admet-10	37	80	400	400	NUM
admet-10	37	81	patients	patient	NOUN
admet-10	37	82	with	with	ADP
admet-10	37	83	the	the	DET
admet-10	37	84	target	target	NOUN
admet-10	37	85	disease	disease	NOUN
admet-10	37	86	examine	examine	VERB
admet-10	37	87	dose	dose	PROPN
admet-10	37	88	–	–	PUNCT
admet-10	37	89	response	response	NOUN
admet-10	37	90	curves	curve	NOUN
admet-10	37	91	in	in	ADP
admet-10	37	92	patients	patient	NOUN
admet-10	37	93	,	,	PUNCT
admet-10	37	94	and	and	CCONJ
admet-10	37	95	evaluate	evaluate	VERB
admet-10	37	96	the	the	DET
admet-10	37	97	clinical	clinical	ADJ
admet-10	37	98	benefits	benefit	NOUN
admet-10	37	99	that	that	PRON
admet-10	37	100	might	might	AUX
admet-10	37	101	be	be	AUX
admet-10	37	102	seen	see	VERB
admet-10	37	103	in	in	ADP
admet-10	37	104	a	a	DET
admet-10	37	105	small	small	ADJ
admet-10	37	106	group	group	NOUN
admet-10	37	107	of	of	ADP
admet-10	37	108	patients	patient	NOUN
admet-10	37	109	3	3	NUM
admet-10	37	110	1000	1000	NUM
admet-10	37	111	-	-	SYM
admet-10	37	112	5000	5000	NUM
admet-10	37	113	patients	patient	NOUN
admet-10	37	114	with	with	ADP
admet-10	37	115	the	the	DET
admet-10	37	116	target	target	NOUN
admet-10	37	117	disease	disease	NOUN
admet-10	37	118	test	test	NOUN
admet-10	37	119	in	in	ADP
admet-10	37	120	a	a	DET
admet-10	37	121	controlled	control	VERB
admet-10	37	122	fashion	fashion	NOUN
admet-10	37	123	in	in	ADP
admet-10	37	124	a	a	DET
admet-10	37	125	large	large	ADJ
admet-10	37	126	patient	patient	ADJ
admet-10	37	127	population	population	NOUN
admet-10	37	128	against	against	ADP
admet-10	37	129	a	a	DET
admet-10	37	130	placebo	placebo	NOUN
admet-10	37	131	or	or	CCONJ
admet-10	37	132	standard	standard	ADJ
admet-10	37	133	therapy	therapy	NOUN
admet-10	37	134	with	with	ADP
admet-10	37	135	respect	respect	NOUN
admet-10	37	136	to	to	ADP
admet-10	37	137	safety	safety	NOUN
admet-10	37	138	and	and	CCONJ
admet-10	37	139	efficacy	efficacy	NOUN
admet-10	37	140	4	4	NUM
admet-10	37	141	many	many	ADJ
admet-10	37	142	thousands	thousand	NOUN
admet-10	37	143	of	of	ADP
admet-10	37	144	patients	patient	NOUN
admet-10	37	145	with	with	ADP
admet-10	37	146	the	the	DET
admet-10	37	147	target	target	NOUN
admet-10	37	148	disease	disease	NOUN
admet-10	37	149	post	post	ADJ
admet-10	37	150	-	-	ADJ
admet-10	37	151	marketing	marketing	ADJ
admet-10	37	152	study	study	NOUN
admet-10	37	153	to	to	PART
admet-10	37	154	gather	gather	VERB
admet-10	37	155	additional	additional	ADJ
admet-10	37	156	safety	safety	NOUN
admet-10	37	157	information	information	NOUN
admet-10	37	158	from	from	ADP
admet-10	37	159	a	a	DET
admet-10	37	160	larger	large	ADJ
admet-10	37	161	group	group	NOUN
admet-10	37	162	of	of	ADP
admet-10	37	163	patients	patient	NOUN
admet-10	37	164	in	in	ADP
admet-10	37	165	order	order	NOUN
admet-10	37	166	to	to	PART
admet-10	37	167	understand	understand	VERB
admet-10	37	168	the	the	DET
admet-10	37	169	long	long	ADJ
admet-10	37	170	-	-	PUNCT
admet-10	37	171	term	term	NOUN
admet-10	37	172	safety	safety	NOUN
admet-10	37	173	and	and	CCONJ
admet-10	37	174	monitor	monitor	VERB
admet-10	37	175	drug	drug	NOUN
admet-10	37	176	-	-	PUNCT
admet-10	37	177	drug	drug	NOUN
admet-10	37	178	interactions	interaction	NOUN
admet-10	37	179	*	*	PUNCT
admet-10	37	180	the	the	DET
admet-10	37	181	number	number	NOUN
admet-10	37	182	of	of	ADP
admet-10	37	183	subjects	subject	NOUN
admet-10	37	184	listed	list	VERB
admet-10	37	185	in	in	ADP
admet-10	37	186	the	the	DET
admet-10	37	187	table	table	NOUN
admet-10	37	188	were	be	AUX
admet-10	37	189	adopted	adopt	VERB
admet-10	37	190	from	from	ADP
admet-10	37	191	the	the	DET
admet-10	37	192	abpi	abpi	NOUN
admet-10	37	193	guidelines	guideline	NOUN
admet-10	37	194	[	[	X
admet-10	37	195	9	9	NUM
admet-10	37	196	]	]	PUNCT
admet-10	37	197	.	.	PUNCT
admet-10	38	1	it	it	PRON
admet-10	38	2	should	should	AUX
admet-10	38	3	be	be	AUX
admet-10	38	4	noted	note	VERB
admet-10	38	5	that	that	SCONJ
admet-10	38	6	these	these	DET
admet-10	38	7	values	value	NOUN
admet-10	38	8	could	could	AUX
admet-10	38	9	vary	vary	VERB
admet-10	38	10	,	,	PUNCT
admet-10	38	11	depending	depend	VERB
admet-10	38	12	on	on	ADP
admet-10	38	13	the	the	DET
admet-10	38	14	therapeutic	therapeutic	ADJ
admet-10	38	15	areas	area	NOUN
admet-10	38	16	,	,	PUNCT
admet-10	38	17	the	the	DET
admet-10	38	18	trial	trial	NOUN
admet-10	38	19	design	design	NOUN
admet-10	38	20	and	and	CCONJ
admet-10	38	21	the	the	DET
admet-10	38	22	clinical	clinical	ADJ
admet-10	38	23	questions	question	NOUN
admet-10	38	24	to	to	PART
admet-10	38	25	be	be	AUX
admet-10	38	26	addressed	address	VERB
admet-10	38	27	.	.	PUNCT
admet-10	39	1	for	for	ADP
admet-10	39	2	any	any	DET
admet-10	39	3	clinical	clinical	ADJ
admet-10	39	4	trial	trial	NOUN
admet-10	39	5	,	,	PUNCT
admet-10	39	6	the	the	DET
admet-10	39	7	number	number	NOUN
admet-10	39	8	of	of	ADP
admet-10	39	9	subjects	subject	NOUN
admet-10	39	10	has	have	VERB
admet-10	39	11	to	to	PART
admet-10	39	12	be	be	AUX
admet-10	39	13	planned	plan	VERB
admet-10	39	14	on	on	ADP
admet-10	39	15	a	a	DET
admet-10	39	16	justifiable	justifiable	ADJ
admet-10	39	17	and	and	CCONJ
admet-10	39	18	rational	rational	ADJ
admet-10	39	19	basis	basis	NOUN
admet-10	39	20	(	(	PUNCT
admet-10	39	21	see	see	VERB
admet-10	39	22	reference	reference	NOUN
admet-10	39	23	10	10	NUM
admet-10	39	24	for	for	ADP
admet-10	39	25	further	further	ADJ
admet-10	39	26	detail	detail	NOUN
admet-10	39	27	)	)	PUNCT
admet-10	39	28	.	.	PUNCT
admet-10	40	1	before	before	SCONJ
admet-10	40	2	an	an	DET
admet-10	40	3	ind	ind	NOUN
admet-10	40	4	enters	enter	VERB
admet-10	40	5	a	a	DET
admet-10	40	6	phase	phase	NOUN
admet-10	40	7	1	1	NUM
admet-10	40	8	trial	trial	NOUN
admet-10	40	9	,	,	PUNCT
admet-10	40	10	one	one	NUM
admet-10	40	11	of	of	ADP
admet-10	40	12	the	the	DET
admet-10	40	13	most	most	ADV
admet-10	40	14	important	important	ADJ
admet-10	40	15	tasks	task	NOUN
admet-10	40	16	is	be	AUX
admet-10	40	17	to	to	PART
admet-10	40	18	estimate	estimate	VERB
admet-10	40	19	a	a	DET
admet-10	40	20	starting	starting	NOUN
admet-10	40	21	dose	dose	NOUN
admet-10	40	22	that	that	PRON
admet-10	40	23	is	be	AUX
admet-10	40	24	low	low	ADJ
admet-10	40	25	enough	enough	ADV
admet-10	40	26	to	to	PART
admet-10	40	27	be	be	AUX
admet-10	40	28	safe	safe	ADJ
admet-10	40	29	in	in	ADP
admet-10	40	30	humans	human	NOUN
admet-10	40	31	,	,	PUNCT
admet-10	40	32	but	but	CCONJ
admet-10	40	33	not	not	PART
admet-10	40	34	so	so	ADV
admet-10	40	35	conservative	conservative	ADJ
admet-10	40	36	that	that	SCONJ
admet-10	40	37	excessively	excessively	ADV
admet-10	40	38	costly	costly	ADJ
admet-10	40	39	and	and	CCONJ
admet-10	40	40	time	time	NOUN
admet-10	40	41	-	-	PUNCT
admet-10	40	42	consuming	consume	VERB
admet-10	40	43	dose	dose	NOUN
admet-10	40	44	escalations	escalation	NOUN
admet-10	40	45	are	be	AUX
admet-10	40	46	needed	need	VERB
admet-10	40	47	.	.	PUNCT
admet-10	41	1	generally	generally	ADV
admet-10	41	2	,	,	PUNCT
admet-10	41	3	the	the	DET
admet-10	41	4	estimation	estimation	NOUN
admet-10	41	5	is	be	AUX
admet-10	41	6	largely	largely	ADV
admet-10	41	7	based	base	VERB
admet-10	41	8	on	on	ADP
admet-10	41	9	the	the	DET
admet-10	41	10	pharmacology	pharmacology	NOUN
admet-10	41	11	and	and	CCONJ
admet-10	41	12	toxicity	toxicity	NOUN
admet-10	41	13	data	datum	NOUN
admet-10	41	14	,	,	PUNCT
admet-10	41	15	while	while	SCONJ
admet-10	41	16	pharmacokinetics	pharmacokinetic	NOUN
admet-10	41	17	is	be	AUX
admet-10	41	18	a	a	DET
admet-10	41	19	bridge	bridge	NOUN
admet-10	41	20	of	of	ADP
admet-10	41	21	pharmacology	pharmacology	NOUN
admet-10	41	22	and	and	CCONJ
admet-10	41	23	toxicity	toxicity	NOUN
admet-10	41	24	.	.	PUNCT
admet-10	42	1	however	however	ADV
admet-10	42	2	,	,	PUNCT
admet-10	42	3	the	the	DET
admet-10	42	4	design	design	NOUN
admet-10	42	5	of	of	ADP
admet-10	42	6	a	a	DET
admet-10	42	7	dose	dose	NOUN
admet-10	42	8	escalation	escalation	NOUN
admet-10	42	9	strategy	strategy	NOUN
admet-10	42	10	in	in	ADP
admet-10	42	11	clinical	clinical	ADJ
admet-10	42	12	studies	study	NOUN
admet-10	42	13	is	be	AUX
admet-10	42	14	beyond	beyond	ADP
admet-10	42	15	the	the	DET
admet-10	42	16	scope	scope	NOUN
admet-10	42	17	of	of	ADP
admet-10	42	18	this	this	DET
admet-10	42	19	article	article	NOUN
admet-10	42	20	.	.	PUNCT
admet-10	43	1	in	in	ADP
admet-10	43	2	the	the	DET
admet-10	43	3	next	next	ADJ
admet-10	43	4	section	section	NOUN
admet-10	43	5	(	(	PUNCT
admet-10	43	6	section	section	NOUN
admet-10	43	7	3	3	NUM
admet-10	43	8	)	)	PUNCT
admet-10	43	9	,	,	PUNCT
admet-10	43	10	we	we	PRON
admet-10	43	11	will	will	AUX
admet-10	43	12	discuss	discuss	VERB
admet-10	43	13	the	the	DET
admet-10	43	14	approach	approach	NOUN
admet-10	43	15	endorsed	endorse	VERB
admet-10	43	16	by	by	ADP
admet-10	43	17	fda	fda	PROPN
admet-10	43	18	for	for	ADP
admet-10	43	19	estimating	estimate	VERB
admet-10	43	20	the	the	DET
admet-10	43	21	maximum	maximum	ADJ
admet-10	43	22	safe	safe	ADJ
admet-10	43	23	starting	starting	NOUN
admet-10	43	24	dose	dose	VERB
admet-10	43	25	in	in	ADP
admet-10	43	26	initial	initial	ADJ
admet-10	43	27	clinical	clinical	ADJ
admet-10	43	28	trials	trial	NOUN
admet-10	43	29	.	.	PUNCT
admet-10	44	1	3	3	X
admet-10	44	2	.	.	X
admet-10	44	3	the	the	DET
admet-10	44	4	noael	noael	PROPN
admet-10	44	5	approach	approach	NOUN
admet-10	44	6	for	for	ADP
admet-10	44	7	dose	dose	NOUN
admet-10	44	8	selection	selection	NOUN
admet-10	44	9	there	there	PRON
admet-10	44	10	were	be	VERB
admet-10	44	11	different	different	ADJ
admet-10	44	12	approaches	approach	NOUN
admet-10	44	13	that	that	PRON
admet-10	44	14	could	could	AUX
admet-10	44	15	be	be	AUX
admet-10	44	16	used	use	VERB
admet-10	44	17	to	to	PART
admet-10	44	18	calculate	calculate	VERB
admet-10	44	19	the	the	DET
admet-10	44	20	starting	starting	NOUN
admet-10	44	21	dose	dose	VERB
admet-10	44	22	in	in	ADP
admet-10	44	23	fih	fih	NOUN
admet-10	44	24	studies	study	NOUN
admet-10	44	25	;	;	PUNCT
admet-10	44	26	to	to	PART
admet-10	44	27	name	name	VERB
admet-10	44	28	a	a	DET
admet-10	44	29	few	few	ADJ
admet-10	44	30	:	:	PUNCT
admet-10	44	31	noael	noael	ADJ
admet-10	44	32	from	from	ADP
admet-10	44	33	preclinical	preclinical	ADJ
admet-10	44	34	toxicology	toxicology	NOUN
admet-10	44	35	studies	study	NOUN
admet-10	44	36	multiplied	multiply	VERB
admet-10	44	37	by	by	ADP
admet-10	44	38	a	a	DET
admet-10	44	39	safety	safety	NOUN
admet-10	44	40	factor	factor	NOUN
admet-10	44	41	,	,	PUNCT
admet-10	44	42	the	the	DET
admet-10	44	43	similar	similar	ADJ
admet-10	44	44	drug	drug	NOUN
admet-10	44	45	approach	approach	NOUN
admet-10	44	46	and	and	CCONJ
admet-10	44	47	the	the	DET
admet-10	44	48	pharmacokinetically	pharmacokinetically	ADV
admet-10	44	49	guided	guide	VERB
admet-10	44	50	approach	approach	NOUN
admet-10	44	51	[	[	X
admet-10	44	52	11,12	11,12	NOUN
admet-10	44	53	]	]	PUNCT
admet-10	44	54	.	.	PUNCT
admet-10	45	1	estimating	estimate	VERB
admet-10	45	2	the	the	DET
admet-10	45	3	optimal	optimal	ADJ
admet-10	45	4	starting	starting	NOUN
admet-10	45	5	dose	dose	NOUN
admet-10	45	6	is	be	AUX
admet-10	45	7	complicated	complicated	ADJ
admet-10	45	8	,	,	PUNCT
admet-10	45	9	especially	especially	ADV
admet-10	45	10	when	when	SCONJ
admet-10	45	11	extrapolation	extrapolation	NOUN
admet-10	45	12	of	of	ADP
admet-10	45	13	doses	dose	NOUN
admet-10	45	14	from	from	ADP
admet-10	45	15	animals	animal	NOUN
admet-10	45	16	to	to	ADP
admet-10	45	17	humans	human	NOUN
admet-10	45	18	is	be	AUX
admet-10	45	19	based	base	VERB
admet-10	45	20	on	on	ADP
admet-10	45	21	multiple	multiple	ADJ
admet-10	45	22	assumptions	assumption	NOUN
admet-10	45	23	.	.	PUNCT
admet-10	46	1	indeed	indeed	ADV
admet-10	46	2	,	,	PUNCT
admet-10	46	3	different	different	ADJ
admet-10	46	4	methods	method	NOUN
admet-10	46	5	may	may	AUX
admet-10	46	6	yield	yield	VERB
admet-10	46	7	widely	widely	ADV
admet-10	46	8	varying	vary	VERB
admet-10	46	9	results	result	NOUN
admet-10	46	10	[	[	X
admet-10	46	11	11	11	NUM
admet-10	46	12	]	]	PUNCT
admet-10	46	13	.	.	PUNCT
admet-10	47	1	there	there	PRON
admet-10	47	2	was	be	VERB
admet-10	47	3	no	no	DET
admet-10	47	4	consensus	consensus	NOUN
admet-10	47	5	regarding	regard	VERB
admet-10	47	6	the	the	DET
admet-10	47	7	best	good	ADJ
admet-10	47	8	approach	approach	NOUN
admet-10	47	9	for	for	ADP
admet-10	47	10	estimating	estimate	VERB
admet-10	47	11	the	the	DET
admet-10	47	12	starting	starting	NOUN
admet-10	47	13	dose	dose	NOUN
admet-10	47	14	.	.	PUNCT
admet-10	48	1	it	it	PRON
admet-10	48	2	was	be	AUX
admet-10	48	3	not	not	PART
admet-10	48	4	until	until	ADP
admet-10	48	5	2005	2005	NUM
admet-10	48	6	,	,	PUNCT
admet-10	48	7	when	when	SCONJ
admet-10	48	8	the	the	DET
admet-10	48	9	fda	fda	PROPN
admet-10	48	10	issued	issue	VERB
admet-10	48	11	their	their	PRON
admet-10	48	12	guidance	guidance	NOUN
admet-10	48	13	[	[	X
admet-10	48	14	3	3	NUM
admet-10	48	15	]	]	PUNCT
admet-10	48	16	,	,	PUNCT
admet-10	48	17	that	that	SCONJ
admet-10	48	18	the	the	DET
admet-10	48	19	approach	approach	NOUN
admet-10	48	20	based	base	VERB
admet-10	48	21	on	on	ADP
admet-10	48	22	noael	noael	PROPN
admet-10	48	23	and	and	CCONJ
admet-10	48	24	safety	safety	NOUN
admet-10	48	25	factor	factor	NOUN
admet-10	48	26	became	become	VERB
admet-10	48	27	the	the	DET
admet-10	48	28	most	most	ADV
admet-10	48	29	common	common	ADJ
admet-10	48	30	method	method	NOUN
admet-10	48	31	for	for	ADP
admet-10	48	32	estimating	estimate	VERB
admet-10	48	33	the	the	DET
admet-10	48	34	starting	starting	NOUN
admet-10	48	35	dose	dose	NOUN
admet-10	48	36	.	.	PUNCT
admet-10	49	1	in	in	ADP
admet-10	49	2	the	the	DET
admet-10	49	3	following	follow	VERB
admet-10	49	4	discussion	discussion	NOUN
admet-10	49	5	,	,	PUNCT
admet-10	49	6	we	we	PRON
admet-10	49	7	will	will	AUX
admet-10	49	8	focus	focus	VERB
admet-10	49	9	on	on	ADP
admet-10	49	10	the	the	DET
admet-10	49	11	noael	noael	PROPN
admet-10	49	12	approach	approach	NOUN
admet-10	49	13	.	.	PUNCT
admet-10	50	1	readers	reader	NOUN
admet-10	50	2	who	who	PRON
admet-10	50	3	are	be	AUX
admet-10	50	4	interested	interested	ADJ
admet-10	50	5	in	in	ADP
admet-10	50	6	other	other	ADJ
admet-10	50	7	approaches	approach	NOUN
admet-10	50	8	are	be	AUX
admet-10	50	9	directed	direct	VERB
admet-10	50	10	to	to	ADP
admet-10	50	11	the	the	DET
admet-10	50	12	relevant	relevant	ADJ
admet-10	50	13	review	review	NOUN
admet-10	50	14	papers	paper	NOUN
admet-10	50	15	for	for	ADP
admet-10	50	16	methodological	methodological	ADJ
admet-10	50	17	details	detail	NOUN
admet-10	50	18	[	[	X
admet-10	50	19	11,12	11,12	NUM
admet-10	50	20	]	]	PUNCT
admet-10	50	21	.	.	PUNCT
admet-10	51	1	tam	tam	PROPN
admet-10	51	2	admet	admet	PROPN
admet-10	51	3	&	&	CCONJ
admet-10	51	4	dmpk	dmpk	PROPN
admet-10	51	5	1(4	1(4	NUM
admet-10	51	6	)	)	PUNCT
admet-10	51	7	(	(	PUNCT
admet-10	51	8	2013	2013	NUM
admet-10	51	9	)	)	PUNCT
admet-10	51	10	63	63	NUM
admet-10	51	11	-	-	SYM
admet-10	51	12	75	75	NUM
admet-10	51	13	66	66	NUM
admet-10	51	14	the	the	DET
admet-10	51	15	fda	fda	PROPN
admet-10	51	16	guidance	guidance	NOUN
admet-10	51	17	outlines	outline	VERB
admet-10	51	18	a	a	DET
admet-10	51	19	standardised	standardised	ADJ
admet-10	51	20	process	process	NOUN
admet-10	51	21	for	for	ADP
admet-10	51	22	deriving	derive	VERB
admet-10	51	23	the	the	DET
admet-10	51	24	maximum	maximum	ADJ
admet-10	51	25	recommended	recommend	VERB
admet-10	51	26	starting	starting	NOUN
admet-10	51	27	dose	dose	PROPN
admet-10	51	28	(	(	PUNCT
admet-10	51	29	mrsd	mrsd	ADJ
admet-10	51	30	)	)	PUNCT
admet-10	51	31	for	for	ADP
admet-10	51	32	adult	adult	NOUN
admet-10	51	33	healthy	healthy	ADJ
admet-10	51	34	volunteers	volunteer	NOUN
admet-10	51	35	in	in	ADP
admet-10	51	36	phase	phase	NOUN
admet-10	51	37	1	1	NUM
admet-10	51	38	studies	study	NOUN
admet-10	51	39	[	[	X
admet-10	51	40	3	3	NUM
admet-10	51	41	]	]	PUNCT
admet-10	51	42	.	.	PUNCT
admet-10	52	1	the	the	DET
admet-10	52	2	main	main	ADJ
admet-10	52	3	steps	step	NOUN
admet-10	52	4	of	of	ADP
admet-10	52	5	this	this	DET
admet-10	52	6	process	process	NOUN
admet-10	52	7	are	be	AUX
admet-10	52	8	:	:	PUNCT
admet-10	52	9	(	(	PUNCT
admet-10	52	10	1	1	X
admet-10	52	11	)	)	PUNCT
admet-10	52	12	the	the	DET
admet-10	52	13	determination	determination	NOUN
admet-10	52	14	of	of	ADP
admet-10	52	15	the	the	DET
admet-10	52	16	noaels	noael	NOUN
admet-10	52	17	in	in	ADP
admet-10	52	18	animal	animal	NOUN
admet-10	52	19	species	specie	NOUN
admet-10	52	20	,	,	PUNCT
admet-10	52	21	(	(	PUNCT
admet-10	52	22	2	2	X
admet-10	52	23	)	)	PUNCT
admet-10	52	24	the	the	DET
admet-10	52	25	conversion	conversion	NOUN
admet-10	52	26	of	of	ADP
admet-10	52	27	noaels	noael	NOUN
admet-10	52	28	to	to	ADP
admet-10	52	29	the	the	DET
admet-10	52	30	human	human	ADJ
admet-10	52	31	equivalent	equivalent	NOUN
admet-10	52	32	dose	dose	NOUN
admet-10	52	33	(	(	PUNCT
admet-10	52	34	he	he	PRON
admet-10	52	35	d	d	VERB
admet-10	52	36	)	)	PUNCT
admet-10	52	37	using	use	VERB
admet-10	52	38	the	the	DET
admet-10	52	39	allometric	allometric	ADJ
admet-10	52	40	scaling	scale	VERB
admet-10	52	41	factors	factor	NOUN
admet-10	52	42	listed	list	VERB
admet-10	52	43	in	in	ADP
admet-10	52	44	table	table	NOUN
admet-10	52	45	2	2	NUM
admet-10	52	46	,	,	PUNCT
admet-10	52	47	(	(	PUNCT
admet-10	52	48	3	3	X
admet-10	52	49	)	)	PUNCT
admet-10	52	50	selection	selection	NOUN
admet-10	52	51	of	of	ADP
admet-10	52	52	the	the	DET
admet-10	52	53	most	most	ADV
admet-10	52	54	appropriate	appropriate	ADJ
admet-10	52	55	animal	animal	NOUN
admet-10	52	56	species	specie	NOUN
admet-10	52	57	,	,	PUNCT
admet-10	52	58	and	and	CCONJ
admet-10	52	59	(	(	PUNCT
admet-10	52	60	4	4	X
admet-10	52	61	)	)	PUNCT
admet-10	52	62	the	the	DET
admet-10	52	63	application	application	NOUN
admet-10	52	64	of	of	ADP
admet-10	52	65	a	a	DET
admet-10	52	66	safety	safety	NOUN
admet-10	52	67	factor	factor	NOUN
admet-10	52	68	to	to	PART
admet-10	52	69	derive	derive	VERB
admet-10	52	70	the	the	DET
admet-10	52	71	mrsd	mrsd	ADJ
admet-10	52	72	.	.	PUNCT
admet-10	52	73	table	table	NOUN
admet-10	52	74	2	2	NUM
admet-10	52	75	.	.	PUNCT
admet-10	52	76	conversion	conversion	NOUN
admet-10	52	77	factors	factor	NOUN
admet-10	52	78	of	of	ADP
admet-10	52	79	animal	animal	NOUN
admet-10	52	80	doses	dose	NOUN
admet-10	52	81	to	to	ADP
admet-10	52	82	human	human	ADJ
admet-10	52	83	equivalent	equivalent	ADJ
admet-10	52	84	doses	dose	NOUN
admet-10	52	85	[	[	X
admet-10	52	86	3	3	NUM
admet-10	52	87	]	]	X
admet-10	52	88	species	specie	NOUN
admet-10	52	89	to	to	PART
admet-10	52	90	convert	convert	VERB
admet-10	52	91	animal	animal	NOUN
admet-10	52	92	dose	dose	NOUN
admet-10	52	93	in	in	ADP
admet-10	52	94	mg	mg	PROPN
admet-10	52	95	/	/	SYM
admet-10	52	96	kg	kg	PROPN
admet-10	52	97	to	to	ADP
admet-10	52	98	he	he	PRON
admet-10	52	99	d	d	PROPN
admet-10	52	100	mg	mg	PROPN
admet-10	52	101	/	/	SYM
admet-10	52	102	m	m	PROPN
admet-10	52	103	2	2	NUM
admet-10	52	104	,	,	PUNCT
admet-10	52	105	multiply	multiply	ADV
admet-10	52	106	by	by	ADP
admet-10	52	107	km	km	NOUN
admet-10	52	108	+	+	CCONJ
admet-10	52	109	to	to	PART
admet-10	52	110	convert	convert	VERB
admet-10	52	111	animal	animal	NOUN
admet-10	52	112	dose	dose	NOUN
admet-10	52	113	in	in	ADP
admet-10	52	114	mg	mg	PROPN
admet-10	52	115	/	/	SYM
admet-10	52	116	kg	kg	PROPN
admet-10	52	117	to	to	ADP
admet-10	52	118	he	he	PRON
admet-10	52	119	d	d	PROPN
admet-10	52	120	*	*	PUNCT
admet-10	52	121	in	in	ADP
admet-10	52	122	mg	mg	PROPN
admet-10	52	123	/	/	SYM
admet-10	52	124	kg	kg	PROPN
admet-10	52	125	,	,	PUNCT
admet-10	52	126	either	either	ADV
admet-10	52	127	:	:	PUNCT
admet-10	52	128	divide	divide	NOUN
admet-10	52	129	animal	animal	NOUN
admet-10	52	130	dose	dose	VERB
admet-10	52	131	by	by	ADP
admet-10	52	132	multiply	multiply	NOUN
admet-10	52	133	animal	animal	NOUN
admet-10	52	134	dose	dose	VERB
admet-10	52	135	by	by	ADP
admet-10	52	136	human	human	PROPN
admet-10	52	137	37	37	NUM
admet-10	52	138	mouse	mouse	NOUN
admet-10	52	139	3	3	NUM
admet-10	52	140	12.3	12.3	NUM
admet-10	52	141	0.08	0.08	NUM
admet-10	52	142	hamster	hamster	NOUN
admet-10	52	143	5	5	NUM
admet-10	52	144	7.4	7.4	NUM
admet-10	52	145	0.13	0.13	NUM
admet-10	52	146	rat	rat	NOUN
admet-10	52	147	6	6	NUM
admet-10	52	148	6.2	6.2	NUM
admet-10	52	149	0.16	0.16	NUM
admet-10	52	150	ferret	ferret	NOUN
admet-10	52	151	7	7	NUM
admet-10	52	152	5.3	5.3	NUM
admet-10	52	153	0.19	0.19	NUM
admet-10	52	154	guinea	guinea	NOUN
admet-10	52	155	pig	pig	NOUN
admet-10	52	156	8	8	NUM
admet-10	52	157	4.6	4.6	NUM
admet-10	52	158	0.22	0.22	NUM
admet-10	52	159	rabbit	rabbit	NOUN
admet-10	52	160	12	12	NUM
admet-10	52	161	3.1	3.1	NUM
admet-10	52	162	0.32	0.32	NUM
admet-10	52	163	dog	dog	NOUN
admet-10	52	164	20	20	NUM
admet-10	52	165	1.8	1.8	NUM
admet-10	52	166	0.54	0.54	NUM
admet-10	52	167	monkeys	monkey	NOUN
admet-10	52	168	12	12	NUM
admet-10	52	169	3.1	3.1	NUM
admet-10	52	170	0.32	0.32	NUM
admet-10	52	171	marmoset	marmoset	NOUN
admet-10	52	172	6	6	NUM
admet-10	52	173	6.2	6.2	NUM
admet-10	52	174	0.16	0.16	NUM
admet-10	52	175	squirrel	squirrel	NOUN
admet-10	52	176	monkey	monkey	NOUN
admet-10	52	177	7	7	NUM
admet-10	52	178	5.3	5.3	NUM
admet-10	52	179	0.19	0.19	NUM
admet-10	52	180	baboon	baboon	NOUN
admet-10	52	181	20	20	NUM
admet-10	52	182	1.8	1.8	NUM
admet-10	52	183	0.54	0.54	NUM
admet-10	52	184	*	*	PUNCT
admet-10	52	185	assumes	assume	VERB
admet-10	52	186	60	60	NUM
admet-10	52	187	kg	kg	NOUN
admet-10	52	188	human	human	NOUN
admet-10	52	189	.	.	PUNCT
admet-10	53	1	for	for	ADP
admet-10	53	2	species	specie	NOUN
admet-10	53	3	not	not	PART
admet-10	53	4	listed	list	VERB
admet-10	53	5	or	or	CCONJ
admet-10	53	6	for	for	ADP
admet-10	53	7	weights	weight	NOUN
admet-10	53	8	outside	outside	ADP
admet-10	53	9	the	the	DET
admet-10	53	10	standard	standard	ADJ
admet-10	53	11	ranges	range	NOUN
admet-10	53	12	,	,	PUNCT
admet-10	53	13	he	he	PRON
admet-10	53	14	d	d	NOUN
admet-10	53	15	can	can	AUX
admet-10	53	16	be	be	AUX
admet-10	53	17	calculated	calculate	VERB
admet-10	53	18	from	from	ADP
admet-10	53	19	the	the	DET
admet-10	53	20	following	follow	VERB
admet-10	53	21	formula	formula	NOUN
admet-10	53	22	:	:	PUNCT
admet-10	53	23	he	he	PRON
admet-10	53	24	d	d	NOUN
admet-10	53	25	=	=	PUNCT
admet-10	53	26	animal	animal	NOUN
admet-10	53	27	dose	dose	NOUN
admet-10	53	28	(	(	PUNCT
admet-10	53	29	mg	mg	PROPN
admet-10	53	30	/	/	SYM
admet-10	53	31	kg	kg	NOUN
admet-10	53	32	)	)	PUNCT
admet-10	53	33	×	×	NOUN
admet-10	53	34	(	(	PUNCT
admet-10	53	35	animal	animal	NOUN
admet-10	53	36	wt	wt	NOUN
admet-10	53	37	.	.	PUNCT
admet-10	54	1	(	(	PUNCT
admet-10	54	2	kg)/human	kg)/human	PROPN
admet-10	54	3	wt	wt	PROPN
admet-10	54	4	.	.	PUNCT
admet-10	54	5	(	(	PUNCT
admet-10	54	6	kg	kg	NOUN
admet-10	54	7	)	)	PUNCT
admet-10	54	8	)	)	PUNCT
admet-10	55	1	0.33	0.33	NUM
admet-10	56	1	+	+	NUM
admet-10	56	2	factor	factor	NOUN
admet-10	56	3	for	for	ADP
admet-10	56	4	converting	convert	VERB
admet-10	56	5	mg	mg	PROPN
admet-10	56	6	/	/	SYM
admet-10	56	7	kg	kg	PROPN
admet-10	56	8	dose	dose	VERB
admet-10	56	9	to	to	ADP
admet-10	56	10	mg	mg	PROPN
admet-10	56	11	/	/	SYM
admet-10	56	12	m	m	PROPN
admet-10	56	13	2	2	NUM
admet-10	56	14	dose	dose	NOUN
admet-10	56	15	step	step	NOUN
admet-10	56	16	1	1	NUM
admet-10	56	17	:	:	PUNCT
admet-10	56	18	noael	noael	ADJ
admet-10	56	19	determination	determination	NOUN
admet-10	56	20	this	this	PRON
admet-10	56	21	is	be	AUX
admet-10	56	22	the	the	DET
admet-10	56	23	first	first	ADJ
admet-10	56	24	step	step	NOUN
admet-10	56	25	in	in	ADP
admet-10	56	26	the	the	DET
admet-10	56	27	process	process	NOUN
admet-10	56	28	,	,	PUNCT
admet-10	56	29	which	which	PRON
admet-10	56	30	involves	involve	VERB
admet-10	56	31	the	the	DET
admet-10	56	32	evaluation	evaluation	NOUN
admet-10	56	33	of	of	ADP
admet-10	56	34	the	the	DET
admet-10	56	35	available	available	ADJ
admet-10	56	36	animal	animal	NOUN
admet-10	56	37	data	datum	NOUN
admet-10	56	38	to	to	PART
admet-10	56	39	determine	determine	VERB
admet-10	56	40	the	the	DET
admet-10	56	41	noaels	noael	NOUN
admet-10	56	42	from	from	ADP
admet-10	56	43	toxicology	toxicology	NOUN
admet-10	56	44	studies	study	NOUN
admet-10	56	45	.	.	PUNCT
admet-10	57	1	here	here	ADV
admet-10	57	2	,	,	PUNCT
admet-10	57	3	the	the	DET
admet-10	57	4	noael	noael	PROPN
admet-10	57	5	refers	refer	VERB
admet-10	57	6	to	to	ADP
admet-10	57	7	the	the	DET
admet-10	57	8	highest	high	ADJ
admet-10	57	9	dose	dose	NOUN
admet-10	57	10	level	level	NOUN
admet-10	57	11	that	that	PRON
admet-10	57	12	does	do	AUX
admet-10	57	13	not	not	PART
admet-10	57	14	produce	produce	VERB
admet-10	57	15	significant	significant	ADJ
admet-10	57	16	adverse	adverse	ADJ
admet-10	57	17	effects	effect	NOUN
admet-10	57	18	compared	compare	VERB
admet-10	57	19	with	with	ADP
admet-10	57	20	the	the	DET
admet-10	57	21	control	control	NOUN
admet-10	57	22	group	group	NOUN
admet-10	57	23	.	.	PUNCT
admet-10	58	1	biologically	biologically	ADV
admet-10	58	2	significant	significant	ADJ
admet-10	58	3	or	or	CCONJ
admet-10	58	4	pd	pd	NOUN
admet-10	58	5	effects	effect	NOUN
admet-10	58	6	are	be	AUX
admet-10	58	7	acceptable	acceptable	ADJ
admet-10	58	8	provided	provide	VERB
admet-10	58	9	that	that	SCONJ
admet-10	58	10	they	they	PRON
admet-10	58	11	do	do	AUX
admet-10	58	12	not	not	PART
admet-10	58	13	raise	raise	VERB
admet-10	58	14	a	a	DET
admet-10	58	15	safety	safety	NOUN
admet-10	58	16	concern	concern	NOUN
admet-10	58	17	.	.	PUNCT
admet-10	59	1	the	the	DET
admet-10	59	2	adverse	adverse	ADJ
admet-10	59	3	effects	effect	NOUN
admet-10	59	4	used	use	VERB
admet-10	59	5	to	to	PART
admet-10	59	6	define	define	VERB
admet-10	59	7	the	the	DET
admet-10	59	8	noael	noael	PROPN
admet-10	59	9	should	should	AUX
admet-10	59	10	be	be	AUX
admet-10	59	11	based	base	VERB
admet-10	59	12	on	on	ADP
admet-10	59	13	an	an	DET
admet-10	59	14	effect	effect	NOUN
admet-10	59	15	that	that	PRON
admet-10	59	16	would	would	AUX
admet-10	59	17	be	be	AUX
admet-10	59	18	unacceptable	unacceptable	ADJ
admet-10	59	19	if	if	SCONJ
admet-10	59	20	produced	produce	VERB
admet-10	59	21	by	by	ADP
admet-10	59	22	the	the	DET
admet-10	59	23	initial	initial	ADJ
admet-10	59	24	dose	dose	NOUN
admet-10	59	25	in	in	ADP
admet-10	59	26	a	a	DET
admet-10	59	27	phase	phase	NOUN
admet-10	59	28	i	i	PRON
admet-10	59	29	clinical	clinical	ADJ
admet-10	59	30	trial	trial	NOUN
admet-10	59	31	.	.	PUNCT
admet-10	60	1	the	the	DET
admet-10	60	2	noael	noael	PROPN
admet-10	60	3	for	for	ADP
admet-10	60	4	each	each	DET
admet-10	60	5	toxicology	toxicology	NOUN
admet-10	60	6	study	study	NOUN
admet-10	60	7	is	be	AUX
admet-10	60	8	usually	usually	ADV
admet-10	60	9	reported	report	VERB
admet-10	60	10	in	in	ADP
admet-10	60	11	mg	mg	PROPN
admet-10	60	12	/	/	SYM
admet-10	60	13	kg	kg	PROPN
admet-10	60	14	.	.	PUNCT
admet-10	60	15	step	step	NOUN
admet-10	60	16	2	2	NUM
admet-10	60	17	:	:	PUNCT
admet-10	60	18	he	he	PRON
admet-10	60	19	d	d	PROPN
admet-10	60	20	calculation	calculation	VERB
admet-10	60	21	the	the	DET
admet-10	60	22	noael	noael	PROPN
admet-10	60	23	for	for	ADP
admet-10	60	24	each	each	DET
admet-10	60	25	tested	test	VERB
admet-10	60	26	species	specie	NOUN
admet-10	60	27	should	should	AUX
admet-10	60	28	be	be	AUX
admet-10	60	29	determined	determine	VERB
admet-10	60	30	,	,	PUNCT
admet-10	60	31	and	and	CCONJ
admet-10	60	32	then	then	ADV
admet-10	60	33	converted	convert	VERB
admet-10	60	34	to	to	ADP
admet-10	60	35	the	the	DET
admet-10	60	36	he	he	PRON
admet-10	60	37	d	d	PROPN
admet-10	60	38	using	use	VERB
admet-10	60	39	appropriate	appropriate	ADJ
admet-10	60	40	scaling	scaling	NOUN
admet-10	60	41	factors	factor	NOUN
admet-10	60	42	,	,	PUNCT
admet-10	60	43	as	as	SCONJ
admet-10	60	44	shown	show	VERB
admet-10	60	45	in	in	ADP
admet-10	60	46	table	table	NOUN
admet-10	60	47	2	2	NUM
admet-10	60	48	.	.	PUNCT
admet-10	61	1	for	for	ADP
admet-10	61	2	systemically	systemically	ADV
admet-10	61	3	administered	administer	VERB
admet-10	61	4	agents	agent	NOUN
admet-10	61	5	,	,	PUNCT
admet-10	61	6	the	the	DET
admet-10	61	7	conversion	conversion	NOUN
admet-10	61	8	should	should	AUX
admet-10	61	9	be	be	AUX
admet-10	61	10	based	base	VERB
admet-10	61	11	on	on	ADP
admet-10	61	12	the	the	DET
admet-10	61	13	normalisation	normalisation	NOUN
admet-10	61	14	of	of	ADP
admet-10	61	15	doses	dose	NOUN
admet-10	61	16	to	to	ADP
admet-10	61	17	body	body	NOUN
admet-10	61	18	surface	surface	NOUN
admet-10	61	19	area	area	NOUN
admet-10	61	20	(	(	PUNCT
admet-10	61	21	assumed	assume	VERB
admet-10	61	22	doses	dose	NOUN
admet-10	61	23	scaled	scale	VERB
admet-10	61	24	1:1	1:1	NUM
admet-10	61	25	when	when	SCONJ
admet-10	61	26	admet	admet	PROPN
admet-10	61	27	&	&	CCONJ
admet-10	61	28	dmpk	dmpk	PROPN
admet-10	61	29	1(4	1(4	NUM
admet-10	61	30	)	)	PUNCT
admet-10	61	31	(	(	PUNCT
admet-10	61	32	2013	2013	NUM
admet-10	61	33	)	)	PUNCT
admet-10	61	34	63	63	NUM
admet-10	61	35	-	-	SYM
admet-10	61	36	75	75	NUM
admet-10	61	37	estimating	estimate	VERB
admet-10	61	38	first	first	ADV
admet-10	61	39	in	in	ADP
admet-10	61	40	human	human	PROPN
admet-10	61	41	dose	dose	NOUN
admet-10	61	42	doi	doi	PROPN
admet-10	61	43	:	:	PUNCT
admet-10	61	44	10.5599	10.5599	NUM
admet-10	61	45	/	/	SYM
admet-10	61	46	admet.1.4.10	admet.1.4.10	ADJ
admet-10	61	47	67	67	NUM
admet-10	61	48	normalized	normalize	VERB
admet-10	61	49	to	to	ADP
admet-10	61	50	body	body	NOUN
admet-10	61	51	surface	surface	NOUN
admet-10	61	52	area	area	NOUN
admet-10	61	53	)	)	PUNCT
admet-10	61	54	.	.	PUNCT
admet-10	62	1	there	there	PRON
admet-10	62	2	are	be	VERB
admet-10	62	3	exceptions	exception	NOUN
admet-10	62	4	where	where	SCONJ
admet-10	62	5	the	the	DET
admet-10	62	6	mg	mg	PROPN
admet-10	62	7	/	/	SYM
admet-10	62	8	m	m	NOUN
admet-10	62	9	2	2	NUM
admet-10	62	10	scaling	scaling	NOUN
admet-10	62	11	between	between	ADP
admet-10	62	12	species	specie	NOUN
admet-10	62	13	is	be	AUX
admet-10	62	14	not	not	PART
admet-10	62	15	expected	expect	VERB
admet-10	62	16	to	to	PART
admet-10	62	17	work	work	VERB
admet-10	62	18	well	well	ADV
admet-10	62	19	.	.	PUNCT
admet-10	63	1	these	these	PRON
admet-10	63	2	include	include	VERB
admet-10	63	3	:	:	PUNCT
admet-10	63	4	therapeutics	therapeutic	NOUN
admet-10	63	5	administered	administer	VERB
admet-10	63	6	by	by	ADP
admet-10	63	7	alternative	alternative	ADJ
admet-10	63	8	routes	route	NOUN
admet-10	63	9	(	(	PUNCT
admet-10	63	10	e.g.	e.g.	ADV
admet-10	63	11	,	,	PUNCT
admet-10	63	12	topical	topical	ADJ
admet-10	63	13	,	,	PUNCT
admet-10	63	14	intranasal	intranasal	NOUN
admet-10	63	15	,	,	PUNCT
admet-10	63	16	subcutaneous	subcutaneous	ADJ
admet-10	63	17	,	,	PUNCT
admet-10	63	18	intramuscular	intramuscular	ADJ
admet-10	63	19	,	,	PUNCT
admet-10	63	20	intrathecal	intrathecal	ADJ
admet-10	63	21	,	,	PUNCT
admet-10	63	22	intravesical	intravesical	ADJ
admet-10	63	23	,	,	PUNCT
admet-10	63	24	intraocular	intraocular	ADJ
admet-10	63	25	,	,	PUNCT
admet-10	63	26	or	or	CCONJ
admet-10	63	27	intrapleural	intrapleural	ADJ
admet-10	63	28	)	)	PUNCT
admet-10	63	29	and	and	CCONJ
admet-10	63	30	proteins	protein	NOUN
admet-10	63	31	administered	administer	VERB
admet-10	63	32	intravascularly	intravascularly	ADV
admet-10	63	33	.	.	PUNCT
admet-10	64	1	in	in	ADP
admet-10	64	2	such	such	ADJ
admet-10	64	3	cases	case	NOUN
admet-10	64	4	,	,	PUNCT
admet-10	64	5	alternative	alternative	ADJ
admet-10	64	6	means	mean	NOUN
admet-10	64	7	of	of	ADP
admet-10	64	8	normalisation	normalisation	NOUN
admet-10	64	9	should	should	AUX
admet-10	64	10	be	be	AUX
admet-10	64	11	utilised	utilise	VERB
admet-10	64	12	[	[	PUNCT
admet-10	64	13	3	3	NUM
admet-10	64	14	]	]	PUNCT
admet-10	64	15	.	.	PUNCT
admet-10	65	1	conversion	conversion	NOUN
admet-10	65	2	of	of	ADP
admet-10	65	3	the	the	DET
admet-10	65	4	animal	animal	NOUN
admet-10	65	5	noael	noael	NOUN
admet-10	65	6	to	to	ADP
admet-10	65	7	the	the	DET
admet-10	65	8	he	he	PRON
admet-10	65	9	d	d	PROPN
admet-10	65	10	should	should	AUX
admet-10	65	11	be	be	AUX
admet-10	65	12	normalised	normalise	VERB
admet-10	65	13	to	to	ADP
admet-10	65	14	mg	mg	PROPN
admet-10	65	15	/	/	SYM
admet-10	65	16	kg	kg	PROPN
admet-10	65	17	.	.	PUNCT
admet-10	66	1	the	the	DET
admet-10	66	2	species	specie	NOUN
admet-10	66	3	that	that	PRON
admet-10	66	4	generates	generate	VERB
admet-10	66	5	the	the	DET
admet-10	66	6	lowest	low	ADJ
admet-10	66	7	he	he	PRON
admet-10	66	8	d	d	PROPN
admet-10	66	9	is	be	AUX
admet-10	66	10	referred	refer	VERB
admet-10	66	11	to	to	ADP
admet-10	66	12	as	as	ADP
admet-10	66	13	the	the	DET
admet-10	66	14	most	most	ADV
admet-10	66	15	sensitive	sensitive	ADJ
admet-10	66	16	species	specie	NOUN
admet-10	66	17	.	.	PUNCT
admet-10	67	1	step	step	NOUN
admet-10	67	2	3	3	NUM
admet-10	67	3	:	:	PUNCT
admet-10	67	4	selection	selection	NOUN
admet-10	67	5	of	of	ADP
admet-10	67	6	the	the	DET
admet-10	67	7	most	most	ADV
admet-10	67	8	appropriate	appropriate	ADJ
admet-10	67	9	species	specie	NOUN
admet-10	67	10	in	in	ADP
admet-10	67	11	the	the	DET
admet-10	67	12	absence	absence	NOUN
admet-10	67	13	of	of	ADP
admet-10	67	14	any	any	DET
admet-10	67	15	information	information	NOUN
admet-10	67	16	to	to	PART
admet-10	67	17	aid	aid	VERB
admet-10	67	18	the	the	DET
admet-10	67	19	selection	selection	NOUN
admet-10	67	20	of	of	ADP
admet-10	67	21	species	specie	NOUN
admet-10	67	22	to	to	PART
admet-10	67	23	assess	assess	VERB
admet-10	67	24	the	the	DET
admet-10	67	25	risk	risk	NOUN
admet-10	67	26	in	in	ADP
admet-10	67	27	humans	human	NOUN
admet-10	67	28	,	,	PUNCT
admet-10	67	29	the	the	DET
admet-10	67	30	most	most	ADV
admet-10	67	31	sensitive	sensitive	ADJ
admet-10	67	32	species	specie	NOUN
admet-10	67	33	is	be	AUX
admet-10	67	34	then	then	ADV
admet-10	67	35	regarded	regard	VERB
admet-10	67	36	as	as	ADP
admet-10	67	37	the	the	DET
admet-10	67	38	most	most	ADV
admet-10	67	39	appropriate	appropriate	ADJ
admet-10	67	40	,	,	PUNCT
admet-10	67	41	since	since	SCONJ
admet-10	67	42	the	the	DET
admet-10	67	43	use	use	NOUN
admet-10	67	44	of	of	ADP
admet-10	67	45	the	the	DET
admet-10	67	46	lowest	low	ADJ
admet-10	67	47	he	he	PRON
admet-10	67	48	d	d	PROPN
admet-10	67	49	would	would	AUX
admet-10	67	50	generate	generate	VERB
admet-10	67	51	the	the	DET
admet-10	67	52	most	most	ADV
admet-10	67	53	conservative	conservative	ADJ
admet-10	67	54	starting	starting	NOUN
admet-10	67	55	dose	dose	PROPN
admet-10	67	56	.	.	PUNCT
admet-10	68	1	however	however	ADV
admet-10	68	2	,	,	PUNCT
admet-10	68	3	if	if	SCONJ
admet-10	68	4	there	there	PRON
admet-10	68	5	is	be	VERB
admet-10	68	6	information	information	NOUN
admet-10	68	7	suggesting	suggest	VERB
admet-10	68	8	a	a	DET
admet-10	68	9	particular	particular	ADJ
admet-10	68	10	species	specie	NOUN
admet-10	68	11	is	be	AUX
admet-10	68	12	more	more	ADV
admet-10	68	13	relevant	relevant	ADJ
admet-10	68	14	for	for	ADP
admet-10	68	15	assessing	assess	VERB
admet-10	68	16	the	the	DET
admet-10	68	17	risk	risk	NOUN
admet-10	68	18	in	in	ADP
admet-10	68	19	humans	human	NOUN
admet-10	68	20	,	,	PUNCT
admet-10	68	21	the	the	DET
admet-10	68	22	he	he	PRON
admet-10	68	23	d	d	PROPN
admet-10	68	24	of	of	ADP
admet-10	68	25	that	that	DET
admet-10	68	26	species	specie	NOUN
admet-10	68	27	could	could	AUX
admet-10	68	28	be	be	AUX
admet-10	68	29	used	use	VERB
admet-10	68	30	.	.	PUNCT
admet-10	69	1	step	step	NOUN
admet-10	69	2	4	4	NUM
admet-10	69	3	:	:	PUNCT
admet-10	69	4	application	application	NOUN
admet-10	69	5	of	of	ADP
admet-10	69	6	safety	safety	NOUN
admet-10	69	7	factor	factor	NOUN
admet-10	69	8	a	a	DET
admet-10	69	9	safety	safety	NOUN
admet-10	69	10	factor	factor	NOUN
admet-10	69	11	should	should	AUX
admet-10	69	12	then	then	ADV
admet-10	69	13	be	be	AUX
admet-10	69	14	applied	apply	VERB
admet-10	69	15	to	to	ADP
admet-10	69	16	the	the	DET
admet-10	69	17	he	he	PRON
admet-10	69	18	d	d	NOUN
admet-10	69	19	to	to	PART
admet-10	69	20	provide	provide	VERB
admet-10	69	21	a	a	DET
admet-10	69	22	margin	margin	NOUN
admet-10	69	23	of	of	ADP
admet-10	69	24	safety	safety	NOUN
admet-10	69	25	for	for	ADP
admet-10	69	26	protection	protection	NOUN
admet-10	69	27	of	of	ADP
admet-10	69	28	human	human	ADJ
admet-10	69	29	subjects	subject	NOUN
admet-10	69	30	receiving	receive	VERB
admet-10	69	31	the	the	DET
admet-10	69	32	initial	initial	ADJ
admet-10	69	33	clinical	clinical	ADJ
admet-10	69	34	dose	dose	NOUN
admet-10	69	35	.	.	PUNCT
admet-10	70	1	the	the	DET
admet-10	70	2	mrsd	mrsd	NOUN
admet-10	70	3	is	be	AUX
admet-10	70	4	obtained	obtain	VERB
admet-10	70	5	by	by	ADP
admet-10	70	6	dividing	divide	VERB
admet-10	70	7	the	the	DET
admet-10	70	8	he	he	PRON
admet-10	70	9	d	d	PROPN
admet-10	70	10	by	by	ADP
admet-10	70	11	the	the	DET
admet-10	70	12	safety	safety	NOUN
admet-10	70	13	factor	factor	NOUN
admet-10	70	14	;	;	PUNCT
admet-10	70	15	the	the	DET
admet-10	70	16	default	default	NOUN
admet-10	70	17	safety	safety	NOUN
admet-10	70	18	factor	factor	NOUN
admet-10	70	19	is	be	AUX
admet-10	70	20	10	10	NUM
admet-10	70	21	.	.	PUNCT
admet-10	71	1	this	this	PRON
admet-10	71	2	is	be	AUX
admet-10	71	3	a	a	DET
admet-10	71	4	historically	historically	ADV
admet-10	71	5	accepted	accept	VERB
admet-10	71	6	value	value	NOUN
admet-10	71	7	,	,	PUNCT
admet-10	71	8	but	but	CCONJ
admet-10	71	9	should	should	AUX
admet-10	71	10	be	be	AUX
admet-10	71	11	evaluated	evaluate	VERB
admet-10	71	12	based	base	VERB
admet-10	71	13	on	on	ADP
admet-10	71	14	available	available	ADJ
admet-10	71	15	information	information	NOUN
admet-10	71	16	.	.	PUNCT
admet-10	72	1	for	for	ADP
admet-10	72	2	instance	instance	NOUN
admet-10	72	3	,	,	PUNCT
admet-10	72	4	the	the	DET
admet-10	72	5	safety	safety	NOUN
admet-10	72	6	factor	factor	NOUN
admet-10	72	7	should	should	AUX
admet-10	72	8	be	be	AUX
admet-10	72	9	increased	increase	VERB
admet-10	72	10	in	in	ADP
admet-10	72	11	situations	situation	NOUN
admet-10	72	12	in	in	ADP
admet-10	72	13	which	which	PRON
admet-10	72	14	steep	steep	ADJ
admet-10	72	15	dose	dose	NOUN
admet-10	72	16	–	–	PUNCT
admet-10	72	17	response	response	NOUN
admet-10	72	18	curve	curve	NOUN
admet-10	72	19	,	,	PUNCT
admet-10	72	20	severe	severe	ADJ
admet-10	72	21	/	/	SYM
admet-10	72	22	irreversible	irreversible	ADJ
admet-10	72	23	toxicities	toxicity	NOUN
admet-10	72	24	,	,	PUNCT
admet-10	72	25	unexplained	unexplained	ADJ
admet-10	72	26	mortality	mortality	NOUN
admet-10	72	27	,	,	PUNCT
admet-10	72	28	variability	variability	NOUN
admet-10	72	29	in	in	ADP
admet-10	72	30	doses	dose	NOUN
admet-10	72	31	or	or	CCONJ
admet-10	72	32	drug	drug	NOUN
admet-10	72	33	levels	level	NOUN
admet-10	72	34	eliciting	elicit	VERB
admet-10	72	35	effects	effect	NOUN
admet-10	72	36	,	,	PUNCT
admet-10	72	37	variable	variable	ADJ
admet-10	72	38	bioavailability	bioavailability	NOUN
admet-10	72	39	,	,	PUNCT
admet-10	72	40	or	or	CCONJ
admet-10	72	41	nonlinear	nonlinear	ADJ
admet-10	72	42	pharmacokinetics	pharmacokinetic	NOUN
admet-10	72	43	were	be	AUX
admet-10	72	44	seen	see	VERB
admet-10	72	45	in	in	ADP
admet-10	72	46	preclinical	preclinical	ADJ
admet-10	72	47	studies	study	NOUN
admet-10	72	48	.	.	PUNCT
admet-10	73	1	it	it	PRON
admet-10	73	2	can	can	AUX
admet-10	73	3	be	be	AUX
admet-10	73	4	seen	see	VERB
admet-10	73	5	that	that	SCONJ
admet-10	73	6	the	the	DET
admet-10	73	7	mrsd	mrsd	NOUN
admet-10	73	8	was	be	AUX
admet-10	73	9	derived	derive	VERB
admet-10	73	10	based	base	VERB
admet-10	73	11	on	on	ADP
admet-10	73	12	the	the	DET
admet-10	73	13	adverse	adverse	ADJ
admet-10	73	14	effects	effect	NOUN
admet-10	73	15	seen	see	VERB
admet-10	73	16	in	in	ADP
admet-10	73	17	preclinical	preclinical	ADJ
admet-10	73	18	toxicology	toxicology	NOUN
admet-10	73	19	studies	study	NOUN
admet-10	73	20	.	.	PUNCT
admet-10	74	1	near	near	ADP
admet-10	74	2	the	the	DET
admet-10	74	3	end	end	NOUN
admet-10	74	4	of	of	ADP
admet-10	74	5	the	the	DET
admet-10	74	6	fda	fda	PROPN
admet-10	74	7	guidance	guidance	NOUN
admet-10	74	8	document	document	NOUN
admet-10	74	9	[	[	X
admet-10	74	10	3	3	NUM
admet-10	74	11	]	]	PUNCT
admet-10	74	12	,	,	PUNCT
admet-10	74	13	there	there	PRON
admet-10	74	14	is	be	VERB
admet-10	74	15	brief	brief	ADJ
admet-10	74	16	mention	mention	NOUN
admet-10	74	17	of	of	ADP
admet-10	74	18	the	the	DET
admet-10	74	19	merits	merit	NOUN
admet-10	74	20	of	of	ADP
admet-10	74	21	comparing	compare	VERB
admet-10	74	22	the	the	DET
admet-10	74	23	mrsd	mrsd	NOUN
admet-10	74	24	with	with	ADP
admet-10	74	25	pharmacological	pharmacological	ADJ
admet-10	74	26	active	active	ADJ
admet-10	74	27	dose	dose	NOUN
admet-10	74	28	(	(	PUNCT
admet-10	74	29	pad	pad	NOUN
admet-10	74	30	)	)	PUNCT
admet-10	74	31	derived	derive	VERB
admet-10	74	32	from	from	ADP
admet-10	74	33	appropriate	appropriate	ADJ
admet-10	74	34	pd	pd	NOUN
admet-10	74	35	models	model	NOUN
admet-10	74	36	,	,	PUNCT
admet-10	74	37	and	and	CCONJ
admet-10	74	38	adjusting	adjust	VERB
admet-10	74	39	/	/	SYM
admet-10	74	40	reducing	reduce	VERB
admet-10	74	41	the	the	DET
admet-10	74	42	fih	fih	NOUN
admet-10	74	43	dose	dose	NOUN
admet-10	74	44	accordingly	accordingly	ADV
admet-10	74	45	.	.	PUNCT
admet-10	75	1	for	for	ADP
admet-10	75	2	certain	certain	ADJ
admet-10	75	3	classes	class	NOUN
admet-10	75	4	of	of	ADP
admet-10	75	5	drug	drug	NOUN
admet-10	75	6	or	or	CCONJ
admet-10	75	7	biologics	biologic	NOUN
admet-10	75	8	,	,	PUNCT
admet-10	75	9	the	the	DET
admet-10	75	10	toxicity	toxicity	NOUN
admet-10	75	11	may	may	AUX
admet-10	75	12	arise	arise	VERB
admet-10	75	13	from	from	ADP
admet-10	75	14	exaggerated	exaggerated	ADJ
admet-10	75	15	pharmacologic	pharmacologic	ADJ
admet-10	75	16	effects	effect	NOUN
admet-10	75	17	,	,	PUNCT
admet-10	75	18	so	so	SCONJ
admet-10	75	19	the	the	DET
admet-10	75	20	pad	pad	NOUN
admet-10	75	21	could	could	AUX
admet-10	75	22	be	be	AUX
admet-10	75	23	a	a	DET
admet-10	75	24	more	more	ADV
admet-10	75	25	sensitive	sensitive	ADJ
admet-10	75	26	indicator	indicator	NOUN
admet-10	75	27	of	of	ADP
admet-10	75	28	potential	potential	ADJ
admet-10	75	29	toxicity	toxicity	NOUN
admet-10	75	30	.	.	PUNCT
admet-10	76	1	however	however	ADV
admet-10	76	2	,	,	PUNCT
admet-10	76	3	little	little	ADJ
admet-10	76	4	details	detail	NOUN
admet-10	76	5	were	be	AUX
admet-10	76	6	given	give	VERB
admet-10	76	7	in	in	ADP
admet-10	76	8	the	the	DET
admet-10	76	9	guidance	guidance	NOUN
admet-10	76	10	document	document	NOUN
admet-10	76	11	regarding	regard	VERB
admet-10	76	12	the	the	DET
admet-10	76	13	selection	selection	NOUN
admet-10	76	14	of	of	ADP
admet-10	76	15	pad	pad	NOUN
admet-10	76	16	and	and	CCONJ
admet-10	76	17	the	the	DET
admet-10	76	18	strategy	strategy	NOUN
admet-10	76	19	for	for	ADP
admet-10	76	20	reducing	reduce	VERB
admet-10	76	21	the	the	DET
admet-10	76	22	clinical	clinical	ADJ
admet-10	76	23	starting	starting	NOUN
admet-10	76	24	dose	dose	NOUN
admet-10	76	25	.	.	PUNCT
admet-10	77	1	4	4	X
admet-10	77	2	.	.	X
admet-10	78	1	the	the	DET
admet-10	78	2	drug	drug	NOUN
admet-10	78	3	trial	trial	NOUN
admet-10	78	4	that	that	PRON
admet-10	78	5	went	go	VERB
admet-10	78	6	horribly	horribly	ADV
admet-10	78	7	wrong	wrong	ADJ
admet-10	78	8	in	in	ADP
admet-10	78	9	2006	2006	NUM
admet-10	78	10	,	,	PUNCT
admet-10	78	11	a	a	DET
admet-10	78	12	phase	phase	NOUN
admet-10	78	13	i	i	PRON
admet-10	78	14	clinical	clinical	ADJ
admet-10	78	15	trial	trial	NOUN
admet-10	78	16	was	be	AUX
admet-10	78	17	conducted	conduct	VERB
admet-10	78	18	at	at	ADP
admet-10	78	19	northwick	northwick	PROPN
admet-10	78	20	park	park	PROPN
admet-10	78	21	hospital	hospital	NOUN
admet-10	78	22	in	in	ADP
admet-10	78	23	london	london	PROPN
admet-10	78	24	to	to	PART
admet-10	78	25	evaluate	evaluate	VERB
admet-10	78	26	a	a	DET
admet-10	78	27	humanised	humanise	VERB
admet-10	78	28	monoclonal	monoclonal	NOUN
admet-10	78	29	antibody	antibody	NOUN
admet-10	78	30	–	–	PUNCT
admet-10	78	31	a	a	DET
admet-10	78	32	cd28	cd28	PROPN
admet-10	78	33	superagonist	superagonist	NOUN
admet-10	78	34	,	,	PUNCT
admet-10	78	35	also	also	ADV
admet-10	78	36	known	know	VERB
admet-10	78	37	as	as	ADP
admet-10	78	38	tgn1412	tgn1412	NOUN
admet-10	78	39	[	[	X
admet-10	78	40	4	4	NUM
admet-10	78	41	]	]	PUNCT
admet-10	78	42	.	.	PUNCT
admet-10	79	1	tgn1412	tgn1412	PROPN
admet-10	79	2	was	be	AUX
admet-10	79	3	in	in	ADP
admet-10	79	4	development	development	NOUN
admet-10	79	5	for	for	ADP
admet-10	79	6	the	the	DET
admet-10	79	7	treatment	treatment	NOUN
admet-10	79	8	of	of	ADP
admet-10	79	9	b	b	NOUN
admet-10	79	10	cell	cell	NOUN
admet-10	79	11	chronic	chronic	ADJ
admet-10	79	12	lymphocytic	lymphocytic	ADJ
admet-10	79	13	leukaemia	leukaemia	NOUN
admet-10	79	14	,	,	PUNCT
admet-10	79	15	with	with	ADP
admet-10	79	16	the	the	DET
admet-10	79	17	expectation	expectation	NOUN
admet-10	79	18	that	that	SCONJ
admet-10	79	19	it	it	PRON
admet-10	79	20	would	would	AUX
admet-10	79	21	reverse	reverse	VERB
admet-10	79	22	the	the	DET
admet-10	79	23	t	t	NOUN
admet-10	79	24	cell	cell	NOUN
admet-10	79	25	deficiency	deficiency	NOUN
admet-10	79	26	in	in	ADP
admet-10	79	27	this	this	DET
admet-10	79	28	disease	disease	NOUN
admet-10	79	29	,	,	PUNCT
admet-10	79	30	by	by	ADP
admet-10	79	31	activating	activate	VERB
admet-10	79	32	the	the	DET
admet-10	79	33	t	t	NOUN
admet-10	79	34	cell	cell	NOUN
admet-10	79	35	compartment	compartment	NOUN
admet-10	79	36	[	[	X
admet-10	79	37	13	13	NUM
admet-10	79	38	]	]	PUNCT
admet-10	79	39	.	.	PUNCT
admet-10	80	1	soon	soon	ADV
admet-10	80	2	after	after	ADP
admet-10	80	3	the	the	DET
admet-10	80	4	administration	administration	NOUN
admet-10	80	5	of	of	ADP
admet-10	80	6	tgn1412	tgn1412	NOUN
admet-10	80	7	to	to	ADP
admet-10	80	8	6	6	NUM
admet-10	80	9	healthy	healthy	ADJ
admet-10	80	10	volunteers	volunteer	NOUN
admet-10	80	11	,	,	PUNCT
admet-10	80	12	the	the	DET
admet-10	80	13	trial	trial	NOUN
admet-10	80	14	turned	turn	VERB
admet-10	80	15	into	into	ADP
admet-10	80	16	a	a	DET
admet-10	80	17	catastrophe	catastrophe	NOUN
admet-10	80	18	because	because	SCONJ
admet-10	80	19	the	the	DET
admet-10	80	20	treatment	treatment	NOUN
admet-10	80	21	unexpectedly	unexpectedly	ADV
admet-10	80	22	induced	induce	VERB
admet-10	80	23	a	a	DET
admet-10	80	24	rapid	rapid	ADJ
admet-10	80	25	and	and	CCONJ
admet-10	80	26	massive	massive	ADJ
admet-10	80	27	cytokine	cytokine	NOUN
admet-10	80	28	storm	storm	NOUN
admet-10	80	29	that	that	PRON
admet-10	80	30	caused	cause	VERB
admet-10	80	31	severe	severe	ADJ
admet-10	80	32	and	and	CCONJ
admet-10	80	33	lifethreatening	lifethreatene	VERB
admet-10	80	34	adverse	adverse	ADJ
admet-10	80	35	effects	effect	NOUN
admet-10	80	36	in	in	ADP
admet-10	80	37	all	all	DET
admet-10	80	38	six	six	NUM
admet-10	80	39	volunteers	volunteer	NOUN
admet-10	80	40	.	.	PUNCT
admet-10	81	1	six	six	NUM
admet-10	81	2	volunteers	volunteer	NOUN
admet-10	81	3	were	be	AUX
admet-10	81	4	hospitalised	hospitalise	VERB
admet-10	81	5	and	and	CCONJ
admet-10	81	6	suffered	suffer	VERB
admet-10	81	7	from	from	ADP
admet-10	81	8	multiple	multiple	ADJ
admet-10	81	9	organ	organ	NOUN
admet-10	81	10	dysfunction	dysfunction	NOUN
admet-10	81	11	[	[	X
admet-10	81	12	4	4	NUM
admet-10	81	13	]	]	PUNCT
admet-10	81	14	.	.	PUNCT
admet-10	82	1	the	the	DET
admet-10	82	2	drug	drug	NOUN
admet-10	82	3	was	be	AUX
admet-10	82	4	immediately	immediately	ADV
admet-10	82	5	withdrawn	withdraw	VERB
admet-10	82	6	from	from	ADP
admet-10	82	7	development	development	NOUN
admet-10	82	8	.	.	PUNCT
admet-10	83	1	extensive	extensive	ADJ
admet-10	83	2	studies	study	NOUN
admet-10	83	3	have	have	AUX
admet-10	83	4	been	be	AUX
admet-10	83	5	carried	carry	VERB
admet-10	83	6	out	out	ADP
admet-10	83	7	to	to	PART
admet-10	83	8	investigate	investigate	VERB
admet-10	83	9	the	the	DET
admet-10	83	10	cause	cause	NOUN
admet-10	83	11	of	of	ADP
admet-10	83	12	this	this	DET
admet-10	83	13	adverse	adverse	ADJ
admet-10	83	14	side	side	NOUN
admet-10	83	15	effect	effect	NOUN
admet-10	83	16	in	in	ADP
admet-10	83	17	humans	human	NOUN
admet-10	83	18	[	[	X
admet-10	83	19	14	14	NUM
admet-10	83	20	-	-	SYM
admet-10	83	21	16	16	NUM
admet-10	83	22	]	]	PUNCT
admet-10	83	23	.	.	PUNCT
admet-10	84	1	prior	prior	ADV
admet-10	84	2	to	to	ADP
admet-10	84	3	the	the	DET
admet-10	84	4	clinical	clinical	ADJ
admet-10	84	5	trial	trial	NOUN
admet-10	84	6	,	,	PUNCT
admet-10	84	7	tgn1412	tgn1412	NOUN
admet-10	84	8	was	be	AUX
admet-10	84	9	tested	test	VERB
admet-10	84	10	in	in	ADP
admet-10	84	11	preclinical	preclinical	ADJ
admet-10	84	12	species	specie	NOUN
admet-10	84	13	for	for	ADP
admet-10	84	14	toxicology	toxicology	NOUN
admet-10	84	15	studies	study	NOUN
admet-10	84	16	and	and	CCONJ
admet-10	84	17	did	do	AUX
admet-10	84	18	not	not	PART
admet-10	84	19	show	show	VERB
admet-10	84	20	any	any	DET
admet-10	84	21	obvious	obvious	ADJ
admet-10	84	22	adverse	adverse	ADJ
admet-10	84	23	effects	effect	NOUN
admet-10	84	24	[	[	X
admet-10	84	25	14	14	NUM
admet-10	84	26	]	]	PUNCT
admet-10	84	27	.	.	PUNCT
admet-10	85	1	there	there	PRON
admet-10	85	2	is	be	VERB
admet-10	85	3	still	still	ADV
admet-10	85	4	lack	lack	NOUN
admet-10	85	5	of	of	ADP
admet-10	85	6	evidence	evidence	NOUN
admet-10	85	7	to	to	PART
admet-10	85	8	explain	explain	VERB
admet-10	85	9	why	why	SCONJ
admet-10	85	10	tgn1412	tgn1412	NOUN
admet-10	85	11	did	do	AUX
admet-10	85	12	not	not	PART
admet-10	85	13	stimulate	stimulate	VERB
admet-10	85	14	the	the	DET
admet-10	85	15	profound	profound	ADJ
admet-10	85	16	cytokine	cytokine	NOUN
admet-10	85	17	release	release	NOUN
admet-10	85	18	in	in	ADP
admet-10	85	19	vitro	vitro	NOUN
admet-10	85	20	or	or	CCONJ
admet-10	85	21	in	in	ADP
admet-10	85	22	vivo	vivo	NOUN
admet-10	85	23	in	in	ADP
admet-10	85	24	preclinical	preclinical	ADJ
admet-10	85	25	species	specie	NOUN
admet-10	85	26	used	use	VERB
admet-10	85	27	in	in	ADP
admet-10	85	28	safety	safety	NOUN
admet-10	85	29	testing	testing	NOUN
admet-10	85	30	.	.	PUNCT
admet-10	86	1	the	the	DET
admet-10	86	2	underlying	underlie	VERB
admet-10	86	3	molecular	molecular	ADJ
admet-10	86	4	mechanisms	mechanism	NOUN
admet-10	86	5	leading	lead	VERB
admet-10	86	6	to	to	ADP
admet-10	86	7	the	the	DET
admet-10	86	8	adverse	adverse	ADJ
admet-10	86	9	reaction	reaction	NOUN
admet-10	86	10	in	in	ADP
admet-10	86	11	humans	human	NOUN
admet-10	86	12	are	be	AUX
admet-10	86	13	not	not	PART
admet-10	86	14	yet	yet	ADV
admet-10	86	15	fully	fully	ADV
admet-10	86	16	understood	understand	VERB
admet-10	86	17	.	.	PUNCT
admet-10	87	1	it	it	PRON
admet-10	87	2	is	be	AUX
admet-10	87	3	plausible	plausible	ADJ
admet-10	87	4	that	that	SCONJ
admet-10	87	5	a	a	DET
admet-10	87	6	species	species	NOUN
admet-10	87	7	difference	difference	NOUN
admet-10	87	8	in	in	ADP
admet-10	87	9	the	the	DET
admet-10	87	10	organisation	organisation	NOUN
admet-10	87	11	and	and	CCONJ
admet-10	87	12	regulation	regulation	NOUN
admet-10	87	13	of	of	ADP
admet-10	87	14	t	t	NOUN
admet-10	87	15	cell	cell	NOUN
admet-10	87	16	responses	response	NOUN
admet-10	87	17	is	be	AUX
admet-10	87	18	responsible	responsible	ADJ
admet-10	87	19	for	for	ADP
admet-10	87	20	this	this	DET
admet-10	87	21	disparate	disparate	ADJ
admet-10	87	22	immunopharmacology	immunopharmacology	NOUN
admet-10	88	1	[	[	X
admet-10	88	2	17,18	17,18	X
admet-10	88	3	]	]	X
admet-10	88	4	.	.	PUNCT
admet-10	89	1	nevertheless	nevertheless	ADV
admet-10	89	2	,	,	PUNCT
admet-10	89	3	the	the	DET
admet-10	89	4	tgn1412	tgn1412	NOUN
admet-10	89	5	study	study	NOUN
admet-10	89	6	was	be	AUX
admet-10	89	7	the	the	DET
admet-10	89	8	first	first	ADJ
admet-10	89	9	trial	trial	NOUN
admet-10	89	10	of	of	ADP
admet-10	89	11	this	this	DET
admet-10	89	12	tam	tam	PROPN
admet-10	89	13	admet	admet	PROPN
admet-10	89	14	&	&	CCONJ
admet-10	89	15	dmpk	dmpk	PROPN
admet-10	89	16	1(4	1(4	NUM
admet-10	89	17	)	)	PUNCT
admet-10	89	18	(	(	PUNCT
admet-10	89	19	2013	2013	NUM
admet-10	89	20	)	)	PUNCT
admet-10	89	21	63	63	NUM
admet-10	89	22	-	-	SYM
admet-10	89	23	75	75	NUM
admet-10	89	24	68	68	NUM
admet-10	89	25	type	type	NOUN
admet-10	89	26	of	of	ADP
admet-10	89	27	compound	compound	NOUN
admet-10	89	28	in	in	ADP
admet-10	89	29	human	human	NOUN
admet-10	89	30	at	at	ADP
admet-10	89	31	the	the	DET
admet-10	89	32	time	time	NOUN
admet-10	89	33	and	and	CCONJ
admet-10	89	34	a	a	DET
admet-10	89	35	small	small	ADJ
admet-10	89	36	amount	amount	NOUN
admet-10	89	37	of	of	ADP
admet-10	89	38	published	publish	VERB
admet-10	89	39	data	datum	NOUN
admet-10	89	40	were	be	AUX
admet-10	89	41	available	available	ADJ
admet-10	89	42	before	before	ADP
admet-10	89	43	the	the	DET
admet-10	89	44	clinical	clinical	ADJ
admet-10	89	45	investigation	investigation	NOUN
admet-10	89	46	.	.	PUNCT
admet-10	90	1	similar	similar	ADJ
admet-10	90	2	clinical	clinical	ADJ
admet-10	90	3	trials	trial	NOUN
admet-10	90	4	of	of	ADP
admet-10	90	5	antibodies	antibody	NOUN
admet-10	90	6	against	against	ADP
admet-10	90	7	t	t	NOUN
admet-10	90	8	cell	cell	NOUN
admet-10	90	9	antigens	antigen	NOUN
admet-10	90	10	had	have	AUX
admet-10	90	11	already	already	ADV
admet-10	90	12	shown	show	VERB
admet-10	90	13	toxic	toxic	ADJ
admet-10	90	14	effects	effect	NOUN
admet-10	90	15	[	[	X
admet-10	90	16	14	14	NUM
admet-10	90	17	]	]	PUNCT
admet-10	90	18	,	,	PUNCT
admet-10	90	19	suggesting	suggest	VERB
admet-10	90	20	that	that	SCONJ
admet-10	90	21	the	the	DET
admet-10	90	22	tgn1412	tgn1412	NOUN
admet-10	90	23	trial	trial	NOUN
admet-10	90	24	would	would	AUX
admet-10	90	25	be	be	AUX
admet-10	90	26	a	a	DET
admet-10	90	27	high	high	ADJ
admet-10	90	28	-	-	PUNCT
admet-10	90	29	risk	risk	NOUN
admet-10	90	30	study	study	NOUN
admet-10	90	31	.	.	PUNCT
admet-10	91	1	in	in	ADP
admet-10	91	2	the	the	DET
admet-10	91	3	tgn1412	tgn1412	NOUN
admet-10	91	4	trial	trial	NOUN
admet-10	91	5	,	,	PUNCT
admet-10	91	6	the	the	DET
admet-10	91	7	calculation	calculation	NOUN
admet-10	91	8	of	of	ADP
admet-10	91	9	the	the	DET
admet-10	91	10	starting	starting	NOUN
admet-10	91	11	dose	dose	NOUN
admet-10	91	12	was	be	AUX
admet-10	91	13	based	base	VERB
admet-10	91	14	on	on	ADP
admet-10	91	15	the	the	DET
admet-10	91	16	noael	noael	PROPN
admet-10	91	17	approach	approach	NOUN
admet-10	91	18	(	(	PUNCT
admet-10	91	19	section	section	NOUN
admet-10	91	20	3	3	NUM
admet-10	91	21	)	)	PUNCT
admet-10	91	22	.	.	PUNCT
admet-10	92	1	a	a	DET
admet-10	92	2	starting	starting	NOUN
admet-10	92	3	dose	dose	NOUN
admet-10	92	4	of	of	ADP
admet-10	92	5	0.1	0.1	NUM
admet-10	92	6	mg	mg	PROPN
admet-10	92	7	/	/	SYM
admet-10	92	8	kg	kg	PROPN
admet-10	92	9	was	be	AUX
admet-10	92	10	selected	select	VERB
admet-10	92	11	,	,	PUNCT
admet-10	92	12	which	which	PRON
admet-10	92	13	corresponded	correspond	VERB
admet-10	92	14	to	to	ADP
admet-10	92	15	160	160	NUM
admet-10	92	16	times	time	NOUN
admet-10	92	17	lower	low	ADJ
admet-10	92	18	than	than	ADP
admet-10	92	19	the	the	DET
admet-10	92	20	he	he	PRON
admet-10	92	21	d	d	PROPN
admet-10	92	22	derived	derive	VERB
admet-10	92	23	from	from	ADP
admet-10	92	24	the	the	DET
admet-10	92	25	cynomolgus	cynomolgus	ADJ
admet-10	92	26	monkey	monkey	NOUN
admet-10	92	27	studies	study	NOUN
admet-10	92	28	(	(	PUNCT
admet-10	92	29	assuming	assume	VERB
admet-10	92	30	this	this	DET
admet-10	92	31	species	specie	NOUN
admet-10	92	32	was	be	AUX
admet-10	92	33	most	most	ADV
admet-10	92	34	predictive	predictive	ADJ
admet-10	92	35	for	for	ADP
admet-10	92	36	human	human	NOUN
admet-10	92	37	)	)	PUNCT
admet-10	92	38	.	.	PUNCT
admet-10	93	1	subsequent	subsequent	ADJ
admet-10	93	2	analysis	analysis	NOUN
admet-10	93	3	by	by	ADP
admet-10	93	4	the	the	DET
admet-10	93	5	expert	expert	ADJ
admet-10	93	6	scientific	scientific	ADJ
admet-10	93	7	group	group	NOUN
admet-10	93	8	reported	report	VERB
admet-10	93	9	that	that	SCONJ
admet-10	93	10	the	the	DET
admet-10	93	11	trial	trial	NOUN
admet-10	93	12	was	be	AUX
admet-10	93	13	conducted	conduct	VERB
admet-10	93	14	according	accord	VERB
admet-10	93	15	to	to	ADP
admet-10	93	16	the	the	DET
admet-10	93	17	medicines	medicine	NOUN
admet-10	93	18	and	and	CCONJ
admet-10	93	19	healthcare	healthcare	NOUN
admet-10	93	20	products	product	NOUN
admet-10	93	21	regulatory	regulatory	ADJ
admet-10	93	22	agency	agency	NOUN
admet-10	93	23	(	(	PUNCT
admet-10	93	24	mhra	mhra	NOUN
admet-10	93	25	)	)	PUNCT
admet-10	93	26	approved	approve	VERB
admet-10	93	27	policy	policy	NOUN
admet-10	93	28	and	and	CCONJ
admet-10	93	29	there	there	PRON
admet-10	93	30	were	be	VERB
admet-10	93	31	no	no	DET
admet-10	93	32	errors	error	NOUN
admet-10	93	33	involved	involve	VERB
admet-10	93	34	in	in	ADP
admet-10	93	35	the	the	DET
admet-10	93	36	manufacture	manufacture	NOUN
admet-10	93	37	of	of	ADP
admet-10	93	38	tgn1412	tgn1412	NOUN
admet-10	93	39	or	or	CCONJ
admet-10	93	40	in	in	ADP
admet-10	93	41	its	its	PRON
admet-10	93	42	formulation	formulation	NOUN
admet-10	93	43	,	,	PUNCT
admet-10	93	44	dilution	dilution	NOUN
admet-10	93	45	or	or	CCONJ
admet-10	93	46	administration	administration	NOUN
admet-10	93	47	to	to	ADP
admet-10	93	48	trial	trial	NOUN
admet-10	93	49	participants	participant	NOUN
admet-10	93	50	[	[	X
admet-10	93	51	4	4	NUM
admet-10	93	52	]	]	PUNCT
admet-10	93	53	.	.	PUNCT
admet-10	94	1	it	it	PRON
admet-10	94	2	was	be	AUX
admet-10	94	3	then	then	ADV
admet-10	94	4	concluded	conclude	VERB
admet-10	94	5	that	that	SCONJ
admet-10	94	6	an	an	DET
admet-10	94	7	unpredicted	unpredicted	ADJ
admet-10	94	8	biological	biological	ADJ
admet-10	94	9	action	action	NOUN
admet-10	94	10	of	of	ADP
admet-10	94	11	the	the	DET
admet-10	94	12	drug	drug	NOUN
admet-10	94	13	in	in	ADP
admet-10	94	14	humans	human	NOUN
admet-10	94	15	was	be	AUX
admet-10	94	16	the	the	DET
admet-10	94	17	most	most	ADV
admet-10	94	18	likely	likely	ADJ
admet-10	94	19	cause	cause	NOUN
admet-10	94	20	of	of	ADP
admet-10	94	21	the	the	DET
admet-10	94	22	adverse	adverse	ADJ
admet-10	94	23	reactions	reaction	NOUN
admet-10	94	24	.	.	PUNCT
admet-10	95	1	however	however	ADV
admet-10	95	2	,	,	PUNCT
admet-10	95	3	it	it	PRON
admet-10	95	4	has	have	AUX
admet-10	95	5	also	also	ADV
admet-10	95	6	been	be	AUX
admet-10	95	7	suggested	suggest	VERB
admet-10	95	8	that	that	SCONJ
admet-10	95	9	the	the	DET
admet-10	95	10	tragic	tragic	ADJ
admet-10	95	11	incident	incident	NOUN
admet-10	95	12	would	would	AUX
admet-10	95	13	have	have	AUX
admet-10	95	14	been	be	AUX
admet-10	95	15	an	an	DET
admet-10	95	16	avoidable	avoidable	ADJ
admet-10	95	17	rather	rather	ADV
admet-10	95	18	than	than	ADP
admet-10	95	19	an	an	DET
admet-10	95	20	unforeseeable	unforeseeable	ADJ
admet-10	95	21	event	event	NOUN
admet-10	95	22	if	if	SCONJ
admet-10	95	23	the	the	DET
admet-10	95	24	clinical	clinical	ADJ
admet-10	95	25	trial	trial	NOUN
admet-10	95	26	had	have	AUX
admet-10	95	27	been	be	AUX
admet-10	95	28	designed	design	VERB
admet-10	95	29	to	to	PART
admet-10	95	30	emphasise	emphasise	VERB
admet-10	95	31	the	the	DET
admet-10	95	32	safety	safety	NOUN
admet-10	95	33	of	of	ADP
admet-10	95	34	the	the	DET
admet-10	95	35	trial	trial	NOUN
admet-10	95	36	participants	participant	NOUN
admet-10	95	37	[	[	X
admet-10	95	38	19	19	NUM
admet-10	95	39	]	]	PUNCT
admet-10	95	40	.	.	PUNCT
admet-10	96	1	instead	instead	ADV
admet-10	96	2	of	of	ADP
admet-10	96	3	using	use	VERB
admet-10	96	4	the	the	DET
admet-10	96	5	noael	noael	PROPN
admet-10	96	6	approach	approach	NOUN
admet-10	96	7	,	,	PUNCT
admet-10	96	8	the	the	DET
admet-10	96	9	report	report	NOUN
admet-10	96	10	also	also	ADV
admet-10	96	11	highlighted	highlight	VERB
admet-10	96	12	the	the	DET
admet-10	96	13	use	use	NOUN
admet-10	96	14	of	of	ADP
admet-10	96	15	mabel	mabel	NOUN
admet-10	96	16	to	to	PART
admet-10	96	17	estimate	estimate	VERB
admet-10	96	18	the	the	DET
admet-10	96	19	fih	fih	NOUN
admet-10	96	20	dose	dose	NOUN
admet-10	96	21	,	,	PUNCT
admet-10	96	22	which	which	PRON
admet-10	96	23	would	would	AUX
admet-10	96	24	result	result	VERB
admet-10	96	25	in	in	ADP
admet-10	96	26	a	a	DET
admet-10	96	27	much	much	ADV
admet-10	96	28	lower	low	ADJ
admet-10	96	29	value	value	NOUN
admet-10	96	30	for	for	ADP
admet-10	96	31	tgn1412	tgn1412	NOUN
admet-10	96	32	–	–	PUNCT
admet-10	96	33	about	about	ADV
admet-10	96	34	20	20	NUM
admet-10	96	35	-	-	NUM
admet-10	96	36	fold	fold	VERB
admet-10	96	37	lower	low	ADJ
admet-10	96	38	than	than	ADP
admet-10	96	39	the	the	DET
admet-10	96	40	dose	dose	NOUN
admet-10	96	41	used	use	VERB
admet-10	96	42	in	in	ADP
admet-10	96	43	the	the	DET
admet-10	96	44	trial	trial	NOUN
admet-10	96	45	.	.	PUNCT
admet-10	97	1	it	it	PRON
admet-10	97	2	may	may	AUX
admet-10	97	3	be	be	AUX
admet-10	97	4	possible	possible	ADJ
admet-10	97	5	that	that	SCONJ
admet-10	97	6	the	the	DET
admet-10	97	7	use	use	NOUN
admet-10	97	8	of	of	ADP
admet-10	97	9	a	a	DET
admet-10	97	10	lower	low	ADJ
admet-10	97	11	initial	initial	ADJ
admet-10	97	12	dose	dose	NOUN
admet-10	97	13	could	could	AUX
admet-10	97	14	avoid	avoid	VERB
admet-10	97	15	the	the	DET
admet-10	97	16	adverse	adverse	ADJ
admet-10	97	17	effect	effect	NOUN
admet-10	97	18	seen	see	VERB
admet-10	97	19	in	in	ADP
admet-10	97	20	the	the	DET
admet-10	97	21	tgn1412	tgn1412	NOUN
admet-10	97	22	trial	trial	NOUN
admet-10	97	23	,	,	PUNCT
admet-10	97	24	but	but	CCONJ
admet-10	97	25	this	this	PRON
admet-10	97	26	is	be	AUX
admet-10	97	27	a	a	DET
admet-10	97	28	hypothesis	hypothesis	NOUN
admet-10	97	29	that	that	SCONJ
admet-10	97	30	one	one	PRON
admet-10	97	31	would	would	AUX
admet-10	97	32	never	never	ADV
admet-10	97	33	have	have	VERB
admet-10	97	34	the	the	DET
admet-10	97	35	opportunity	opportunity	NOUN
admet-10	97	36	to	to	PART
admet-10	97	37	testify	testify	VERB
admet-10	97	38	.	.	PUNCT
admet-10	98	1	nevertheless	nevertheless	ADV
admet-10	98	2	,	,	PUNCT
admet-10	98	3	after	after	ADP
admet-10	98	4	the	the	DET
admet-10	98	5	publication	publication	NOUN
admet-10	98	6	of	of	ADP
admet-10	98	7	the	the	DET
admet-10	98	8	expert	expert	ADJ
admet-10	98	9	scientific	scientific	ADJ
admet-10	98	10	group	group	NOUN
admet-10	98	11	report	report	NOUN
admet-10	98	12	,	,	PUNCT
admet-10	98	13	the	the	DET
admet-10	98	14	emae	emae	NOUN
admet-10	98	15	has	have	AUX
admet-10	98	16	issued	issue	VERB
admet-10	98	17	a	a	DET
admet-10	98	18	guidance	guidance	NOUN
admet-10	98	19	document	document	NOUN
admet-10	98	20	that	that	PRON
admet-10	98	21	endorsed	endorse	VERB
admet-10	98	22	the	the	DET
admet-10	98	23	use	use	NOUN
admet-10	98	24	of	of	ADP
admet-10	98	25	the	the	DET
admet-10	98	26	mabel	mabel	PROPN
admet-10	98	27	approach	approach	NOUN
admet-10	98	28	for	for	ADP
admet-10	98	29	estimating	estimate	VERB
admet-10	98	30	the	the	DET
admet-10	98	31	fih	fih	NOUN
admet-10	98	32	dose	dose	NOUN
admet-10	98	33	,	,	PUNCT
admet-10	98	34	especially	especially	ADV
admet-10	98	35	for	for	ADP
admet-10	98	36	high	high	ADJ
admet-10	98	37	-	-	PUNCT
admet-10	98	38	risk	risk	NOUN
admet-10	98	39	studies	study	NOUN
admet-10	98	40	[	[	X
admet-10	98	41	5	5	NUM
admet-10	98	42	]	]	PUNCT
admet-10	98	43	.	.	PUNCT
admet-10	99	1	in	in	ADP
admet-10	99	2	the	the	DET
admet-10	99	3	next	next	ADJ
admet-10	99	4	session	session	NOUN
admet-10	99	5	,	,	PUNCT
admet-10	99	6	we	we	PRON
admet-10	99	7	will	will	AUX
admet-10	99	8	briefly	briefly	ADV
admet-10	99	9	discuss	discuss	VERB
admet-10	99	10	the	the	DET
admet-10	99	11	emae	emae	PROPN
admet-10	99	12	guideline	guideline	NOUN
admet-10	99	13	that	that	PRON
admet-10	99	14	endorses	endorse	VERB
admet-10	99	15	the	the	DET
admet-10	99	16	mabel	mabel	PROPN
admet-10	99	17	approach	approach	NOUN
admet-10	99	18	for	for	ADP
admet-10	99	19	dose	dose	NOUN
admet-10	99	20	selection	selection	NOUN
admet-10	99	21	.	.	PUNCT
admet-10	100	1	5	5	X
admet-10	100	2	.	.	X
admet-10	100	3	the	the	DET
admet-10	100	4	mabel	mabel	PROPN
admet-10	100	5	approach	approach	NOUN
admet-10	100	6	for	for	ADP
admet-10	100	7	dose	dose	NOUN
admet-10	100	8	selection	selection	NOUN
admet-10	100	9	the	the	DET
admet-10	100	10	emae	emae	PROPN
admet-10	100	11	guideline	guideline	NOUN
admet-10	100	12	identifies	identify	VERB
admet-10	100	13	factors	factor	NOUN
admet-10	100	14	influencing	influence	VERB
admet-10	100	15	risk	risk	NOUN
admet-10	100	16	for	for	ADP
admet-10	100	17	new	new	ADJ
admet-10	100	18	investigational	investigational	ADJ
admet-10	100	19	medicinal	medicinal	ADJ
admet-10	100	20	products	product	NOUN
admet-10	100	21	,	,	PUNCT
admet-10	100	22	which	which	PRON
admet-10	100	23	covers	cover	VERB
admet-10	100	24	the	the	DET
admet-10	100	25	transition	transition	NOUN
admet-10	100	26	from	from	ADP
admet-10	100	27	nonclinical	nonclinical	ADJ
admet-10	100	28	to	to	ADP
admet-10	100	29	early	early	ADJ
admet-10	100	30	clinical	clinical	ADJ
admet-10	100	31	development	development	NOUN
admet-10	101	1	[	[	X
admet-10	101	2	5	5	NUM
admet-10	101	3	]	]	PUNCT
admet-10	101	4	.	.	PUNCT
admet-10	102	1	strategies	strategy	NOUN
admet-10	102	2	for	for	ADP
admet-10	102	3	mitigating	mitigate	VERB
admet-10	102	4	and	and	CCONJ
admet-10	102	5	managing	manage	VERB
admet-10	102	6	risk	risk	NOUN
admet-10	102	7	are	be	AUX
admet-10	102	8	given	give	VERB
admet-10	102	9	.	.	PUNCT
admet-10	103	1	these	these	PRON
admet-10	103	2	include	include	VERB
admet-10	103	3	:	:	PUNCT
admet-10	103	4	the	the	DET
admet-10	103	5	calculation	calculation	NOUN
admet-10	103	6	of	of	ADP
admet-10	103	7	the	the	DET
admet-10	103	8	first	first	ADJ
admet-10	103	9	dose	dose	NOUN
admet-10	103	10	in	in	ADP
admet-10	103	11	humans	human	NOUN
admet-10	103	12	,	,	PUNCT
admet-10	103	13	the	the	DET
admet-10	103	14	subsequent	subsequent	ADJ
admet-10	103	15	dose	dose	NOUN
admet-10	103	16	escalation	escalation	NOUN
admet-10	103	17	,	,	PUNCT
admet-10	103	18	and	and	CCONJ
admet-10	103	19	the	the	DET
admet-10	103	20	conduct	conduct	NOUN
admet-10	103	21	of	of	ADP
admet-10	103	22	the	the	DET
admet-10	103	23	clinical	clinical	ADJ
admet-10	103	24	trial	trial	NOUN
admet-10	103	25	,	,	PUNCT
admet-10	103	26	all	all	PRON
admet-10	103	27	of	of	ADP
admet-10	103	28	which	which	PRON
admet-10	103	29	are	be	AUX
admet-10	103	30	thought	think	VERB
admet-10	103	31	to	to	PART
admet-10	103	32	have	have	AUX
admet-10	103	33	been	be	AUX
admet-10	103	34	triggered	trigger	VERB
admet-10	103	35	by	by	ADP
admet-10	103	36	the	the	DET
admet-10	103	37	tragic	tragic	ADJ
admet-10	103	38	incident	incident	NOUN
admet-10	103	39	of	of	ADP
admet-10	103	40	the	the	DET
admet-10	103	41	tgn1412	tgn1412	NOUN
admet-10	103	42	trial	trial	NOUN
admet-10	103	43	.	.	PUNCT
admet-10	104	1	the	the	DET
admet-10	104	2	guideline	guideline	NOUN
admet-10	104	3	is	be	AUX
admet-10	104	4	supposed	suppose	VERB
admet-10	104	5	to	to	PART
admet-10	104	6	use	use	VERB
admet-10	104	7	in	in	ADP
admet-10	104	8	conjunction	conjunction	NOUN
admet-10	104	9	with	with	ADP
admet-10	104	10	several	several	ADJ
admet-10	104	11	other	other	ADJ
admet-10	104	12	nonclinical	nonclinical	ADJ
admet-10	104	13	and	and	CCONJ
admet-10	104	14	clinical	clinical	ADJ
admet-10	104	15	eu	eu	PROPN
admet-10	104	16	guidelines	guideline	NOUN
admet-10	104	17	.	.	PUNCT
admet-10	105	1	the	the	DET
admet-10	105	2	non	non	ADJ
admet-10	105	3	-	-	ADJ
admet-10	105	4	clinical	clinical	ADJ
admet-10	105	5	safety	safety	NOUN
admet-10	105	6	aspect	aspect	NOUN
admet-10	105	7	is	be	AUX
admet-10	105	8	particularly	particularly	ADV
admet-10	105	9	emphasised	emphasise	VERB
admet-10	105	10	with	with	ADP
admet-10	105	11	reference	reference	NOUN
admet-10	105	12	to	to	ADP
admet-10	105	13	the	the	DET
admet-10	105	14	ich	ich	PROPN
admet-10	105	15	m3	m3	PROPN
admet-10	105	16	(	(	PUNCT
admet-10	105	17	non	non	ADJ
admet-10	105	18	-	-	ADJ
admet-10	105	19	clinical	clinical	ADJ
admet-10	105	20	safety	safety	NOUN
admet-10	105	21	studies	study	NOUN
admet-10	105	22	for	for	ADP
admet-10	105	23	clinical	clinical	ADJ
admet-10	105	24	trials	trial	NOUN
admet-10	105	25	)	)	PUNCT
admet-10	106	1	[	[	X
admet-10	106	2	7	7	X
admet-10	106	3	]	]	PUNCT
admet-10	106	4	and	and	CCONJ
admet-10	106	5	the	the	DET
admet-10	106	6	ich	ich	PROPN
admet-10	106	7	m6	m6	PROPN
admet-10	106	8	(	(	PUNCT
admet-10	106	9	preclinical	preclinical	ADJ
admet-10	106	10	safety	safety	NOUN
admet-10	106	11	evaluation	evaluation	NOUN
admet-10	106	12	of	of	ADP
admet-10	106	13	biotechnology	biotechnology	NOUN
admet-10	106	14	-	-	PUNCT
admet-10	106	15	derived	derive	VERB
admet-10	106	16	pharmaceuticals	pharmaceutical	NOUN
admet-10	106	17	)	)	PUNCT
admet-10	107	1	[	[	X
admet-10	107	2	20	20	NUM
admet-10	107	3	]	]	PUNCT
admet-10	107	4	,	,	PUNCT
admet-10	107	5	and	and	CCONJ
admet-10	107	6	four	four	NUM
admet-10	107	7	other	other	ADJ
admet-10	107	8	related	related	ADJ
admet-10	107	9	guidelines	guideline	NOUN
admet-10	107	10	[	[	X
admet-10	107	11	5	5	NUM
admet-10	107	12	]	]	PUNCT
admet-10	107	13	.	.	PUNCT
admet-10	108	1	here	here	ADV
admet-10	108	2	,	,	PUNCT
admet-10	108	3	we	we	PRON
admet-10	108	4	will	will	AUX
admet-10	108	5	direct	direct	VERB
admet-10	108	6	our	our	PRON
admet-10	108	7	attention	attention	NOUN
admet-10	108	8	to	to	ADP
admet-10	108	9	the	the	DET
admet-10	108	10	estimation	estimation	NOUN
admet-10	108	11	of	of	ADP
admet-10	108	12	the	the	DET
admet-10	108	13	first	first	ADJ
admet-10	108	14	dose	dose	NOUN
admet-10	108	15	in	in	ADP
admet-10	108	16	humans	human	NOUN
admet-10	108	17	.	.	PUNCT
admet-10	109	1	as	as	SCONJ
admet-10	109	2	highlighted	highlight	VERB
admet-10	109	3	above	above	ADV
admet-10	109	4	,	,	PUNCT
admet-10	109	5	risk	risk	NOUN
admet-10	109	6	identification	identification	NOUN
admet-10	109	7	and	and	CCONJ
admet-10	109	8	risk	risk	NOUN
admet-10	109	9	mitigation	mitigation	NOUN
admet-10	109	10	are	be	AUX
admet-10	109	11	the	the	DET
admet-10	109	12	focuses	focus	NOUN
admet-10	109	13	of	of	ADP
admet-10	109	14	this	this	DET
admet-10	109	15	emae	emae	NOUN
admet-10	109	16	guideline	guideline	NOUN
admet-10	109	17	.	.	PUNCT
admet-10	110	1	in	in	ADP
admet-10	110	2	particular	particular	ADJ
admet-10	110	3	,	,	PUNCT
admet-10	110	4	factors	factor	NOUN
admet-10	110	5	of	of	ADP
admet-10	110	6	risk	risk	NOUN
admet-10	110	7	may	may	AUX
admet-10	110	8	be	be	AUX
admet-10	110	9	derived	derive	VERB
admet-10	110	10	from	from	ADP
admet-10	110	11	the	the	DET
admet-10	110	12	lack	lack	NOUN
admet-10	110	13	of	of	ADP
admet-10	110	14	knowledge	knowledge	NOUN
admet-10	110	15	in	in	ADP
admet-10	110	16	the	the	DET
admet-10	110	17	following	follow	VERB
admet-10	110	18	areas	area	NOUN
admet-10	110	19	:	:	PUNCT
admet-10	110	20	(	(	PUNCT
admet-10	110	21	1	1	X
admet-10	110	22	)	)	PUNCT
admet-10	110	23	the	the	DET
admet-10	110	24	mode	mode	NOUN
admet-10	110	25	of	of	ADP
admet-10	110	26	action	action	NOUN
admet-10	110	27	this	this	PRON
admet-10	110	28	refers	refer	VERB
admet-10	110	29	to	to	ADP
admet-10	110	30	the	the	DET
admet-10	110	31	knowledge	knowledge	NOUN
admet-10	110	32	on	on	ADP
admet-10	110	33	the	the	DET
admet-10	110	34	nature	nature	NOUN
admet-10	110	35	and	and	CCONJ
admet-10	110	36	intensity	intensity	NOUN
admet-10	110	37	of	of	ADP
admet-10	110	38	the	the	DET
admet-10	110	39	effect	effect	NOUN
admet-10	110	40	of	of	ADP
admet-10	110	41	the	the	DET
admet-10	110	42	medicinal	medicinal	ADJ
admet-10	110	43	product	product	NOUN
admet-10	110	44	on	on	ADP
admet-10	110	45	the	the	DET
admet-10	110	46	specific	specific	ADJ
admet-10	110	47	target	target	NOUN
admet-10	110	48	and	and	CCONJ
admet-10	110	49	non	non	NOUN
admet-10	110	50	-	-	NOUN
admet-10	110	51	targets	target	NOUN
admet-10	110	52	and	and	CCONJ
admet-10	110	53	subsequent	subsequent	ADJ
admet-10	110	54	mechanisms	mechanism	NOUN
admet-10	110	55	.	.	PUNCT
admet-10	111	1	certain	certain	ADJ
admet-10	111	2	modes	mode	NOUN
admet-10	111	3	of	of	ADP
admet-10	111	4	action	action	NOUN
admet-10	111	5	have	have	AUX
admet-10	111	6	been	be	AUX
admet-10	111	7	identified	identify	VERB
admet-10	111	8	to	to	PART
admet-10	111	9	require	require	VERB
admet-10	111	10	special	special	ADJ
admet-10	111	11	attention	attention	NOUN
admet-10	111	12	,	,	PUNCT
admet-10	111	13	which	which	PRON
admet-10	111	14	include	include	VERB
admet-10	111	15	targets	target	NOUN
admet-10	111	16	that	that	PRON
admet-10	111	17	have	have	VERB
admet-10	111	18	pleiotropic	pleiotropic	ADJ
admet-10	111	19	effects	effect	NOUN
admet-10	111	20	or	or	CCONJ
admet-10	111	21	are	be	AUX
admet-10	111	22	ubiquitously	ubiquitously	ADV
admet-10	111	23	expressed	express	VERB
admet-10	111	24	(	(	PUNCT
admet-10	111	25	e.g.	e.g.	ADV
admet-10	111	26	,	,	PUNCT
admet-10	111	27	as	as	ADV
admet-10	111	28	often	often	ADV
admet-10	111	29	occur	occur	VERB
admet-10	111	30	in	in	ADP
admet-10	111	31	the	the	DET
admet-10	111	32	immune	immune	ADJ
admet-10	111	33	system	system	NOUN
admet-10	111	34	)	)	PUNCT
admet-10	111	35	and	and	CCONJ
admet-10	111	36	those	those	PRON
admet-10	111	37	that	that	PRON
admet-10	111	38	have	have	VERB
admet-10	111	39	a	a	DET
admet-10	111	40	biological	biological	ADJ
admet-10	111	41	cascade	cascade	NOUN
admet-10	111	42	or	or	CCONJ
admet-10	111	43	cytokine	cytokine	NOUN
admet-10	111	44	release	release	NOUN
admet-10	111	45	,	,	PUNCT
admet-10	111	46	including	include	VERB
admet-10	111	47	those	those	PRON
admet-10	111	48	leading	lead	VERB
admet-10	111	49	to	to	ADP
admet-10	111	50	an	an	DET
admet-10	111	51	amplification	amplification	NOUN
admet-10	111	52	of	of	ADP
admet-10	111	53	an	an	DET
admet-10	111	54	effect	effect	NOUN
admet-10	111	55	that	that	PRON
admet-10	111	56	might	might	AUX
admet-10	111	57	not	not	PART
admet-10	111	58	be	be	AUX
admet-10	111	59	sufficiently	sufficiently	ADV
admet-10	111	60	controlled	control	VERB
admet-10	111	61	by	by	ADP
admet-10	111	62	a	a	DET
admet-10	111	63	physiological	physiological	ADJ
admet-10	111	64	feedback	feedback	NOUN
admet-10	111	65	mechanisms	mechanism	NOUN
admet-10	111	66	(	(	PUNCT
admet-10	111	67	e.g.	e.g.	ADV
admet-10	111	68	,	,	PUNCT
admet-10	111	69	in	in	ADP
admet-10	111	70	the	the	DET
admet-10	111	71	immune	immune	ADJ
admet-10	111	72	system	system	NOUN
admet-10	111	73	or	or	CCONJ
admet-10	111	74	blood	blood	NOUN
admet-10	111	75	coagulation	coagulation	NOUN
admet-10	111	76	system	system	NOUN
admet-10	111	77	)	)	PUNCT
admet-10	111	78	.	.	PUNCT
admet-10	112	1	monoclonal	monoclonal	NOUN
admet-10	112	2	antibodies	antibody	NOUN
admet-10	112	3	against	against	ADP
admet-10	112	4	the	the	DET
admet-10	112	5	t	t	NOUN
admet-10	112	6	cell	cell	NOUN
admet-10	112	7	targets	target	NOUN
admet-10	112	8	are	be	AUX
admet-10	112	9	named	name	VERB
admet-10	112	10	as	as	ADP
admet-10	112	11	examples	example	NOUN
admet-10	112	12	of	of	ADP
admet-10	112	13	products	product	NOUN
admet-10	112	14	that	that	PRON
admet-10	112	15	have	have	VERB
admet-10	112	16	this	this	DET
admet-10	112	17	latter	latter	ADJ
admet-10	112	18	type	type	NOUN
admet-10	112	19	of	of	ADP
admet-10	112	20	mode	mode	NOUN
admet-10	112	21	of	of	ADP
admet-10	112	22	action	action	NOUN
admet-10	112	23	,	,	PUNCT
admet-10	112	24	presumably	presumably	ADV
admet-10	112	25	because	because	SCONJ
admet-10	112	26	of	of	ADP
admet-10	112	27	the	the	DET
admet-10	112	28	tgn1412	tgn1412	ADJ
admet-10	112	29	trial	trial	NOUN
admet-10	112	30	(	(	PUNCT
admet-10	112	31	see	see	VERB
admet-10	112	32	section	section	NOUN
admet-10	112	33	4	4	NUM
admet-10	112	34	)	)	PUNCT
admet-10	112	35	.	.	PUNCT
admet-10	113	1	admet	admet	PROPN
admet-10	113	2	&	&	CCONJ
admet-10	113	3	dmpk	dmpk	PROPN
admet-10	113	4	1(4	1(4	NUM
admet-10	113	5	)	)	PUNCT
admet-10	113	6	(	(	PUNCT
admet-10	113	7	2013	2013	NUM
admet-10	113	8	)	)	PUNCT
admet-10	113	9	63	63	NUM
admet-10	113	10	-	-	SYM
admet-10	113	11	75	75	NUM
admet-10	113	12	estimating	estimate	VERB
admet-10	113	13	first	first	ADV
admet-10	113	14	in	in	ADP
admet-10	113	15	human	human	PROPN
admet-10	113	16	dose	dose	NOUN
admet-10	113	17	doi	doi	PROPN
admet-10	113	18	:	:	PUNCT
admet-10	113	19	10.5599	10.5599	NUM
admet-10	113	20	/	/	SYM
admet-10	113	21	admet.1.4.10	admet.1.4.10	ADJ
admet-10	113	22	69	69	NUM
admet-10	113	23	(	(	PUNCT
admet-10	113	24	2	2	NUM
admet-10	113	25	)	)	PUNCT
admet-10	113	26	the	the	DET
admet-10	113	27	nature	nature	NOUN
admet-10	113	28	of	of	ADP
admet-10	113	29	the	the	DET
admet-10	113	30	target	target	NOUN
admet-10	113	31	this	this	PRON
admet-10	113	32	may	may	AUX
admet-10	113	33	include	include	VERB
admet-10	113	34	information	information	NOUN
admet-10	113	35	on	on	ADP
admet-10	113	36	the	the	DET
admet-10	113	37	structure	structure	NOUN
admet-10	113	38	,	,	PUNCT
admet-10	113	39	tissue	tissue	NOUN
admet-10	113	40	distribution	distribution	NOUN
admet-10	113	41	,	,	PUNCT
admet-10	113	42	cell	cell	NOUN
admet-10	113	43	specificity	specificity	NOUN
admet-10	113	44	,	,	PUNCT
admet-10	113	45	disease	disease	NOUN
admet-10	113	46	specificity	specificity	NOUN
admet-10	113	47	,	,	PUNCT
admet-10	113	48	regulation	regulation	NOUN
admet-10	113	49	,	,	PUNCT
admet-10	113	50	polymorphisms	polymorphism	NOUN
admet-10	113	51	,	,	PUNCT
admet-10	113	52	level	level	NOUN
admet-10	113	53	of	of	ADP
admet-10	113	54	expression	expression	NOUN
admet-10	113	55	,	,	PUNCT
admet-10	113	56	and	and	CCONJ
admet-10	113	57	biological	biological	ADJ
admet-10	113	58	function	function	NOUN
admet-10	113	59	of	of	ADP
admet-10	113	60	the	the	DET
admet-10	113	61	human	human	ADJ
admet-10	113	62	target	target	NOUN
admet-10	113	63	,	,	PUNCT
admet-10	113	64	including	include	VERB
admet-10	113	65	downstream	downstream	ADJ
admet-10	113	66	effects	effect	NOUN
admet-10	113	67	,	,	PUNCT
admet-10	113	68	and	and	CCONJ
admet-10	113	69	how	how	SCONJ
admet-10	113	70	it	it	PRON
admet-10	113	71	might	might	AUX
admet-10	113	72	vary	vary	VERB
admet-10	113	73	between	between	ADP
admet-10	113	74	individuals	individual	NOUN
admet-10	113	75	in	in	ADP
admet-10	113	76	different	different	ADJ
admet-10	113	77	populations	population	NOUN
admet-10	113	78	of	of	ADP
admet-10	113	79	healthy	healthy	ADJ
admet-10	113	80	subjects	subject	NOUN
admet-10	113	81	and	and	CCONJ
admet-10	113	82	patients	patient	NOUN
admet-10	113	83	.	.	PUNCT
admet-10	114	1	(	(	PUNCT
admet-10	114	2	3	3	X
admet-10	114	3	)	)	PUNCT
admet-10	114	4	the	the	DET
admet-10	114	5	relevance	relevance	NOUN
admet-10	114	6	of	of	ADP
admet-10	114	7	animal	animal	NOUN
admet-10	114	8	models	model	NOUN
admet-10	114	9	.	.	PUNCT
admet-10	115	1	the	the	DET
admet-10	115	2	available	available	ADJ
admet-10	115	3	animal	animal	NOUN
admet-10	115	4	species	specie	NOUN
admet-10	115	5	should	should	AUX
admet-10	115	6	be	be	AUX
admet-10	115	7	compared	compare	VERB
admet-10	115	8	to	to	ADP
admet-10	115	9	humans	human	NOUN
admet-10	115	10	taking	take	VERB
admet-10	115	11	into	into	ADP
admet-10	115	12	account	account	NOUN
admet-10	115	13	the	the	DET
admet-10	115	14	target	target	NOUN
admet-10	115	15	,	,	PUNCT
admet-10	115	16	its	its	PRON
admet-10	115	17	structural	structural	ADJ
admet-10	115	18	homology	homology	NOUN
admet-10	115	19	,	,	PUNCT
admet-10	115	20	distribution	distribution	NOUN
admet-10	115	21	,	,	PUNCT
admet-10	115	22	signal	signal	ADJ
admet-10	115	23	transduction	transduction	NOUN
admet-10	115	24	pathways	pathway	NOUN
admet-10	115	25	and	and	CCONJ
admet-10	115	26	the	the	DET
admet-10	115	27	nature	nature	NOUN
admet-10	115	28	of	of	ADP
admet-10	115	29	pharmacological	pharmacological	ADJ
admet-10	115	30	effects	effect	NOUN
admet-10	115	31	.	.	PUNCT
admet-10	116	1	where	where	SCONJ
admet-10	116	2	the	the	DET
admet-10	116	3	available	available	ADJ
admet-10	116	4	animal	animal	NOUN
admet-10	116	5	species	specie	NOUN
admet-10	116	6	/	/	SYM
admet-10	116	7	models	model	NOUN
admet-10	116	8	or	or	CCONJ
admet-10	116	9	surrogates	surrogate	NOUN
admet-10	116	10	are	be	AUX
admet-10	116	11	perceived	perceive	VERB
admet-10	116	12	to	to	PART
admet-10	116	13	be	be	AUX
admet-10	116	14	of	of	ADP
admet-10	116	15	questionable	questionable	ADJ
admet-10	116	16	relevance	relevance	NOUN
admet-10	116	17	for	for	ADP
admet-10	116	18	thorough	thorough	ADJ
admet-10	116	19	investigation	investigation	NOUN
admet-10	116	20	of	of	ADP
admet-10	116	21	the	the	DET
admet-10	116	22	pharmacological	pharmacological	ADJ
admet-10	116	23	and	and	CCONJ
admet-10	116	24	toxicological	toxicological	ADJ
admet-10	116	25	effects	effect	NOUN
admet-10	116	26	of	of	ADP
admet-10	116	27	the	the	DET
admet-10	116	28	medicinal	medicinal	ADJ
admet-10	116	29	product	product	NOUN
admet-10	116	30	,	,	PUNCT
admet-10	116	31	this	this	PRON
admet-10	116	32	should	should	AUX
admet-10	116	33	be	be	AUX
admet-10	116	34	considered	consider	VERB
admet-10	116	35	as	as	ADP
admet-10	116	36	adding	add	VERB
admet-10	116	37	to	to	ADP
admet-10	116	38	the	the	DET
admet-10	116	39	risk	risk	NOUN
admet-10	116	40	.	.	PUNCT
admet-10	117	1	the	the	DET
admet-10	117	2	emea	emea	PROPN
admet-10	117	3	guideline	guideline	NOUN
admet-10	117	4	has	have	AUX
admet-10	117	5	pointed	point	VERB
admet-10	117	6	out	out	ADP
admet-10	117	7	that	that	SCONJ
admet-10	117	8	the	the	DET
admet-10	117	9	risk	risk	NOUN
admet-10	117	10	assessment	assessment	NOUN
admet-10	117	11	should	should	AUX
admet-10	117	12	be	be	AUX
admet-10	117	13	performed	perform	VERB
admet-10	117	14	on	on	ADP
admet-10	117	15	a	a	DET
admet-10	117	16	‘	'	PUNCT
admet-10	117	17	‘	'	PUNCT
admet-10	117	18	case	case	NOUN
admet-10	117	19	-	-	PUNCT
admet-10	117	20	by	by	ADP
admet-10	117	21	-	-	PUNCT
admet-10	117	22	case	case	NOUN
admet-10	117	23	’’	’'	PUNCT
admet-10	117	24	basis	basis	NOUN
admet-10	117	25	and	and	CCONJ
admet-10	117	26	that	that	SCONJ
admet-10	117	27	a	a	DET
admet-10	117	28	‘	'	PUNCT
admet-10	117	29	‘	'	PUNCT
admet-10	117	30	weight	weight	NOUN
admet-10	117	31	-	-	PUNCT
admet-10	117	32	of	of	ADP
admet-10	117	33	-	-	PUNCT
admet-10	117	34	evidence	evidence	NOUN
admet-10	117	35	’’	’'	PUNCT
admet-10	117	36	approach	approach	NOUN
admet-10	117	37	should	should	AUX
admet-10	117	38	be	be	AUX
admet-10	117	39	used	use	VERB
admet-10	117	40	.	.	PUNCT
admet-10	118	1	despite	despite	SCONJ
admet-10	118	2	the	the	DET
admet-10	118	3	scope	scope	NOUN
admet-10	118	4	of	of	ADP
admet-10	118	5	the	the	DET
admet-10	118	6	guideline	guideline	NOUN
admet-10	118	7	covering	cover	VERB
admet-10	118	8	both	both	CCONJ
admet-10	118	9	chemical	chemical	ADJ
admet-10	118	10	and	and	CCONJ
admet-10	118	11	biological	biological	ADJ
admet-10	118	12	investigational	investigational	ADJ
admet-10	118	13	medicinal	medicinal	ADJ
admet-10	118	14	products	product	NOUN
admet-10	118	15	,	,	PUNCT
admet-10	118	16	the	the	DET
admet-10	118	17	above	above	ADJ
admet-10	118	18	factors	factor	NOUN
admet-10	118	19	of	of	ADP
admet-10	118	20	risk	risk	NOUN
admet-10	118	21	are	be	AUX
admet-10	118	22	mostly	mostly	ADV
admet-10	118	23	derived	derive	VERB
admet-10	118	24	from	from	ADP
admet-10	118	25	the	the	DET
admet-10	118	26	intended	intend	VERB
admet-10	118	27	pharmacological	pharmacological	ADJ
admet-10	118	28	mechanism	mechanism	NOUN
admet-10	118	29	(	(	PUNCT
admet-10	118	30	rather	rather	ADV
admet-10	118	31	than	than	ADP
admet-10	118	32	from	from	ADP
admet-10	118	33	chemical	chemical	ADJ
admet-10	118	34	mechanisms	mechanism	NOUN
admet-10	118	35	)	)	PUNCT
admet-10	118	36	,	,	PUNCT
admet-10	118	37	which	which	PRON
admet-10	118	38	are	be	AUX
admet-10	118	39	more	more	ADV
admet-10	118	40	relevant	relevant	ADJ
admet-10	118	41	to	to	ADP
admet-10	118	42	the	the	DET
admet-10	118	43	exaggerated	exaggerated	ADJ
admet-10	118	44	“	"	PUNCT
admet-10	118	45	on	on	ADP
admet-10	118	46	-	-	PUNCT
admet-10	118	47	target	target	NOUN
admet-10	118	48	”	"	PUNCT
admet-10	118	49	pharmacology	pharmacology	NOUN
admet-10	118	50	as	as	ADP
admet-10	118	51	the	the	DET
admet-10	118	52	mechanism	mechanism	NOUN
admet-10	118	53	of	of	ADP
admet-10	118	54	toxicity	toxicity	NOUN
admet-10	118	55	for	for	ADP
admet-10	118	56	many	many	ADJ
admet-10	118	57	biologics	biologic	NOUN
admet-10	118	58	.	.	PUNCT
admet-10	119	1	in	in	ADP
admet-10	119	2	the	the	DET
admet-10	119	3	calculation	calculation	NOUN
admet-10	119	4	of	of	ADP
admet-10	119	5	the	the	DET
admet-10	119	6	fih	fih	NOUN
admet-10	119	7	dose	dose	NOUN
admet-10	119	8	,	,	PUNCT
admet-10	119	9	it	it	PRON
admet-10	119	10	has	have	AUX
admet-10	119	11	been	be	AUX
admet-10	119	12	suggested	suggest	VERB
admet-10	119	13	that	that	SCONJ
admet-10	119	14	all	all	PRON
admet-10	119	15	of	of	ADP
admet-10	119	16	the	the	DET
admet-10	119	17	information	information	NOUN
admet-10	119	18	has	have	VERB
admet-10	119	19	to	to	PART
admet-10	119	20	be	be	AUX
admet-10	119	21	taken	take	VERB
admet-10	119	22	into	into	ADP
admet-10	119	23	consideration	consideration	NOUN
admet-10	119	24	for	for	ADP
admet-10	119	25	the	the	DET
admet-10	119	26	dose	dose	NOUN
admet-10	119	27	selection	selection	NOUN
admet-10	119	28	.	.	PUNCT
admet-10	120	1	in	in	ADP
admet-10	120	2	general	general	ADJ
admet-10	120	3	,	,	PUNCT
admet-10	120	4	the	the	DET
admet-10	120	5	noael	noael	PROPN
admet-10	120	6	approach	approach	NOUN
admet-10	120	7	is	be	AUX
admet-10	120	8	still	still	ADV
admet-10	120	9	regarded	regard	VERB
admet-10	120	10	as	as	ADP
admet-10	120	11	the	the	DET
admet-10	120	12	method	method	NOUN
admet-10	120	13	that	that	PRON
admet-10	120	14	gives	give	VERB
admet-10	120	15	the	the	DET
admet-10	120	16	most	most	ADV
admet-10	120	17	important	important	ADJ
admet-10	120	18	information	information	NOUN
admet-10	120	19	.	.	PUNCT
admet-10	121	1	however	however	ADV
admet-10	121	2	,	,	PUNCT
admet-10	121	3	for	for	ADP
admet-10	121	4	investigational	investigational	ADJ
admet-10	121	5	medicinal	medicinal	ADJ
admet-10	121	6	products	product	NOUN
admet-10	121	7	where	where	SCONJ
admet-10	121	8	the	the	DET
admet-10	121	9	above	above	ADJ
admet-10	121	10	risk	risk	NOUN
admet-10	121	11	factors	factor	NOUN
admet-10	121	12	have	have	AUX
admet-10	121	13	been	be	AUX
admet-10	121	14	identified	identify	VERB
admet-10	121	15	,	,	PUNCT
admet-10	121	16	the	the	DET
admet-10	121	17	use	use	NOUN
admet-10	121	18	of	of	ADP
admet-10	121	19	the	the	DET
admet-10	121	20	mabel	mabel	PROPN
admet-10	121	21	approach	approach	NOUN
admet-10	121	22	is	be	AUX
admet-10	121	23	recommended	recommend	VERB
admet-10	121	24	.	.	PUNCT
admet-10	122	1	the	the	DET
admet-10	122	2	calculation	calculation	NOUN
admet-10	122	3	of	of	ADP
admet-10	122	4	mabel	mabel	NOUN
admet-10	122	5	should	should	AUX
admet-10	122	6	use	use	VERB
admet-10	122	7	all	all	PRON
admet-10	122	8	in	in	ADV
admet-10	122	9	vitro	vitro	X
admet-10	122	10	and	and	CCONJ
admet-10	122	11	in	in	ADP
admet-10	122	12	vivo	vivo	ADJ
admet-10	122	13	information	information	NOUN
admet-10	122	14	available	available	ADJ
admet-10	122	15	from	from	ADP
admet-10	122	16	pk	pk	PROPN
admet-10	122	17	/	/	SYM
admet-10	122	18	pd	pd	NOUN
admet-10	122	19	,	,	PUNCT
admet-10	122	20	which	which	PRON
admet-10	122	21	may	may	AUX
admet-10	122	22	include	include	VERB
admet-10	122	23	the	the	DET
admet-10	122	24	following	following	NOUN
admet-10	122	25	:	:	PUNCT
admet-10	122	26	(	(	PUNCT
admet-10	122	27	1	1	X
admet-10	122	28	)	)	PUNCT
admet-10	122	29	target	target	NOUN
admet-10	122	30	binding	bind	VERB
admet-10	122	31	and	and	CCONJ
admet-10	122	32	receptor	receptor	NOUN
admet-10	122	33	occupancy	occupancy	NOUN
admet-10	122	34	studies	study	NOUN
admet-10	122	35	in	in	ADP
admet-10	122	36	vitro	vitro	X
admet-10	122	37	in	in	ADP
admet-10	122	38	target	target	NOUN
admet-10	122	39	cells	cell	NOUN
admet-10	122	40	from	from	ADP
admet-10	122	41	human	human	NOUN
admet-10	122	42	and	and	CCONJ
admet-10	122	43	the	the	DET
admet-10	122	44	relevant	relevant	ADJ
admet-10	122	45	animal	animal	NOUN
admet-10	122	46	species	specie	NOUN
admet-10	122	47	(	(	PUNCT
admet-10	122	48	2	2	NUM
admet-10	122	49	)	)	PUNCT
admet-10	122	50	concentration	concentration	NOUN
admet-10	122	51	-	-	PUNCT
admet-10	122	52	response	response	NOUN
admet-10	122	53	curves	curve	NOUN
admet-10	122	54	in	in	ADP
admet-10	122	55	vitro	vitro	X
admet-10	122	56	in	in	ADP
admet-10	122	57	target	target	NOUN
admet-10	122	58	cells	cell	NOUN
admet-10	122	59	from	from	ADP
admet-10	122	60	human	human	NOUN
admet-10	122	61	and	and	CCONJ
admet-10	122	62	the	the	DET
admet-10	122	63	relevant	relevant	ADJ
admet-10	122	64	animal	animal	NOUN
admet-10	122	65	species	specie	NOUN
admet-10	122	66	and	and	CCONJ
admet-10	122	67	dose	dose	NOUN
admet-10	122	68	/	/	SYM
admet-10	122	69	exposure	exposure	NOUN
admet-10	122	70	-	-	PUNCT
admet-10	122	71	response	response	NOUN
admet-10	122	72	in	in	ADP
admet-10	122	73	vivo	vivo	NOUN
admet-10	122	74	in	in	ADP
admet-10	122	75	the	the	DET
admet-10	122	76	relevant	relevant	ADJ
admet-10	122	77	animal	animal	NOUN
admet-10	122	78	species	specie	NOUN
admet-10	122	79	(	(	PUNCT
admet-10	122	80	3	3	NUM
admet-10	122	81	)	)	PUNCT
admet-10	122	82	exposures	exposure	NOUN
admet-10	122	83	at	at	ADP
admet-10	122	84	pharmacological	pharmacological	ADJ
admet-10	122	85	doses	dose	NOUN
admet-10	122	86	in	in	ADP
admet-10	122	87	the	the	DET
admet-10	122	88	relevant	relevant	ADJ
admet-10	122	89	animal	animal	NOUN
admet-10	122	90	species	specie	NOUN
admet-10	122	91	to	to	PART
admet-10	122	92	further	far	ADV
admet-10	122	93	limit	limit	VERB
admet-10	122	94	the	the	DET
admet-10	122	95	potential	potential	NOUN
admet-10	122	96	for	for	ADP
admet-10	122	97	adverse	adverse	ADJ
admet-10	122	98	reactions	reaction	NOUN
admet-10	122	99	in	in	ADP
admet-10	122	100	humans	human	NOUN
admet-10	122	101	,	,	PUNCT
admet-10	122	102	a	a	DET
admet-10	122	103	safety	safety	NOUN
admet-10	122	104	factor	factor	NOUN
admet-10	122	105	may	may	AUX
admet-10	122	106	be	be	AUX
admet-10	122	107	applied	apply	VERB
admet-10	122	108	in	in	ADP
admet-10	122	109	the	the	DET
admet-10	122	110	calculation	calculation	NOUN
admet-10	122	111	of	of	ADP
admet-10	122	112	the	the	DET
admet-10	122	113	first	first	ADJ
admet-10	122	114	dose	dose	NOUN
admet-10	122	115	in	in	ADP
admet-10	122	116	humans	human	NOUN
admet-10	122	117	from	from	ADP
admet-10	122	118	mabel	mabel	PROPN
admet-10	122	119	.	.	PUNCT
admet-10	123	1	this	this	PRON
admet-10	123	2	should	should	AUX
admet-10	123	3	take	take	VERB
admet-10	123	4	into	into	ADP
admet-10	123	5	account	account	NOUN
admet-10	123	6	the	the	DET
admet-10	123	7	criteria	criterion	NOUN
admet-10	123	8	of	of	ADP
admet-10	123	9	risks	risk	NOUN
admet-10	123	10	such	such	ADJ
admet-10	123	11	as	as	ADP
admet-10	123	12	the	the	DET
admet-10	123	13	novelty	novelty	NOUN
admet-10	123	14	of	of	ADP
admet-10	123	15	the	the	DET
admet-10	123	16	active	active	ADJ
admet-10	123	17	substance	substance	NOUN
admet-10	123	18	,	,	PUNCT
admet-10	123	19	its	its	PRON
admet-10	123	20	biological	biological	ADJ
admet-10	123	21	potency	potency	NOUN
admet-10	123	22	and	and	CCONJ
admet-10	123	23	its	its	PRON
admet-10	123	24	mode	mode	NOUN
admet-10	123	25	of	of	ADP
admet-10	123	26	action	action	NOUN
admet-10	123	27	,	,	PUNCT
admet-10	123	28	the	the	DET
admet-10	123	29	degree	degree	NOUN
admet-10	123	30	of	of	ADP
admet-10	123	31	species	specie	NOUN
admet-10	123	32	specificity	specificity	NOUN
admet-10	123	33	,	,	PUNCT
admet-10	123	34	the	the	DET
admet-10	123	35	shape	shape	NOUN
admet-10	123	36	of	of	ADP
admet-10	123	37	the	the	DET
admet-10	123	38	dose	dose	NOUN
admet-10	123	39	-	-	PUNCT
admet-10	123	40	response	response	NOUN
admet-10	123	41	curve	curve	NOUN
admet-10	123	42	and	and	CCONJ
admet-10	123	43	the	the	DET
admet-10	123	44	degree	degree	NOUN
admet-10	123	45	of	of	ADP
admet-10	123	46	uncertainty	uncertainty	NOUN
admet-10	123	47	in	in	ADP
admet-10	123	48	the	the	DET
admet-10	123	49	calculation	calculation	NOUN
admet-10	123	50	of	of	ADP
admet-10	123	51	the	the	DET
admet-10	123	52	mabel	mabel	NOUN
admet-10	123	53	.	.	PUNCT
admet-10	124	1	in	in	ADP
admet-10	124	2	cases	case	NOUN
admet-10	124	3	where	where	SCONJ
admet-10	124	4	the	the	DET
admet-10	124	5	methods	method	NOUN
admet-10	124	6	of	of	ADP
admet-10	124	7	calculation	calculation	NOUN
admet-10	124	8	(	(	PUNCT
admet-10	124	9	e.g.	e.g.	ADV
admet-10	124	10	noael	noael	PROPN
admet-10	124	11	,	,	PUNCT
admet-10	124	12	mabel	mabel	PROPN
admet-10	124	13	)	)	PUNCT
admet-10	124	14	give	give	VERB
admet-10	124	15	different	different	ADJ
admet-10	124	16	estimations	estimation	NOUN
admet-10	124	17	of	of	ADP
admet-10	124	18	the	the	DET
admet-10	124	19	first	first	ADJ
admet-10	124	20	dose	dose	NOUN
admet-10	124	21	in	in	ADP
admet-10	124	22	man	man	NOUN
admet-10	124	23	,	,	PUNCT
admet-10	124	24	the	the	DET
admet-10	124	25	lowest	low	ADJ
admet-10	124	26	value	value	NOUN
admet-10	124	27	should	should	AUX
admet-10	124	28	be	be	AUX
admet-10	124	29	used	use	VERB
admet-10	124	30	.	.	PUNCT
admet-10	125	1	there	there	PRON
admet-10	125	2	are	be	VERB
admet-10	125	3	challenges	challenge	NOUN
admet-10	125	4	related	relate	VERB
admet-10	125	5	to	to	ADP
admet-10	125	6	the	the	DET
admet-10	125	7	calculation	calculation	NOUN
admet-10	125	8	of	of	ADP
admet-10	125	9	the	the	DET
admet-10	125	10	mabel	mabel	NOUN
admet-10	125	11	.	.	PUNCT
admet-10	126	1	for	for	ADP
admet-10	126	2	example	example	NOUN
admet-10	126	3	,	,	PUNCT
admet-10	126	4	the	the	DET
admet-10	126	5	guideline	guideline	NOUN
admet-10	126	6	does	do	AUX
admet-10	126	7	not	not	PART
admet-10	126	8	provide	provide	VERB
admet-10	126	9	much	much	ADJ
admet-10	126	10	detail	detail	NOUN
admet-10	126	11	on	on	ADP
admet-10	126	12	the	the	DET
admet-10	126	13	criteria	criterion	NOUN
admet-10	126	14	to	to	PART
admet-10	126	15	define	define	VERB
admet-10	126	16	the	the	DET
admet-10	126	17	minimal	minimal	ADJ
admet-10	126	18	biological	biological	ADJ
admet-10	126	19	effect	effect	NOUN
admet-10	126	20	,	,	PUNCT
admet-10	126	21	the	the	DET
admet-10	126	22	recommended	recommend	VERB
admet-10	126	23	value	value	NOUN
admet-10	126	24	for	for	ADP
admet-10	126	25	the	the	DET
admet-10	126	26	safety	safety	NOUN
admet-10	126	27	factor	factor	NOUN
admet-10	126	28	(	(	PUNCT
admet-10	126	29	if	if	SCONJ
admet-10	126	30	applicable	applicable	ADJ
admet-10	126	31	)	)	PUNCT
admet-10	126	32	,	,	PUNCT
admet-10	126	33	or	or	CCONJ
admet-10	126	34	any	any	DET
admet-10	126	35	example	example	NOUN
admet-10	126	36	of	of	ADP
admet-10	126	37	how	how	SCONJ
admet-10	126	38	mabel	mabel	NOUN
admet-10	126	39	could	could	AUX
admet-10	126	40	be	be	AUX
admet-10	126	41	calculated	calculate	VERB
admet-10	126	42	.	.	PUNCT
admet-10	127	1	fortunately	fortunately	ADV
admet-10	127	2	,	,	PUNCT
admet-10	127	3	the	the	DET
admet-10	127	4	expert	expert	ADJ
admet-10	127	5	scientific	scientific	ADJ
admet-10	127	6	group	group	NOUN
admet-10	127	7	report	report	NOUN
admet-10	127	8	has	have	AUX
admet-10	127	9	given	give	VERB
admet-10	127	10	examples	example	NOUN
admet-10	127	11	of	of	ADP
admet-10	127	12	mabel	mabel	PROPN
admet-10	127	13	calculations	calculation	NOUN
admet-10	127	14	for	for	ADP
admet-10	127	15	tgn1412	tgn1412	NOUN
admet-10	127	16	and	and	CCONJ
admet-10	127	17	two	two	NUM
admet-10	127	18	other	other	ADJ
admet-10	127	19	products	product	NOUN
admet-10	127	20	,	,	PUNCT
admet-10	127	21	as	as	ADV
admet-10	127	22	well	well	ADV
admet-10	127	23	as	as	ADP
admet-10	127	24	the	the	DET
admet-10	127	25	calculation	calculation	NOUN
admet-10	127	26	of	of	ADP
admet-10	127	27	mabel	mabel	NOUN
admet-10	127	28	for	for	ADP
admet-10	127	29	tgn1412	tgn1412	NOUN
admet-10	127	30	based	base	VERB
admet-10	127	31	on	on	ADP
admet-10	127	32	receptor	receptor	NOUN
admet-10	127	33	occupancy	occupancy	NOUN
admet-10	128	1	[	[	X
admet-10	128	2	4	4	NUM
admet-10	128	3	]	]	PUNCT
admet-10	128	4	.	.	PUNCT
admet-10	129	1	following	follow	VERB
admet-10	129	2	the	the	DET
admet-10	129	3	publication	publication	NOUN
admet-10	129	4	of	of	ADP
admet-10	129	5	the	the	DET
admet-10	129	6	expert	expert	ADJ
admet-10	129	7	scientific	scientific	ADJ
admet-10	129	8	group	group	NOUN
admet-10	129	9	report	report	NOUN
admet-10	129	10	,	,	PUNCT
admet-10	129	11	other	other	ADJ
admet-10	129	12	papers	paper	NOUN
admet-10	129	13	on	on	ADP
admet-10	129	14	the	the	DET
admet-10	129	15	use	use	NOUN
admet-10	129	16	of	of	ADP
admet-10	129	17	the	the	DET
admet-10	129	18	mabel	mabel	PROPN
admet-10	129	19	approach	approach	NOUN
admet-10	129	20	to	to	PART
admet-10	129	21	estimate	estimate	VERB
admet-10	129	22	the	the	DET
admet-10	129	23	initial	initial	ADJ
admet-10	129	24	dose	dose	NOUN
admet-10	129	25	for	for	ADP
admet-10	129	26	biologics	biologic	NOUN
admet-10	129	27	have	have	AUX
admet-10	129	28	started	start	VERB
admet-10	129	29	to	to	PART
admet-10	129	30	appear	appear	VERB
admet-10	129	31	in	in	ADP
admet-10	129	32	open	open	ADJ
admet-10	129	33	literature	literature	NOUN
admet-10	130	1	[	[	X
admet-10	130	2	21	21	NUM
admet-10	130	3	-	-	SYM
admet-10	130	4	26	26	NUM
admet-10	130	5	]	]	PUNCT
admet-10	130	6	.	.	PUNCT
admet-10	131	1	these	these	PRON
admet-10	131	2	would	would	AUX
admet-10	131	3	undoubtedly	undoubtedly	ADV
admet-10	131	4	serve	serve	VERB
admet-10	131	5	as	as	ADP
admet-10	131	6	examples	example	NOUN
admet-10	131	7	for	for	ADP
admet-10	131	8	clinical	clinical	ADJ
admet-10	131	9	investigators	investigator	NOUN
admet-10	131	10	to	to	PART
admet-10	131	11	select	select	VERB
admet-10	131	12	the	the	DET
admet-10	131	13	fih	fih	NOUN
admet-10	131	14	dose	dose	VERB
admet-10	131	15	with	with	ADP
admet-10	131	16	the	the	DET
admet-10	131	17	mabel	mabel	PROPN
admet-10	131	18	approach	approach	NOUN
admet-10	131	19	.	.	PUNCT
admet-10	132	1	tam	tam	PROPN
admet-10	132	2	admet	admet	PROPN
admet-10	132	3	&	&	CCONJ
admet-10	132	4	dmpk	dmpk	PROPN
admet-10	132	5	1(4	1(4	NUM
admet-10	132	6	)	)	PUNCT
admet-10	132	7	(	(	PUNCT
admet-10	132	8	2013	2013	NUM
admet-10	132	9	)	)	PUNCT
admet-10	132	10	63	63	NUM
admet-10	132	11	-	-	SYM
admet-10	132	12	75	75	NUM
admet-10	132	13	70	70	NUM
admet-10	132	14	6	6	NUM
admet-10	132	15	.	.	PUNCT
admet-10	132	16	initial	initial	ADJ
admet-10	132	17	dose	dose	NOUN
admet-10	132	18	selection	selection	NOUN
admet-10	132	19	for	for	ADP
admet-10	132	20	oncology	oncology	NOUN
admet-10	132	21	agents	agent	NOUN
admet-10	132	22	we	we	PRON
admet-10	132	23	now	now	ADV
admet-10	132	24	turn	turn	VERB
admet-10	132	25	to	to	ADP
admet-10	132	26	the	the	DET
admet-10	132	27	initial	initial	ADJ
admet-10	132	28	dose	dose	NOUN
admet-10	132	29	selection	selection	NOUN
admet-10	132	30	for	for	ADP
admet-10	132	31	anticancer	anticancer	NOUN
admet-10	132	32	drugs	drug	NOUN
admet-10	132	33	.	.	PUNCT
admet-10	133	1	in	in	ADP
admet-10	133	2	2013	2013	NUM
admet-10	133	3	,	,	PUNCT
admet-10	133	4	emae	emae	PROPN
admet-10	133	5	issued	issue	VERB
admet-10	133	6	an	an	DET
admet-10	133	7	updated	update	VERB
admet-10	133	8	guidance	guidance	NOUN
admet-10	133	9	document	document	NOUN
admet-10	133	10	on	on	ADP
admet-10	133	11	the	the	DET
admet-10	133	12	evaluation	evaluation	NOUN
admet-10	133	13	of	of	ADP
admet-10	133	14	anticancer	anticancer	NOUN
admet-10	133	15	medicinal	medicinal	ADJ
admet-10	133	16	products	product	NOUN
admet-10	133	17	in	in	ADP
admet-10	133	18	humans	human	NOUN
admet-10	133	19	[	[	X
admet-10	133	20	27	27	NUM
admet-10	133	21	]	]	PUNCT
admet-10	133	22	.	.	PUNCT
admet-10	134	1	the	the	DET
admet-10	134	2	document	document	NOUN
admet-10	134	3	was	be	AUX
admet-10	134	4	adopted	adopt	VERB
admet-10	134	5	from	from	ADP
admet-10	134	6	early	early	ADJ
admet-10	134	7	guidelines	guideline	NOUN
admet-10	134	8	dating	date	VERB
admet-10	134	9	back	back	ADV
admet-10	134	10	to	to	ADP
admet-10	134	11	1996	1996	NUM
admet-10	134	12	,	,	PUNCT
admet-10	134	13	where	where	SCONJ
admet-10	134	14	the	the	DET
admet-10	134	15	focus	focus	NOUN
admet-10	134	16	was	be	AUX
admet-10	134	17	mainly	mainly	ADV
admet-10	134	18	on	on	ADP
admet-10	134	19	cytotoxic	cytotoxic	ADJ
admet-10	134	20	anticancer	anticancer	NOUN
admet-10	134	21	compounds	compound	NOUN
admet-10	134	22	.	.	PUNCT
admet-10	135	1	in	in	ADP
admet-10	135	2	contrast	contrast	NOUN
admet-10	135	3	to	to	ADP
admet-10	135	4	the	the	DET
admet-10	135	5	previous	previous	ADJ
admet-10	135	6	version	version	NOUN
admet-10	135	7	published	publish	VERB
admet-10	135	8	in	in	ADP
admet-10	135	9	2005	2005	NUM
admet-10	135	10	,	,	PUNCT
admet-10	135	11	the	the	DET
admet-10	135	12	guideline	guideline	NOUN
admet-10	135	13	highlighted	highlight	VERB
admet-10	135	14	the	the	DET
admet-10	135	15	importance	importance	NOUN
admet-10	135	16	of	of	ADP
admet-10	135	17	the	the	DET
admet-10	135	18	exploratory	exploratory	ADJ
admet-10	135	19	clinical	clinical	ADJ
admet-10	135	20	(	(	PUNCT
admet-10	135	21	phase	phase	NOUN
admet-10	135	22	1/2	1/2	NUM
admet-10	135	23	)	)	PUNCT
admet-10	135	24	studies	study	NOUN
admet-10	135	25	to	to	PART
admet-10	135	26	identify	identify	VERB
admet-10	135	27	the	the	DET
admet-10	135	28	most	most	ADV
admet-10	135	29	appropriate	appropriate	ADJ
admet-10	135	30	target	target	NOUN
admet-10	135	31	population	population	NOUN
admet-10	135	32	for	for	ADP
admet-10	135	33	treatment	treatment	NOUN
admet-10	135	34	with	with	ADP
admet-10	135	35	the	the	DET
admet-10	135	36	selected	select	VERB
admet-10	135	37	biomarkers	biomarker	NOUN
admet-10	135	38	,	,	PUNCT
admet-10	135	39	expanded	expand	VERB
admet-10	135	40	the	the	DET
admet-10	135	41	coverage	coverage	NOUN
admet-10	135	42	on	on	ADP
admet-10	135	43	confirmatory	confirmatory	NOUN
admet-10	135	44	trial	trial	NOUN
admet-10	135	45	(	(	PUNCT
admet-10	135	46	phase	phase	NOUN
admet-10	135	47	3	3	NUM
admet-10	135	48	study	study	NOUN
admet-10	135	49	)	)	PUNCT
admet-10	135	50	,	,	PUNCT
admet-10	135	51	and	and	CCONJ
admet-10	135	52	emphasised	emphasise	VERB
admet-10	135	53	the	the	DET
admet-10	135	54	importance	importance	NOUN
admet-10	135	55	of	of	ADP
admet-10	135	56	understanding	understand	VERB
admet-10	135	57	the	the	DET
admet-10	135	58	pharmacokinetics	pharmacokinetic	NOUN
admet-10	135	59	,	,	PUNCT
admet-10	135	60	particularly	particularly	ADV
admet-10	135	61	in	in	ADP
admet-10	135	62	the	the	DET
admet-10	135	63	potential	potential	NOUN
admet-10	135	64	of	of	ADP
admet-10	135	65	drug	drug	NOUN
admet-10	135	66	-	-	PUNCT
admet-10	135	67	drug	drug	NOUN
admet-10	135	68	interactions	interaction	NOUN
admet-10	135	69	,	,	PUNCT
admet-10	135	70	and	and	CCONJ
admet-10	135	71	for	for	ADP
admet-10	135	72	patients	patient	NOUN
admet-10	135	73	with	with	ADP
admet-10	135	74	impaired	impaired	ADJ
admet-10	135	75	organ	organ	NOUN
admet-10	135	76	function	function	NOUN
admet-10	135	77	.	.	PUNCT
admet-10	136	1	the	the	DET
admet-10	136	2	use	use	NOUN
admet-10	136	3	of	of	ADP
admet-10	136	4	pk	pk	NOUN
admet-10	136	5	/	/	SYM
admet-10	136	6	pd	pd	NOUN
admet-10	136	7	analysis	analysis	NOUN
admet-10	136	8	supported	support	VERB
admet-10	136	9	by	by	ADP
admet-10	136	10	biomarkers	biomarker	NOUN
admet-10	136	11	and	and	CCONJ
admet-10	136	12	clinical	clinical	ADJ
admet-10	136	13	markers	marker	NOUN
admet-10	136	14	data	datum	NOUN
admet-10	136	15	in	in	ADP
admet-10	136	16	phase	phase	NOUN
admet-10	136	17	2/3	2/3	NUM
admet-10	136	18	studies	study	NOUN
admet-10	136	19	has	have	AUX
admet-10	136	20	been	be	AUX
admet-10	136	21	particularly	particularly	ADV
admet-10	136	22	encouraged	encourage	VERB
admet-10	136	23	.	.	PUNCT
admet-10	137	1	the	the	DET
admet-10	137	2	emea	emea	PROPN
admet-10	137	3	guideline	guideline	NOUN
admet-10	137	4	loosely	loosely	ADV
admet-10	137	5	classified	classify	VERB
admet-10	137	6	anticancer	anticancer	NOUN
admet-10	137	7	drugs	drug	NOUN
admet-10	137	8	as	as	ADP
admet-10	137	9	cytotoxic	cytotoxic	ADJ
admet-10	137	10	and	and	CCONJ
admet-10	137	11	non	non	ADJ
admet-10	137	12	-	-	ADJ
admet-10	137	13	cytotoxic	cytotoxic	ADJ
admet-10	137	14	[	[	X
admet-10	137	15	27	27	NUM
admet-10	137	16	]	]	PUNCT
admet-10	137	17	.	.	PUNCT
admet-10	138	1	cytotoxic	cytotoxic	ADJ
admet-10	138	2	compounds	compound	NOUN
admet-10	138	3	elicit	elicit	VERB
admet-10	138	4	the	the	DET
admet-10	138	5	anticancer	anticancer	NOUN
admet-10	138	6	effects	effect	NOUN
admet-10	138	7	by	by	ADP
admet-10	138	8	means	mean	NOUN
admet-10	138	9	of	of	ADP
admet-10	138	10	killing	kill	VERB
admet-10	138	11	or	or	CCONJ
admet-10	138	12	preventing	prevent	VERB
admet-10	138	13	the	the	DET
admet-10	138	14	division	division	NOUN
admet-10	138	15	of	of	ADP
admet-10	138	16	cells	cell	NOUN
admet-10	138	17	.	.	PUNCT
admet-10	139	1	the	the	DET
admet-10	139	2	drug	drug	NOUN
admet-10	139	3	action	action	NOUN
admet-10	139	4	is	be	AUX
admet-10	139	5	nonspecific	nonspecific	ADJ
admet-10	139	6	in	in	ADP
admet-10	139	7	targeting	target	VERB
admet-10	139	8	abnormal	abnormal	ADJ
admet-10	139	9	and	and	CCONJ
admet-10	139	10	normal	normal	ADJ
admet-10	139	11	cells	cell	NOUN
admet-10	139	12	,	,	PUNCT
admet-10	139	13	which	which	PRON
admet-10	139	14	is	be	AUX
admet-10	139	15	usually	usually	ADV
admet-10	139	16	linked	link	VERB
admet-10	139	17	with	with	ADP
admet-10	139	18	toxicity	toxicity	NOUN
admet-10	139	19	.	.	PUNCT
admet-10	140	1	classical	classical	ADJ
admet-10	140	2	cytotoxic	cytotoxic	ADJ
admet-10	140	3	chemotherapeutic	chemotherapeutic	ADJ
admet-10	140	4	agents	agent	NOUN
admet-10	140	5	include	include	VERB
admet-10	140	6	:	:	PUNCT
admet-10	140	7	the	the	DET
admet-10	140	8	nitrogen	nitrogen	NOUN
admet-10	140	9	mustard	mustard	NOUN
admet-10	140	10	derivatives	derivative	NOUN
admet-10	140	11	(	(	PUNCT
admet-10	140	12	e.g.	e.g.	ADV
admet-10	140	13	cyclophosphamide	cyclophosphamide	NOUN
admet-10	140	14	,	,	PUNCT
admet-10	140	15	melphalan	melphalan	NOUN
admet-10	140	16	)	)	PUNCT
admet-10	140	17	,	,	PUNCT
admet-10	140	18	antimetabolites	antimetabolite	NOUN
admet-10	140	19	(	(	PUNCT
admet-10	140	20	e.g.	e.g.	ADV
admet-10	140	21	fluorouracil	fluorouracil	NOUN
admet-10	140	22	,	,	PUNCT
admet-10	140	23	methotrexate	methotrexate	NOUN
admet-10	140	24	)	)	PUNCT
admet-10	140	25	,	,	PUNCT
admet-10	140	26	platins	platin	NOUN
admet-10	140	27	(	(	PUNCT
admet-10	140	28	e.g.	e.g.	ADV
admet-10	140	29	cisplatin	cisplatin	NOUN
admet-10	140	30	,	,	PUNCT
admet-10	140	31	oxaliplatin	oxaliplatin	PROPN
admet-10	140	32	)	)	PUNCT
admet-10	140	33	,	,	PUNCT
admet-10	140	34	antimicrotubule	antimicrotubule	NOUN
admet-10	140	35	agents	agent	NOUN
admet-10	140	36	(	(	PUNCT
admet-10	140	37	e.g.	e.g.	ADV
admet-10	140	38	taxol	taxol	PROPN
admet-10	140	39	,	,	PUNCT
admet-10	140	40	vinblastine	vinblastine	NOUN
admet-10	140	41	)	)	PUNCT
admet-10	140	42	and	and	CCONJ
admet-10	140	43	antitumor	antitumor	PROPN
admet-10	140	44	antibiotics	antibiotic	NOUN
admet-10	140	45	(	(	PUNCT
admet-10	140	46	e.g.	e.g.	ADV
admet-10	140	47	doxorubicin	doxorubicin	PROPN
admet-10	140	48	,	,	PUNCT
admet-10	140	49	mitomycin	mitomycin	NOUN
admet-10	140	50	c	c	NOUN
admet-10	140	51	)	)	PUNCT
admet-10	140	52	.	.	PUNCT
admet-10	141	1	as	as	ADP
admet-10	141	2	for	for	ADP
admet-10	141	3	non	non	ADJ
admet-10	141	4	-	-	ADJ
admet-10	141	5	cytotoxic	cytotoxic	ADJ
admet-10	141	6	anticancer	anticancer	NOUN
admet-10	141	7	compounds	compound	NOUN
admet-10	141	8	,	,	PUNCT
admet-10	141	9	this	this	PRON
admet-10	141	10	generally	generally	ADV
admet-10	141	11	refers	refer	VERB
admet-10	141	12	to	to	ADP
admet-10	141	13	molecular	molecular	ADJ
admet-10	141	14	targeted	target	VERB
admet-10	141	15	agents	agent	NOUN
admet-10	141	16	where	where	SCONJ
admet-10	141	17	the	the	DET
admet-10	141	18	drug	drug	NOUN
admet-10	141	19	activity	activity	NOUN
admet-10	141	20	may	may	AUX
admet-10	141	21	connect	connect	VERB
admet-10	141	22	with	with	ADP
admet-10	141	23	novel	novel	ADJ
admet-10	141	24	mechanisms	mechanism	NOUN
admet-10	141	25	such	such	ADJ
admet-10	141	26	as	as	ADP
admet-10	141	27	hormones	hormone	NOUN
admet-10	141	28	,	,	PUNCT
admet-10	141	29	nuclear	nuclear	NOUN
admet-10	141	30	-	-	PUNCT
admet-10	141	31	targeting	target	VERB
admet-10	141	32	,	,	PUNCT
admet-10	141	33	and	and	CCONJ
admet-10	141	34	signaltransduction	signaltransduction	NOUN
admet-10	141	35	targeting	target	VERB
admet-10	141	36	.	.	PUNCT
admet-10	142	1	molecular	molecular	ADJ
admet-10	142	2	targeted	target	VERB
admet-10	142	3	anticancer	anticancer	NOUN
admet-10	142	4	compounds	compound	NOUN
admet-10	142	5	have	have	VERB
admet-10	142	6	the	the	DET
admet-10	142	7	capacity	capacity	NOUN
admet-10	142	8	to	to	PART
admet-10	142	9	modify	modify	VERB
admet-10	142	10	target	target	NOUN
admet-10	142	11	or	or	CCONJ
admet-10	142	12	receptor	receptor	NOUN
admet-10	142	13	function	function	NOUN
admet-10	142	14	in	in	ADP
admet-10	142	15	an	an	DET
admet-10	142	16	ongoing	ongoing	ADJ
admet-10	142	17	manner	manner	NOUN
admet-10	142	18	,	,	PUNCT
admet-10	142	19	and	and	CCONJ
admet-10	142	20	are	be	AUX
admet-10	142	21	usually	usually	ADV
admet-10	142	22	less	less	ADV
admet-10	142	23	toxic	toxic	ADJ
admet-10	142	24	.	.	PUNCT
admet-10	143	1	this	this	DET
admet-10	143	2	kind	kind	NOUN
admet-10	143	3	of	of	ADP
admet-10	143	4	behaviour	behaviour	NOUN
admet-10	143	5	can	can	AUX
admet-10	143	6	be	be	AUX
admet-10	143	7	exemplified	exemplify	VERB
admet-10	143	8	by	by	ADP
admet-10	143	9	the	the	DET
admet-10	143	10	hormone	hormone	NOUN
admet-10	143	11	receptor	receptor	NOUN
admet-10	143	12	-	-	PUNCT
admet-10	143	13	directed	direct	VERB
admet-10	143	14	agents	agent	NOUN
admet-10	143	15	(	(	PUNCT
admet-10	143	16	e.g.	e.g.	ADV
admet-10	143	17	tamoxifen	tamoxifen	NOUN
admet-10	143	18	,	,	PUNCT
admet-10	143	19	anastrozole	anastrozole	NOUN
admet-10	143	20	)	)	PUNCT
admet-10	143	21	and	and	CCONJ
admet-10	143	22	many	many	ADJ
admet-10	143	23	onocogenedirected	onocogenedirecte	VERB
admet-10	143	24	kinase	kinase	PROPN
admet-10	143	25	inhibitors	inhibitor	NOUN
admet-10	143	26	such	such	ADJ
admet-10	143	27	as	as	ADP
admet-10	143	28	gefitinib	gefitinib	NOUN
admet-10	143	29	,	,	PUNCT
admet-10	143	30	erlotinib	erlotinib	NOUN
admet-10	143	31	,	,	PUNCT
admet-10	143	32	imatinib	imatinib	NOUN
admet-10	143	33	,	,	PUNCT
admet-10	143	34	dasatinib	dasatinib	NOUN
admet-10	143	35	,	,	PUNCT
admet-10	143	36	and	and	CCONJ
admet-10	143	37	sorafenib	sorafenib	NOUN
admet-10	143	38	.	.	PUNCT
admet-10	144	1	immune	immune	ADJ
admet-10	144	2	modulators	modulator	NOUN
admet-10	144	3	/	/	SYM
admet-10	144	4	monoclonal	monoclonal	NOUN
admet-10	144	5	antibodies	antibody	NOUN
admet-10	144	6	(	(	PUNCT
admet-10	144	7	e.g.	e.g.	ADV
admet-10	144	8	bevacizumab	bevacizumab	NOUN
admet-10	144	9	,	,	PUNCT
admet-10	144	10	cetuximab	cetuximab	NOUN
admet-10	144	11	)	)	PUNCT
admet-10	144	12	and	and	CCONJ
admet-10	144	13	combination	combination	NOUN
admet-10	144	14	therapy	therapy	NOUN
admet-10	144	15	studies	study	NOUN
admet-10	144	16	are	be	AUX
admet-10	144	17	regarded	regard	VERB
admet-10	144	18	as	as	ADP
admet-10	144	19	two	two	NUM
admet-10	144	20	separated	separate	VERB
admet-10	144	21	categories	category	NOUN
admet-10	144	22	of	of	ADP
admet-10	144	23	anticancer	anticancer	NOUN
admet-10	144	24	products	product	NOUN
admet-10	144	25	in	in	ADP
admet-10	144	26	the	the	DET
admet-10	144	27	guideline	guideline	NOUN
admet-10	144	28	.	.	PUNCT
admet-10	145	1	owing	owe	VERB
admet-10	145	2	to	to	ADP
admet-10	145	3	the	the	DET
admet-10	145	4	differences	difference	NOUN
admet-10	145	5	in	in	ADP
admet-10	145	6	drug	drug	NOUN
admet-10	145	7	actions	action	NOUN
admet-10	145	8	among	among	ADP
admet-10	145	9	the	the	DET
admet-10	145	10	cytotoxics	cytotoxic	NOUN
admet-10	145	11	and	and	CCONJ
admet-10	145	12	non	non	NOUN
admet-10	145	13	-	-	NOUN
admet-10	145	14	cytotoxics	cytotoxic	NOUN
admet-10	145	15	(	(	PUNCT
admet-10	145	16	molecular	molecular	ADJ
admet-10	145	17	targeted	target	VERB
admet-10	145	18	compounds	compound	NOUN
admet-10	145	19	)	)	PUNCT
admet-10	145	20	,	,	PUNCT
admet-10	145	21	and	and	CCONJ
admet-10	145	22	immune	immune	ADJ
admet-10	145	23	modulator	modulator	NOUN
admet-10	145	24	/	/	SYM
admet-10	145	25	monoclonal	monoclonal	NOUN
admet-10	145	26	antibody	antibody	NOUN
admet-10	145	27	and	and	CCONJ
admet-10	145	28	combination	combination	NOUN
admet-10	145	29	therapy	therapy	NOUN
admet-10	145	30	studies	study	NOUN
admet-10	145	31	,	,	PUNCT
admet-10	145	32	the	the	DET
admet-10	145	33	approaches	approach	NOUN
admet-10	145	34	for	for	ADP
admet-10	145	35	initial	initial	ADJ
admet-10	145	36	dose	dose	NOUN
admet-10	145	37	selection	selection	NOUN
admet-10	145	38	are	be	AUX
admet-10	145	39	varied	varied	ADJ
admet-10	145	40	considerably	considerably	ADV
admet-10	145	41	.	.	PUNCT
admet-10	146	1	in	in	ADP
admet-10	146	2	the	the	DET
admet-10	146	3	following	follow	VERB
admet-10	146	4	discussion	discussion	NOUN
admet-10	146	5	,	,	PUNCT
admet-10	146	6	we	we	PRON
admet-10	146	7	will	will	AUX
admet-10	146	8	discuss	discuss	VERB
admet-10	146	9	the	the	DET
admet-10	146	10	fih	fih	NOUN
admet-10	146	11	dose	dose	NOUN
admet-10	146	12	selection	selection	NOUN
admet-10	146	13	approaches	approach	NOUN
admet-10	146	14	for	for	ADP
admet-10	146	15	these	these	DET
admet-10	146	16	four	four	NUM
admet-10	146	17	classes	class	NOUN
admet-10	146	18	of	of	ADP
admet-10	146	19	treatments	treatment	NOUN
admet-10	146	20	.	.	PUNCT
admet-10	147	1	6.1	6.1	NUM
admet-10	147	2	.	.	PUNCT
admet-10	147	3	cytotoxics	cytotoxic	NOUN
admet-10	147	4	the	the	DET
admet-10	147	5	cytotoxic	cytotoxic	ADJ
admet-10	147	6	compounds	compound	NOUN
admet-10	147	7	induce	induce	VERB
admet-10	147	8	irreversible	irreversible	ADJ
admet-10	147	9	lethal	lethal	ADJ
admet-10	147	10	cellular	cellular	ADJ
admet-10	147	11	lesions	lesion	NOUN
admet-10	147	12	following	follow	VERB
admet-10	147	13	short	short	ADJ
admet-10	147	14	-	-	PUNCT
admet-10	147	15	term	term	NOUN
admet-10	147	16	exposure	exposure	NOUN
admet-10	147	17	,	,	PUNCT
admet-10	147	18	which	which	PRON
admet-10	147	19	are	be	AUX
admet-10	147	20	relatively	relatively	ADV
admet-10	147	21	nonselective	nonselective	ADJ
admet-10	147	22	in	in	ADP
admet-10	147	23	terms	term	NOUN
admet-10	147	24	of	of	ADP
admet-10	147	25	their	their	PRON
admet-10	147	26	effects	effect	NOUN
admet-10	147	27	on	on	ADP
admet-10	147	28	tumours	tumour	NOUN
admet-10	147	29	against	against	ADP
admet-10	147	30	normal	normal	ADJ
admet-10	147	31	cells	cell	NOUN
admet-10	147	32	.	.	PUNCT
admet-10	148	1	for	for	ADP
admet-10	148	2	these	these	DET
admet-10	148	3	compounds	compound	NOUN
admet-10	148	4	,	,	PUNCT
admet-10	148	5	toxicity	toxicity	NOUN
admet-10	148	6	and	and	CCONJ
admet-10	148	7	tumour	tumour	NOUN
admet-10	148	8	response	response	NOUN
admet-10	148	9	can	can	AUX
admet-10	148	10	be	be	AUX
admet-10	148	11	regarded	regard	VERB
admet-10	148	12	as	as	ADP
admet-10	148	13	suitable	suitable	ADJ
admet-10	148	14	indicators	indicator	NOUN
admet-10	148	15	of	of	ADP
admet-10	148	16	drug	drug	NOUN
admet-10	148	17	activity	activity	NOUN
admet-10	148	18	[	[	X
admet-10	148	19	27	27	NUM
admet-10	148	20	]	]	PUNCT
admet-10	148	21	.	.	PUNCT
admet-10	149	1	because	because	SCONJ
admet-10	149	2	of	of	ADP
admet-10	149	3	their	their	PRON
admet-10	149	4	inherent	inherent	ADJ
admet-10	149	5	toxicity	toxicity	NOUN
admet-10	149	6	,	,	PUNCT
admet-10	149	7	the	the	DET
admet-10	149	8	clinical	clinical	ADJ
admet-10	149	9	trials	trial	NOUN
admet-10	149	10	of	of	ADP
admet-10	149	11	cytotoxic	cytotoxic	ADJ
admet-10	149	12	agents	agent	NOUN
admet-10	149	13	are	be	AUX
admet-10	149	14	not	not	PART
admet-10	149	15	conducted	conduct	VERB
admet-10	149	16	in	in	ADP
admet-10	149	17	healthy	healthy	ADJ
admet-10	149	18	volunteers	volunteer	NOUN
admet-10	149	19	.	.	PUNCT
admet-10	150	1	instead	instead	ADV
admet-10	150	2	,	,	PUNCT
admet-10	150	3	the	the	DET
admet-10	150	4	fih	fih	NOUN
admet-10	150	5	trial	trial	NOUN
admet-10	150	6	of	of	ADP
admet-10	150	7	these	these	DET
admet-10	150	8	agents	agent	NOUN
admet-10	150	9	usually	usually	ADV
admet-10	150	10	involves	involve	VERB
admet-10	150	11	patients	patient	NOUN
admet-10	150	12	with	with	ADP
admet-10	150	13	advanced	advanced	ADJ
admet-10	150	14	incurable	incurable	ADJ
admet-10	150	15	malignancy	malignancy	NOUN
admet-10	150	16	,	,	PUNCT
admet-10	150	17	which	which	PRON
admet-10	150	18	differs	differ	VERB
admet-10	150	19	considerably	considerably	ADV
admet-10	150	20	from	from	ADP
admet-10	150	21	those	those	PRON
admet-10	150	22	in	in	ADP
admet-10	150	23	most	most	ADJ
admet-10	150	24	other	other	ADJ
admet-10	150	25	therapeutic	therapeutic	ADJ
admet-10	150	26	areas	area	NOUN
admet-10	150	27	.	.	PUNCT
admet-10	151	1	selection	selection	NOUN
admet-10	151	2	of	of	ADP
admet-10	151	3	the	the	DET
admet-10	151	4	starting	starting	NOUN
admet-10	151	5	dose	dose	NOUN
admet-10	151	6	for	for	ADP
admet-10	151	7	the	the	DET
admet-10	151	8	initial	initial	ADJ
admet-10	151	9	phase	phase	NOUN
admet-10	151	10	i	i	PRON
admet-10	151	11	clinical	clinical	ADJ
admet-10	151	12	trial	trial	NOUN
admet-10	151	13	of	of	ADP
admet-10	151	14	cytotoxic	cytotoxic	ADJ
admet-10	151	15	oncology	oncology	NOUN
admet-10	151	16	drug	drug	NOUN
admet-10	151	17	is	be	AUX
admet-10	151	18	based	base	VERB
admet-10	151	19	on	on	ADP
admet-10	151	20	animal	animal	NOUN
admet-10	151	21	toxicology	toxicology	NOUN
admet-10	151	22	studies	study	NOUN
admet-10	151	23	[	[	X
admet-10	151	24	6,27	6,27	NUM
admet-10	151	25	]	]	PUNCT
admet-10	151	26	.	.	PUNCT
admet-10	152	1	these	these	DET
admet-10	152	2	studies	study	NOUN
admet-10	152	3	are	be	AUX
admet-10	152	4	typically	typically	ADV
admet-10	152	5	performed	perform	VERB
admet-10	152	6	in	in	ADP
admet-10	152	7	rodents	rodent	NOUN
admet-10	152	8	(	(	PUNCT
admet-10	152	9	e.g.	e.g.	ADV
admet-10	152	10	mice	mouse	NOUN
admet-10	152	11	/	/	SYM
admet-10	152	12	rats	rat	NOUN
admet-10	152	13	)	)	PUNCT
admet-10	152	14	or	or	CCONJ
admet-10	152	15	other	other	ADJ
admet-10	152	16	non	non	ADJ
admet-10	152	17	-	-	ADJ
admet-10	152	18	rodent	rodent	ADJ
admet-10	152	19	large	large	ADJ
admet-10	152	20	species	specie	NOUN
admet-10	152	21	(	(	PUNCT
admet-10	152	22	e.g.	e.g.	ADV
admet-10	152	23	dogs	dog	NOUN
admet-10	152	24	)	)	PUNCT
admet-10	152	25	.	.	PUNCT
admet-10	153	1	it	it	PRON
admet-10	153	2	has	have	AUX
admet-10	153	3	been	be	AUX
admet-10	153	4	shown	show	VERB
admet-10	153	5	that	that	SCONJ
admet-10	153	6	rodent	rodent	NOUN
admet-10	153	7	-	-	PUNCT
admet-10	153	8	only	only	ADV
admet-10	153	9	toxicity	toxicity	NOUN
admet-10	153	10	study	study	NOUN
admet-10	153	11	(	(	PUNCT
admet-10	153	12	with	with	ADP
admet-10	153	13	mice	mouse	NOUN
admet-10	153	14	and	and	CCONJ
admet-10	153	15	rats	rat	NOUN
admet-10	153	16	)	)	PUNCT
admet-10	153	17	was	be	AUX
admet-10	153	18	sufficiently	sufficiently	ADV
admet-10	153	19	predictive	predictive	ADJ
admet-10	153	20	in	in	ADP
admet-10	153	21	identifying	identify	VERB
admet-10	153	22	the	the	DET
admet-10	153	23	phase	phase	NOUN
admet-10	153	24	i	i	PRON
admet-10	153	25	trial	trial	NOUN
admet-10	153	26	starting	starting	AUX
admet-10	153	27	dose	dose	NOUN
admet-10	153	28	and	and	CCONJ
admet-10	153	29	commonly	commonly	ADV
admet-10	153	30	encountered	encounter	VERB
admet-10	153	31	dose	dose	NOUN
admet-10	153	32	-	-	PUNCT
admet-10	153	33	limited	limit	VERB
admet-10	153	34	toxicities	toxicity	NOUN
admet-10	153	35	[	[	X
admet-10	153	36	28	28	NUM
admet-10	153	37	]	]	PUNCT
admet-10	153	38	.	.	PUNCT
admet-10	154	1	this	this	PRON
admet-10	154	2	suggests	suggest	VERB
admet-10	154	3	that	that	SCONJ
admet-10	154	4	the	the	DET
admet-10	154	5	routine	routine	ADJ
admet-10	154	6	use	use	NOUN
admet-10	154	7	of	of	ADP
admet-10	154	8	a	a	DET
admet-10	154	9	non	non	ADJ
admet-10	154	10	-	-	ADJ
admet-10	154	11	rodent	rodent	ADJ
admet-10	154	12	large	large	ADJ
admet-10	154	13	species	specie	NOUN
admet-10	154	14	in	in	ADP
admet-10	154	15	preclinical	preclinical	ADJ
admet-10	154	16	toxicology	toxicology	NOUN
admet-10	154	17	studies	study	NOUN
admet-10	154	18	prior	prior	ADV
admet-10	154	19	to	to	ADP
admet-10	154	20	initial	initial	ADJ
admet-10	154	21	clinical	clinical	ADJ
admet-10	154	22	trials	trial	NOUN
admet-10	154	23	with	with	ADP
admet-10	154	24	cancer	cancer	NOUN
admet-10	154	25	therapeutics	therapeutic	NOUN
admet-10	154	26	is	be	AUX
admet-10	154	27	not	not	PART
admet-10	154	28	always	always	ADV
admet-10	154	29	necessary	necessary	ADJ
admet-10	154	30	.	.	PUNCT
admet-10	155	1	from	from	ADP
admet-10	155	2	the	the	DET
admet-10	155	3	mice	mouse	NOUN
admet-10	155	4	studies	study	NOUN
admet-10	155	5	,	,	PUNCT
admet-10	155	6	the	the	DET
admet-10	155	7	dose	dose	NOUN
admet-10	155	8	at	at	ADP
admet-10	155	9	which	which	PRON
admet-10	155	10	10	10	NUM
admet-10	155	11	%	%	NOUN
admet-10	155	12	of	of	ADP
admet-10	155	13	the	the	DET
admet-10	155	14	mice	mouse	NOUN
admet-10	155	15	die	die	VERB
admet-10	155	16	(	(	PUNCT
admet-10	155	17	the	the	DET
admet-10	155	18	murine	murine	ADJ
admet-10	155	19	ld10	ld10	PROPN
admet-10	155	20	)	)	PUNCT
admet-10	155	21	is	be	AUX
admet-10	155	22	defined	define	VERB
admet-10	155	23	.	.	PUNCT
admet-10	156	1	one	one	NUM
admet-10	156	2	-	-	PUNCT
admet-10	156	3	tenth	tenth	NOUN
admet-10	156	4	of	of	ADP
admet-10	156	5	this	this	DET
admet-10	156	6	value	value	NOUN
admet-10	156	7	,	,	PUNCT
admet-10	156	8	0.1	0.1	NUM
admet-10	156	9	mld10	mld10	PROPN
admet-10	156	10	,	,	PUNCT
admet-10	156	11	expressed	express	VERB
admet-10	156	12	in	in	ADP
admet-10	156	13	admet	admet	PROPN
admet-10	156	14	&	&	CCONJ
admet-10	156	15	dmpk	dmpk	PROPN
admet-10	156	16	1(4	1(4	NUM
admet-10	156	17	)	)	PUNCT
admet-10	156	18	(	(	PUNCT
admet-10	156	19	2013	2013	NUM
admet-10	156	20	)	)	PUNCT
admet-10	156	21	63	63	NUM
admet-10	156	22	-	-	SYM
admet-10	156	23	75	75	NUM
admet-10	156	24	estimating	estimate	VERB
admet-10	156	25	first	first	ADV
admet-10	156	26	in	in	ADP
admet-10	156	27	human	human	PROPN
admet-10	156	28	dose	dose	NOUN
admet-10	156	29	doi	doi	PROPN
admet-10	156	30	:	:	PUNCT
admet-10	156	31	10.5599	10.5599	NUM
admet-10	156	32	/	/	SYM
admet-10	156	33	admet.1.4.10	admet.1.4.10	ADJ
admet-10	156	34	71	71	NUM
admet-10	156	35	mg	mg	NUM
admet-10	156	36	/	/	SYM
admet-10	156	37	m2	m2	PROPN
admet-10	156	38	,	,	PUNCT
admet-10	156	39	has	have	AUX
admet-10	156	40	been	be	AUX
admet-10	156	41	historically	historically	ADV
admet-10	156	42	regarded	regard	VERB
admet-10	156	43	as	as	ADP
admet-10	156	44	a	a	DET
admet-10	156	45	safe	safe	ADJ
admet-10	156	46	starting	starting	NOUN
admet-10	156	47	dose	dose	NOUN
admet-10	156	48	in	in	ADP
admet-10	156	49	humans	human	NOUN
admet-10	156	50	provided	provide	VERB
admet-10	156	51	that	that	SCONJ
admet-10	156	52	the	the	DET
admet-10	156	53	toxicology	toxicology	NOUN
admet-10	156	54	studies	study	NOUN
admet-10	156	55	in	in	ADP
admet-10	156	56	a	a	DET
admet-10	156	57	second	second	ADJ
admet-10	156	58	species	specie	NOUN
admet-10	156	59	(	(	PUNCT
admet-10	156	60	e.g.	e.g.	ADV
admet-10	156	61	dog	dog	NOUN
admet-10	156	62	)	)	PUNCT
admet-10	156	63	did	do	AUX
admet-10	156	64	not	not	PART
admet-10	156	65	show	show	VERB
admet-10	156	66	serious	serious	ADJ
admet-10	156	67	,	,	PUNCT
admet-10	156	68	irreversible	irreversible	ADJ
admet-10	156	69	toxicity	toxicity	NOUN
admet-10	156	70	and	and	CCONJ
admet-10	156	71	substantial	substantial	ADJ
admet-10	156	72	differences	difference	NOUN
admet-10	156	73	in	in	ADP
admet-10	156	74	the	the	DET
admet-10	156	75	dose	dose	NOUN
admet-10	156	76	–	–	PUNCT
admet-10	156	77	toxicity	toxicity	NOUN
admet-10	156	78	relationship	relationship	NOUN
admet-10	157	1	[	[	X
admet-10	157	2	29	29	NUM
admet-10	157	3	]	]	PUNCT
admet-10	157	4	.	.	PUNCT
admet-10	158	1	if	if	SCONJ
admet-10	158	2	irreversible	irreversible	ADJ
admet-10	158	3	toxicities	toxicity	NOUN
admet-10	158	4	are	be	AUX
admet-10	158	5	produced	produce	VERB
admet-10	158	6	at	at	ADP
admet-10	158	7	the	the	DET
admet-10	158	8	proposed	propose	VERB
admet-10	158	9	starting	starting	NOUN
admet-10	158	10	dose	dose	NOUN
admet-10	158	11	in	in	ADP
admet-10	158	12	non	non	NOUN
admet-10	158	13	-	-	NOUN
admet-10	158	14	rodents	rodent	NOUN
admet-10	158	15	or	or	CCONJ
admet-10	158	16	if	if	SCONJ
admet-10	158	17	the	the	DET
admet-10	158	18	non	non	ADJ
admet-10	158	19	-	-	ADJ
admet-10	158	20	rodent	rodent	ADJ
admet-10	158	21	is	be	AUX
admet-10	158	22	known	know	VERB
admet-10	158	23	to	to	PART
admet-10	158	24	be	be	AUX
admet-10	158	25	a	a	DET
admet-10	158	26	more	more	ADV
admet-10	158	27	appropriate	appropriate	ADJ
admet-10	158	28	model	model	NOUN
admet-10	158	29	,	,	PUNCT
admet-10	158	30	then	then	ADV
admet-10	158	31	the	the	DET
admet-10	158	32	starting	starting	NOUN
admet-10	158	33	dose	dose	NOUN
admet-10	158	34	could	could	AUX
admet-10	158	35	be	be	AUX
admet-10	158	36	based	base	VERB
admet-10	158	37	on	on	ADP
admet-10	158	38	one	one	NUM
admet-10	158	39	-	-	PUNCT
admet-10	158	40	third	third	NOUN
admet-10	158	41	of	of	ADP
admet-10	158	42	the	the	DET
admet-10	158	43	lowest	low	ADJ
admet-10	158	44	dose	dose	NOUN
admet-10	158	45	in	in	ADP
admet-10	158	46	non	non	NOUN
admet-10	158	47	-	-	NOUN
admet-10	158	48	rodents	rodent	NOUN
admet-10	158	49	that	that	PRON
admet-10	158	50	produces	produce	VERB
admet-10	158	51	drug	drug	NOUN
admet-10	158	52	-	-	PUNCT
admet-10	158	53	induced	induce	VERB
admet-10	158	54	pathological	pathological	ADJ
admet-10	158	55	alterations	alteration	NOUN
admet-10	158	56	in	in	ADP
admet-10	158	57	haematological	haematological	ADJ
admet-10	158	58	,	,	PUNCT
admet-10	158	59	clinical	clinical	ADJ
admet-10	158	60	,	,	PUNCT
admet-10	158	61	or	or	CCONJ
admet-10	158	62	morphological	morphological	ADJ
admet-10	158	63	parameters	parameter	NOUN
admet-10	158	64	and	and	CCONJ
admet-10	158	65	which	which	PRON
admet-10	158	66	,	,	PUNCT
admet-10	158	67	when	when	SCONJ
admet-10	158	68	doubled	double	VERB
admet-10	158	69	,	,	PUNCT
admet-10	158	70	produces	produce	VERB
admet-10	158	71	no	no	DET
admet-10	158	72	lethality	lethality	NOUN
admet-10	159	1	[	[	X
admet-10	159	2	11	11	NUM
admet-10	159	3	]	]	PUNCT
admet-10	159	4	.	.	PUNCT
admet-10	160	1	readers	reader	NOUN
admet-10	160	2	are	be	AUX
admet-10	160	3	directed	direct	VERB
admet-10	160	4	to	to	ADP
admet-10	160	5	a	a	DET
admet-10	160	6	literature	literature	NOUN
admet-10	160	7	working	work	VERB
admet-10	160	8	example	example	NOUN
admet-10	160	9	of	of	ADP
admet-10	160	10	designing	design	VERB
admet-10	160	11	the	the	DET
admet-10	160	12	safe	safe	ADJ
admet-10	160	13	starting	starting	NOUN
admet-10	160	14	dose	dose	NOUN
admet-10	160	15	for	for	ADP
admet-10	160	16	a	a	DET
admet-10	160	17	cytotoxic	cytotoxic	ADJ
admet-10	160	18	agent	agent	NOUN
admet-10	160	19	for	for	ADP
admet-10	160	20	further	further	ADJ
admet-10	160	21	methodological	methodological	ADJ
admet-10	160	22	details	detail	NOUN
admet-10	160	23	[	[	X
admet-10	160	24	30	30	NUM
admet-10	160	25	]	]	PUNCT
admet-10	160	26	.	.	PUNCT
admet-10	161	1	however	however	ADV
admet-10	161	2	,	,	PUNCT
admet-10	161	3	ethical	ethical	ADJ
admet-10	161	4	concerns	concern	NOUN
admet-10	161	5	exist	exist	VERB
admet-10	161	6	on	on	ADP
admet-10	161	7	using	use	VERB
admet-10	161	8	excessive	excessive	ADJ
admet-10	161	9	numbers	number	NOUN
admet-10	161	10	of	of	ADP
admet-10	161	11	patients	patient	NOUN
admet-10	161	12	at	at	ADP
admet-10	161	13	sub	sub	ADJ
admet-10	161	14	-	-	ADJ
admet-10	161	15	therapeutic	therapeutic	ADJ
admet-10	161	16	doses	dose	NOUN
admet-10	161	17	of	of	ADP
admet-10	161	18	a	a	DET
admet-10	161	19	new	new	ADJ
admet-10	161	20	cytotoxic	cytotoxic	ADJ
admet-10	161	21	agent	agent	NOUN
admet-10	161	22	to	to	PART
admet-10	161	23	reach	reach	VERB
admet-10	161	24	the	the	DET
admet-10	161	25	maximum	maximum	ADV
admet-10	161	26	-	-	PUNCT
admet-10	161	27	tolerated	tolerate	VERB
admet-10	161	28	dose	dose	PROPN
admet-10	161	29	(	(	PUNCT
admet-10	161	30	mtd	mtd	PROPN
admet-10	161	31	)	)	PUNCT
admet-10	161	32	during	during	ADP
admet-10	161	33	dose	dose	NOUN
admet-10	161	34	escalation	escalation	NOUN
admet-10	161	35	[	[	X
admet-10	161	36	29	29	NUM
admet-10	161	37	]	]	PUNCT
admet-10	161	38	.	.	PUNCT
admet-10	162	1	increasing	increase	VERB
admet-10	162	2	the	the	DET
admet-10	162	3	starting	starting	NOUN
admet-10	162	4	dose	dose	NOUN
admet-10	162	5	and/or	and/or	CCONJ
admet-10	162	6	pursuing	pursue	VERB
admet-10	162	7	a	a	DET
admet-10	162	8	more	more	ADV
admet-10	162	9	aggressive	aggressive	ADJ
admet-10	162	10	dose	dose	NOUN
admet-10	162	11	escalation	escalation	NOUN
admet-10	162	12	schedule	schedule	NOUN
admet-10	162	13	could	could	AUX
admet-10	162	14	potentially	potentially	ADV
admet-10	162	15	reduce	reduce	VERB
admet-10	162	16	the	the	DET
admet-10	162	17	number	number	NOUN
admet-10	162	18	of	of	ADP
admet-10	162	19	patients	patient	NOUN
admet-10	162	20	treated	treat	VERB
admet-10	162	21	at	at	ADP
admet-10	162	22	sub	sub	ADJ
admet-10	162	23	-	-	ADJ
admet-10	162	24	therapeutic	therapeutic	ADJ
admet-10	162	25	doses	dose	NOUN
admet-10	162	26	.	.	PUNCT
admet-10	163	1	on	on	ADP
admet-10	163	2	the	the	DET
admet-10	163	3	other	other	ADJ
admet-10	163	4	hand	hand	NOUN
admet-10	163	5	,	,	PUNCT
admet-10	163	6	it	it	PRON
admet-10	163	7	is	be	AUX
admet-10	163	8	important	important	ADJ
admet-10	163	9	to	to	PART
admet-10	163	10	protect	protect	VERB
admet-10	163	11	patients	patient	NOUN
admet-10	163	12	from	from	ADP
admet-10	163	13	unacceptable	unacceptable	ADJ
admet-10	163	14	risk	risk	NOUN
admet-10	163	15	in	in	ADP
admet-10	163	16	terms	term	NOUN
admet-10	163	17	of	of	ADP
admet-10	163	18	toxicity	toxicity	NOUN
admet-10	163	19	.	.	PUNCT
admet-10	164	1	there	there	PRON
admet-10	164	2	is	be	VERB
admet-10	164	3	a	a	DET
admet-10	164	4	fine	fine	ADJ
admet-10	164	5	balance	balance	NOUN
admet-10	164	6	between	between	ADP
admet-10	164	7	the	the	DET
admet-10	164	8	starting	starting	NOUN
admet-10	164	9	dose	dose	NOUN
admet-10	164	10	selection	selection	NOUN
admet-10	164	11	,	,	PUNCT
admet-10	164	12	escalation	escalation	NOUN
admet-10	164	13	strategy	strategy	NOUN
admet-10	164	14	and	and	CCONJ
admet-10	164	15	patient	patient	ADJ
admet-10	164	16	safety	safety	NOUN
admet-10	164	17	.	.	PUNCT
admet-10	165	1	6.2	6.2	NUM
admet-10	165	2	.	.	PUNCT
admet-10	166	1	non	non	NOUN
admet-10	166	2	-	-	NOUN
admet-10	166	3	cytotoxics	cytotoxic	NOUN
admet-10	166	4	(	(	PUNCT
admet-10	166	5	molecular	molecular	ADJ
admet-10	166	6	targeted	target	VERB
admet-10	166	7	compounds	compound	NOUN
admet-10	166	8	)	)	PUNCT
admet-10	166	9	unlike	unlike	ADP
admet-10	166	10	cytotoxic	cytotoxic	ADJ
admet-10	166	11	drugs	drug	NOUN
admet-10	166	12	,	,	PUNCT
admet-10	166	13	the	the	DET
admet-10	166	14	pharmacological	pharmacological	ADJ
admet-10	166	15	effects	effect	NOUN
admet-10	166	16	of	of	ADP
admet-10	166	17	molecular	molecular	ADJ
admet-10	166	18	targeted	target	VERB
admet-10	166	19	compounds	compound	NOUN
admet-10	166	20	rarely	rarely	ADV
admet-10	166	21	induce	induce	VERB
admet-10	166	22	acute	acute	ADJ
admet-10	166	23	cellular	cellular	ADJ
admet-10	166	24	damage	damage	NOUN
admet-10	166	25	.	.	PUNCT
admet-10	167	1	most	most	ADV
admet-10	167	2	often	often	ADV
admet-10	167	3	,	,	PUNCT
admet-10	167	4	these	these	DET
admet-10	167	5	drugs	drug	NOUN
admet-10	167	6	are	be	AUX
admet-10	167	7	cytostatic	cytostatic	ADJ
admet-10	167	8	,	,	PUNCT
admet-10	167	9	and	and	CCONJ
admet-10	167	10	are	be	AUX
admet-10	167	11	likely	likely	ADJ
admet-10	167	12	to	to	PART
admet-10	167	13	be	be	AUX
admet-10	167	14	more	more	ADV
admet-10	167	15	effective	effective	ADJ
admet-10	167	16	when	when	SCONJ
admet-10	167	17	administered	administer	VERB
admet-10	167	18	continuously	continuously	ADV
admet-10	167	19	.	.	PUNCT
admet-10	168	1	usually	usually	ADV
admet-10	168	2	,	,	PUNCT
admet-10	168	3	molecular	molecular	ADJ
admet-10	168	4	targeted	target	VERB
admet-10	168	5	compounds	compound	NOUN
admet-10	168	6	will	will	AUX
admet-10	168	7	interact	interact	VERB
admet-10	168	8	with	with	ADP
admet-10	168	9	proteins	protein	NOUN
admet-10	168	10	that	that	PRON
admet-10	168	11	are	be	AUX
admet-10	168	12	specific	specific	ADJ
admet-10	168	13	to	to	ADP
admet-10	168	14	tumour	tumour	NOUN
admet-10	168	15	cells	cell	NOUN
admet-10	168	16	or	or	CCONJ
admet-10	168	17	that	that	PRON
admet-10	168	18	are	be	AUX
admet-10	168	19	up	up	ADV
admet-10	168	20	-	-	PUNCT
admet-10	168	21	regulated	regulate	VERB
admet-10	168	22	during	during	ADP
admet-10	168	23	malignant	malignant	ADJ
admet-10	168	24	transformation	transformation	NOUN
admet-10	168	25	.	.	PUNCT
admet-10	169	1	thus	thus	ADV
admet-10	169	2	,	,	PUNCT
admet-10	169	3	they	they	PRON
admet-10	169	4	tend	tend	VERB
admet-10	169	5	to	to	PART
admet-10	169	6	be	be	AUX
admet-10	169	7	more	more	ADV
admet-10	169	8	selective	selective	ADJ
admet-10	169	9	and	and	CCONJ
admet-10	169	10	less	less	ADV
admet-10	169	11	toxic	toxic	ADJ
admet-10	169	12	to	to	ADP
admet-10	169	13	normal	normal	ADJ
admet-10	169	14	tissue	tissue	NOUN
admet-10	169	15	.	.	PUNCT
admet-10	170	1	increasing	increase	VERB
admet-10	170	2	the	the	DET
admet-10	170	3	dose	dose	NOUN
admet-10	170	4	in	in	ADP
admet-10	170	5	a	a	DET
admet-10	170	6	traditional	traditional	ADJ
admet-10	170	7	phase	phase	NOUN
admet-10	170	8	1	1	NUM
admet-10	170	9	trial	trial	NOUN
admet-10	170	10	to	to	ADP
admet-10	170	11	the	the	DET
admet-10	170	12	mtd	mtd	PROPN
admet-10	170	13	may	may	AUX
admet-10	170	14	be	be	AUX
admet-10	170	15	irrelevant	irrelevant	ADJ
admet-10	170	16	for	for	ADP
admet-10	170	17	molecular	molecular	ADJ
admet-10	170	18	targeted	target	VERB
admet-10	170	19	compounds	compound	NOUN
admet-10	170	20	as	as	SCONJ
admet-10	170	21	the	the	DET
admet-10	170	22	maximum	maximum	ADJ
admet-10	170	23	therapeutic	therapeutic	ADJ
admet-10	170	24	effect	effect	NOUN
admet-10	170	25	may	may	AUX
admet-10	170	26	be	be	AUX
admet-10	170	27	achieved	achieve	VERB
admet-10	170	28	at	at	ADP
admet-10	170	29	doses	dose	NOUN
admet-10	170	30	that	that	PRON
admet-10	170	31	are	be	AUX
admet-10	170	32	well	well	ADV
admet-10	170	33	below	below	ADP
admet-10	170	34	the	the	DET
admet-10	170	35	mtd	mtd	PROPN
admet-10	170	36	.	.	PUNCT
admet-10	171	1	in	in	ADP
admet-10	171	2	some	some	DET
admet-10	171	3	situations	situation	NOUN
admet-10	171	4	,	,	PUNCT
admet-10	171	5	it	it	PRON
admet-10	171	6	may	may	AUX
admet-10	171	7	be	be	AUX
admet-10	171	8	difficult	difficult	ADJ
admet-10	171	9	to	to	PART
admet-10	171	10	determine	determine	VERB
admet-10	171	11	the	the	DET
admet-10	171	12	mtd	mtd	NOUN
admet-10	172	1	[	[	X
admet-10	172	2	31	31	NUM
admet-10	172	3	]	]	PUNCT
admet-10	172	4	.	.	PUNCT
admet-10	173	1	as	as	ADP
admet-10	173	2	such	such	ADJ
admet-10	173	3	,	,	PUNCT
admet-10	173	4	the	the	DET
admet-10	173	5	early	early	ADJ
admet-10	173	6	stages	stage	NOUN
admet-10	173	7	of	of	ADP
admet-10	173	8	clinical	clinical	ADJ
admet-10	173	9	drug	drug	NOUN
admet-10	173	10	development	development	NOUN
admet-10	173	11	are	be	AUX
admet-10	173	12	likely	likely	ADJ
admet-10	173	13	to	to	PART
admet-10	173	14	be	be	AUX
admet-10	173	15	more	more	ADV
admet-10	173	16	complex	complex	ADJ
admet-10	173	17	and	and	CCONJ
admet-10	173	18	have	have	VERB
admet-10	173	19	to	to	PART
admet-10	173	20	be	be	AUX
admet-10	173	21	tailored	tailor	VERB
admet-10	173	22	according	accord	VERB
admet-10	173	23	to	to	ADP
admet-10	173	24	the	the	DET
admet-10	173	25	assumed	assumed	ADJ
admet-10	173	26	pharmacology	pharmacology	NOUN
admet-10	173	27	of	of	ADP
admet-10	173	28	the	the	DET
admet-10	173	29	compound	compound	NOUN
admet-10	173	30	as	as	SCONJ
admet-10	173	31	defined	define	VERB
admet-10	173	32	in	in	ADP
admet-10	173	33	preclinical	preclinical	ADJ
admet-10	173	34	studies	study	NOUN
admet-10	173	35	.	.	PUNCT
admet-10	174	1	an	an	DET
admet-10	174	2	early	early	ADJ
admet-10	174	3	assessment	assessment	NOUN
admet-10	174	4	of	of	ADP
admet-10	174	5	anti	anti	ADJ
admet-10	174	6	-	-	ADJ
admet-10	174	7	tumour	tumour	ADJ
admet-10	174	8	activity	activity	NOUN
admet-10	174	9	using	use	VERB
admet-10	174	10	biomarkers	biomarker	NOUN
admet-10	174	11	and	and	CCONJ
admet-10	174	12	pd	pd	PROPN
admet-10	174	13	(	(	PUNCT
admet-10	174	14	e.g.	e.g.	ADV
admet-10	174	15	receptor	receptor	NOUN
admet-10	174	16	binding	bind	VERB
admet-10	174	17	,	,	PUNCT
admet-10	174	18	enzyme	enzyme	NOUN
admet-10	174	19	inhibition	inhibition	NOUN
admet-10	174	20	,	,	PUNCT
admet-10	174	21	downstream	downstream	ADJ
admet-10	174	22	events	event	NOUN
admet-10	174	23	,	,	PUNCT
admet-10	174	24	or	or	CCONJ
admet-10	174	25	sensitive	sensitive	ADJ
admet-10	174	26	imaging	imaging	NOUN
admet-10	174	27	techniques	technique	NOUN
admet-10	174	28	)	)	PUNCT
admet-10	174	29	may	may	AUX
admet-10	174	30	be	be	AUX
admet-10	174	31	required	require	VERB
admet-10	174	32	to	to	PART
admet-10	174	33	help	help	VERB
admet-10	174	34	to	to	PART
admet-10	174	35	define	define	VERB
admet-10	174	36	the	the	DET
admet-10	174	37	dose	dose	NOUN
admet-10	174	38	and	and	CCONJ
admet-10	174	39	schedule	schedule	NOUN
admet-10	174	40	.	.	PUNCT
admet-10	175	1	for	for	ADP
admet-10	175	2	molecular	molecular	ADJ
admet-10	175	3	targeted	target	VERB
admet-10	175	4	compounds	compound	NOUN
admet-10	175	5	,	,	PUNCT
admet-10	175	6	there	there	PRON
admet-10	175	7	does	do	AUX
admet-10	175	8	not	not	PART
admet-10	175	9	appear	appear	VERB
admet-10	175	10	to	to	PART
admet-10	175	11	be	be	AUX
admet-10	175	12	a	a	DET
admet-10	175	13	standardised	standardised	ADJ
admet-10	175	14	approach	approach	NOUN
admet-10	175	15	for	for	ADP
admet-10	175	16	selecting	select	VERB
admet-10	175	17	the	the	DET
admet-10	175	18	fih	fih	NOUN
admet-10	175	19	dose	dose	NOUN
admet-10	175	20	.	.	PUNCT
admet-10	176	1	this	this	PRON
admet-10	176	2	is	be	AUX
admet-10	176	3	not	not	PART
admet-10	176	4	even	even	ADV
admet-10	176	5	mentioned	mention	VERB
admet-10	176	6	in	in	ADP
admet-10	176	7	the	the	DET
admet-10	176	8	emea	emea	PROPN
admet-10	176	9	guideline	guideline	NOUN
admet-10	176	10	[	[	X
admet-10	176	11	27	27	NUM
admet-10	176	12	]	]	PUNCT
admet-10	176	13	.	.	PUNCT
admet-10	177	1	indeed	indeed	ADV
admet-10	177	2	,	,	PUNCT
admet-10	177	3	le	le	X
admet-10	177	4	tourneau	tourneau	PROPN
admet-10	177	5	et	et	PROPN
admet-10	177	6	al	al	PROPN
admet-10	177	7	.	.	PROPN
admet-10	177	8	reported	report	VERB
admet-10	177	9	that	that	SCONJ
admet-10	177	10	there	there	PRON
admet-10	177	11	is	be	VERB
admet-10	177	12	no	no	DET
admet-10	177	13	consensus	consensus	NOUN
admet-10	177	14	on	on	ADP
admet-10	177	15	which	which	PRON
admet-10	177	16	preclinical	preclinical	ADJ
admet-10	177	17	models	model	NOUN
admet-10	177	18	and	and	CCONJ
admet-10	177	19	parameters	parameter	NOUN
admet-10	177	20	should	should	AUX
admet-10	177	21	define	define	VERB
admet-10	177	22	the	the	DET
admet-10	177	23	starting	starting	NOUN
admet-10	177	24	dose	dose	NOUN
admet-10	177	25	for	for	ADP
admet-10	177	26	molecular	molecular	ADJ
admet-10	177	27	targeted	target	VERB
admet-10	177	28	compounds	compound	NOUN
admet-10	177	29	[	[	X
admet-10	177	30	31	31	NUM
admet-10	177	31	]	]	PUNCT
admet-10	177	32	.	.	PUNCT
admet-10	178	1	the	the	DET
admet-10	178	2	authors	author	NOUN
admet-10	178	3	have	have	AUX
admet-10	178	4	analysed	analyse	VERB
admet-10	178	5	81	81	NUM
admet-10	178	6	fih	fih	NOUN
admet-10	178	7	phase	phase	NOUN
admet-10	178	8	i	i	PRON
admet-10	178	9	trials	trial	VERB
admet-10	178	10	that	that	PRON
admet-10	178	11	evaluated	evaluate	VERB
admet-10	178	12	60	60	NUM
admet-10	178	13	different	different	ADJ
admet-10	178	14	molecular	molecular	ADJ
admet-10	178	15	targeted	target	VERB
admet-10	178	16	agents	agent	NOUN
admet-10	178	17	;	;	PUNCT
admet-10	178	18	the	the	DET
admet-10	178	19	data	datum	NOUN
admet-10	178	20	were	be	AUX
admet-10	178	21	taken	take	VERB
admet-10	178	22	from	from	ADP
admet-10	178	23	open	open	ADJ
admet-10	178	24	literature	literature	NOUN
admet-10	178	25	from	from	ADP
admet-10	178	26	1998	1998	NUM
admet-10	178	27	to	to	ADP
admet-10	178	28	2009	2009	NUM
admet-10	178	29	.	.	PUNCT
admet-10	179	1	in	in	ADP
admet-10	179	2	the	the	DET
admet-10	179	3	81	81	NUM
admet-10	179	4	trials	trial	NOUN
admet-10	179	5	,	,	PUNCT
admet-10	179	6	57	57	NUM
admet-10	179	7	of	of	ADP
admet-10	179	8	which	which	PRON
admet-10	179	9	have	have	AUX
admet-10	179	10	clearly	clearly	ADV
admet-10	179	11	specified	specify	VERB
admet-10	179	12	the	the	DET
admet-10	179	13	animal	animal	NOUN
admet-10	179	14	models	model	NOUN
admet-10	179	15	used	use	VERB
admet-10	179	16	to	to	PART
admet-10	179	17	derive	derive	VERB
admet-10	179	18	the	the	DET
admet-10	179	19	starting	starting	NOUN
admet-10	179	20	dose	dose	PROPN
admet-10	179	21	.	.	PUNCT
admet-10	180	1	figure	figure	NOUN
admet-10	180	2	1	1	NUM
admet-10	180	3	shows	show	VERB
admet-10	180	4	the	the	DET
admet-10	180	5	preclinical	preclinical	ADJ
admet-10	180	6	models	model	NOUN
admet-10	180	7	and	and	CCONJ
admet-10	180	8	toxicological	toxicological	ADJ
admet-10	180	9	parameters	parameter	NOUN
admet-10	180	10	used	use	VERB
admet-10	180	11	to	to	PART
admet-10	180	12	derive	derive	VERB
admet-10	180	13	the	the	DET
admet-10	180	14	starting	starting	NOUN
admet-10	180	15	dose	dose	NOUN
admet-10	180	16	of	of	ADP
admet-10	180	17	these	these	DET
admet-10	180	18	57	57	NUM
admet-10	180	19	phase	phase	NOUN
admet-10	180	20	i	i	PRON
admet-10	180	21	clinical	clinical	ADJ
admet-10	180	22	trials	trial	NOUN
admet-10	180	23	of	of	ADP
admet-10	180	24	molecular	molecular	ADJ
admet-10	180	25	targeted	target	VERB
admet-10	180	26	compounds	compound	NOUN
admet-10	180	27	.	.	PUNCT
admet-10	181	1	it	it	PRON
admet-10	181	2	can	can	AUX
admet-10	181	3	be	be	AUX
admet-10	181	4	seen	see	VERB
admet-10	181	5	that	that	SCONJ
admet-10	181	6	the	the	DET
admet-10	181	7	selections	selection	NOUN
admet-10	181	8	of	of	ADP
admet-10	181	9	fih	fih	NOUN
admet-10	181	10	dose	dose	NOUN
admet-10	181	11	were	be	AUX
admet-10	181	12	based	base	VERB
admet-10	181	13	on	on	ADP
admet-10	181	14	diverse	diverse	ADJ
admet-10	181	15	practices	practice	NOUN
admet-10	181	16	using	use	VERB
admet-10	181	17	a	a	DET
admet-10	181	18	variety	variety	NOUN
admet-10	181	19	of	of	ADP
admet-10	181	20	preclinical	preclinical	ADJ
admet-10	181	21	toxicological	toxicological	ADJ
admet-10	181	22	parameters	parameter	NOUN
admet-10	181	23	.	.	PUNCT
admet-10	182	1	nevertheless	nevertheless	ADV
admet-10	182	2	,	,	PUNCT
admet-10	182	3	most	most	ADJ
admet-10	182	4	of	of	ADP
admet-10	182	5	these	these	DET
admet-10	182	6	trials	trial	NOUN
admet-10	182	7	appeared	appear	VERB
admet-10	182	8	to	to	PART
admet-10	182	9	be	be	AUX
admet-10	182	10	safely	safely	ADV
admet-10	182	11	conducted	conduct	VERB
admet-10	182	12	,	,	PUNCT
admet-10	182	13	which	which	PRON
admet-10	182	14	is	be	AUX
admet-10	182	15	consistent	consistent	ADJ
admet-10	182	16	with	with	ADP
admet-10	182	17	the	the	DET
admet-10	182	18	fact	fact	NOUN
admet-10	182	19	that	that	SCONJ
admet-10	182	20	toxicity	toxicity	NOUN
admet-10	182	21	may	may	AUX
admet-10	182	22	not	not	PART
admet-10	182	23	be	be	AUX
admet-10	182	24	a	a	DET
admet-10	182	25	critical	critical	ADJ
admet-10	182	26	issue	issue	NOUN
admet-10	182	27	in	in	ADP
admet-10	182	28	molecular	molecular	ADJ
admet-10	182	29	targeted	target	VERB
admet-10	182	30	compounds	compound	NOUN
admet-10	182	31	,	,	PUNCT
admet-10	182	32	as	as	ADP
admet-10	182	33	compared	compare	VERB
admet-10	182	34	with	with	ADP
admet-10	182	35	cytotoxic	cytotoxic	ADJ
admet-10	182	36	anticancer	anticancer	NOUN
admet-10	182	37	compounds	compound	NOUN
admet-10	182	38	.	.	PUNCT
admet-10	183	1	tam	tam	PROPN
admet-10	183	2	admet	admet	PROPN
admet-10	183	3	&	&	CCONJ
admet-10	183	4	dmpk	dmpk	PROPN
admet-10	183	5	1(4	1(4	NUM
admet-10	183	6	)	)	PUNCT
admet-10	183	7	(	(	PUNCT
admet-10	183	8	2013	2013	NUM
admet-10	183	9	)	)	PUNCT
admet-10	183	10	63	63	NUM
admet-10	183	11	-	-	SYM
admet-10	183	12	75	75	NUM
admet-10	183	13	72	72	NUM
admet-10	183	14	figure	figure	NOUN
admet-10	183	15	1	1	NUM
admet-10	183	16	.	.	PUNCT
admet-10	184	1	the	the	DET
admet-10	184	2	preclinical	preclinical	ADJ
admet-10	184	3	models	model	NOUN
admet-10	184	4	and	and	CCONJ
admet-10	184	5	toxicological	toxicological	ADJ
admet-10	184	6	parameters	parameter	NOUN
admet-10	184	7	used	use	VERB
admet-10	184	8	to	to	PART
admet-10	184	9	derive	derive	VERB
admet-10	184	10	the	the	DET
admet-10	184	11	starting	starting	NOUN
admet-10	184	12	dose	dose	NOUN
admet-10	184	13	of	of	ADP
admet-10	184	14	the	the	DET
admet-10	184	15	57	57	NUM
admet-10	184	16	phase	phase	NOUN
admet-10	184	17	1	1	NUM
admet-10	184	18	cancer	cancer	NOUN
admet-10	184	19	clinical	clinical	ADJ
admet-10	184	20	trials	trial	NOUN
admet-10	184	21	of	of	ADP
admet-10	184	22	molecular	molecular	ADJ
admet-10	184	23	targeted	target	VERB
admet-10	184	24	compounds	compound	NOUN
admet-10	184	25	(	(	PUNCT
admet-10	184	26	adapted	adapt	VERB
admet-10	184	27	from	from	ADP
admet-10	184	28	reference	reference	NOUN
admet-10	184	29	32	32	NUM
admet-10	184	30	)	)	PUNCT
admet-10	184	31	.	.	PUNCT
admet-10	185	1	mtd	mtd	PROPN
admet-10	185	2	,	,	PUNCT
admet-10	185	3	maximum	maximum	ADJ
admet-10	185	4	-	-	PUNCT
admet-10	185	5	tolerated	tolerate	VERB
admet-10	185	6	dose	dose	NOUN
admet-10	185	7	;	;	PUNCT
admet-10	185	8	ld10	ld10	PROPN
admet-10	185	9	,	,	PUNCT
admet-10	185	10	lethal	lethal	ADJ
admet-10	185	11	dose	dose	NOUN
admet-10	185	12	for	for	ADP
admet-10	185	13	10	10	NUM
admet-10	185	14	%	%	NOUN
admet-10	185	15	of	of	ADP
admet-10	185	16	animals	animal	NOUN
admet-10	185	17	;	;	PUNCT
admet-10	185	18	tdl	tdl	PROPN
admet-10	185	19	,	,	PUNCT
admet-10	185	20	toxic	toxic	ADJ
admet-10	185	21	dose	dose	NOUN
admet-10	185	22	low	low	ADJ
admet-10	185	23	;	;	PUNCT
admet-10	185	24	noael	noael	NUM
admet-10	185	25	,	,	PUNCT
admet-10	185	26	no	no	DET
admet-10	185	27	observed	observed	ADJ
admet-10	185	28	adverse	adverse	ADJ
admet-10	185	29	event	event	NOUN
admet-10	185	30	level	level	NOUN
admet-10	185	31	;	;	PUNCT
admet-10	185	32	std10	std10	ADV
admet-10	185	33	,	,	PUNCT
admet-10	185	34	severely	severely	ADV
admet-10	185	35	toxic	toxic	ADJ
admet-10	185	36	dose	dose	VERB
admet-10	185	37	for	for	ADP
admet-10	185	38	10	10	NUM
admet-10	185	39	%	%	NOUN
admet-10	185	40	of	of	ADP
admet-10	185	41	animals	animal	NOUN
admet-10	185	42	;	;	PUNCT
admet-10	185	43	med	me	VERB
admet-10	185	44	,	,	PUNCT
admet-10	185	45	minimum	minimum	ADJ
admet-10	185	46	effective	effective	ADJ
admet-10	185	47	dose	dose	NOUN
admet-10	185	48	.	.	PUNCT
admet-10	186	1	6.3	6.3	NUM
admet-10	186	2	.	.	PUNCT
admet-10	186	3	immune	immune	ADJ
admet-10	186	4	modulators	modulator	NOUN
admet-10	186	5	and	and	CCONJ
admet-10	186	6	monoclonal	monoclonal	NOUN
admet-10	186	7	antibodies	antibody	NOUN
admet-10	186	8	for	for	ADP
admet-10	186	9	these	these	DET
admet-10	186	10	kinds	kind	NOUN
admet-10	186	11	of	of	ADP
admet-10	186	12	compounds	compound	NOUN
admet-10	186	13	,	,	PUNCT
admet-10	186	14	it	it	PRON
admet-10	186	15	has	have	AUX
admet-10	186	16	been	be	AUX
admet-10	186	17	suggested	suggest	VERB
admet-10	186	18	that	that	SCONJ
admet-10	186	19	the	the	DET
admet-10	186	20	selection	selection	NOUN
admet-10	186	21	of	of	ADP
admet-10	186	22	starting	start	VERB
admet-10	186	23	dose	dose	NOUN
admet-10	186	24	may	may	AUX
admet-10	186	25	be	be	AUX
admet-10	186	26	supported	support	VERB
admet-10	186	27	by	by	ADP
admet-10	186	28	the	the	DET
admet-10	186	29	mabel	mabel	PROPN
admet-10	186	30	approach	approach	NOUN
admet-10	186	31	,	,	PUNCT
admet-10	186	32	as	as	SCONJ
admet-10	186	33	discussed	discuss	VERB
admet-10	186	34	in	in	ADP
admet-10	186	35	section	section	NOUN
admet-10	186	36	5	5	NUM
admet-10	187	1	[	[	X
admet-10	187	2	27	27	NUM
admet-10	187	3	]	]	PUNCT
admet-10	187	4	.	.	PUNCT
admet-10	188	1	6.4	6.4	NUM
admet-10	188	2	.	.	PUNCT
admet-10	188	3	combination	combination	NOUN
admet-10	188	4	therapy	therapy	NOUN
admet-10	188	5	studies	study	NOUN
admet-10	188	6	cytotoxic	cytotoxic	ADJ
admet-10	188	7	compounds	compound	NOUN
admet-10	188	8	have	have	AUX
admet-10	188	9	been	be	AUX
admet-10	188	10	used	use	VERB
admet-10	188	11	in	in	ADP
admet-10	188	12	combination	combination	NOUN
admet-10	188	13	to	to	PART
admet-10	188	14	increase	increase	VERB
admet-10	188	15	the	the	DET
admet-10	188	16	anti	anti	ADJ
admet-10	188	17	-	-	ADJ
admet-10	188	18	tumour	tumour	ADJ
admet-10	188	19	activity	activity	NOUN
admet-10	188	20	at	at	ADP
admet-10	188	21	acceptable	acceptable	ADJ
admet-10	188	22	levels	level	NOUN
admet-10	188	23	of	of	ADP
admet-10	188	24	toxicity	toxicity	NOUN
admet-10	188	25	.	.	PUNCT
admet-10	189	1	this	this	PRON
admet-10	189	2	may	may	AUX
admet-10	189	3	be	be	AUX
admet-10	189	4	accomplished	accomplish	VERB
admet-10	189	5	by	by	ADP
admet-10	189	6	combining	combine	VERB
admet-10	189	7	compounds	compound	NOUN
admet-10	189	8	with	with	ADP
admet-10	189	9	at	at	ADV
admet-10	189	10	least	least	ADJ
admet-10	189	11	partly	partly	ADV
admet-10	189	12	non	non	ADJ
admet-10	189	13	-	-	ADJ
admet-10	189	14	overlapping	overlapping	ADJ
admet-10	189	15	toxicity	toxicity	NOUN
admet-10	189	16	,	,	PUNCT
admet-10	189	17	activity	activity	NOUN
admet-10	189	18	or	or	CCONJ
admet-10	189	19	resistance	resistance	NOUN
admet-10	189	20	.	.	PUNCT
admet-10	190	1	however	however	ADV
admet-10	190	2	,	,	PUNCT
admet-10	190	3	it	it	PRON
admet-10	190	4	may	may	AUX
admet-10	190	5	be	be	AUX
admet-10	190	6	difficult	difficult	ADJ
admet-10	190	7	to	to	PART
admet-10	190	8	predict	predict	VERB
admet-10	190	9	whether	whether	SCONJ
admet-10	190	10	this	this	DET
admet-10	190	11	kind	kind	NOUN
admet-10	190	12	of	of	ADP
admet-10	190	13	combination	combination	NOUN
admet-10	190	14	therapy	therapy	NOUN
admet-10	190	15	would	would	AUX
admet-10	190	16	lead	lead	VERB
admet-10	190	17	to	to	ADP
admet-10	190	18	a	a	DET
admet-10	190	19	better	well	ADJ
admet-10	190	20	treatment	treatment	NOUN
admet-10	190	21	outcome	outcome	NOUN
admet-10	190	22	than	than	ADP
admet-10	190	23	the	the	DET
admet-10	190	24	individual	individual	ADJ
admet-10	190	25	agents	agent	NOUN
admet-10	190	26	that	that	PRON
admet-10	190	27	are	be	AUX
admet-10	190	28	consecutively	consecutively	ADV
admet-10	190	29	used	use	VERB
admet-10	190	30	in	in	ADP
admet-10	190	31	isolation	isolation	NOUN
admet-10	190	32	.	.	PUNCT
admet-10	191	1	in	in	ADP
admet-10	191	2	combining	combine	VERB
admet-10	191	3	two	two	NUM
admet-10	191	4	conventional	conventional	ADJ
admet-10	191	5	cytotoxic	cytotoxic	ADJ
admet-10	191	6	compounds	compound	NOUN
admet-10	191	7	,	,	PUNCT
admet-10	191	8	it	it	PRON
admet-10	191	9	may	may	AUX
admet-10	191	10	be	be	AUX
admet-10	191	11	possible	possible	ADJ
admet-10	191	12	to	to	PART
admet-10	191	13	predict	predict	VERB
admet-10	191	14	the	the	DET
admet-10	191	15	toxicity	toxicity	NOUN
admet-10	191	16	based	base	VERB
admet-10	191	17	on	on	ADP
admet-10	191	18	the	the	DET
admet-10	191	19	toxicities	toxicity	NOUN
admet-10	191	20	of	of	ADP
admet-10	191	21	individual	individual	ADJ
admet-10	191	22	components	component	NOUN
admet-10	191	23	.	.	PUNCT
admet-10	192	1	assuming	assume	VERB
admet-10	192	2	that	that	SCONJ
admet-10	192	3	the	the	DET
admet-10	192	4	pk	pk	NOUN
admet-10	192	5	interactions	interaction	NOUN
admet-10	192	6	of	of	ADP
admet-10	192	7	the	the	DET
admet-10	192	8	two	two	NUM
admet-10	192	9	compounds	compound	NOUN
admet-10	192	10	admet	admet	PROPN
admet-10	192	11	&	&	CCONJ
admet-10	192	12	dmpk	dmpk	PROPN
admet-10	192	13	1(4	1(4	NUM
admet-10	192	14	)	)	PUNCT
admet-10	192	15	(	(	PUNCT
admet-10	192	16	2013	2013	NUM
admet-10	192	17	)	)	PUNCT
admet-10	192	18	63	63	NUM
admet-10	192	19	-	-	SYM
admet-10	192	20	75	75	NUM
admet-10	192	21	estimating	estimate	VERB
admet-10	192	22	first	first	ADV
admet-10	192	23	in	in	ADP
admet-10	192	24	human	human	PROPN
admet-10	192	25	dose	dose	NOUN
admet-10	192	26	doi	doi	PROPN
admet-10	192	27	:	:	PUNCT
admet-10	192	28	10.5599	10.5599	NUM
admet-10	192	29	/	/	SYM
admet-10	192	30	admet.1.4.10	admet.1.4.10	ADJ
admet-10	192	31	73	73	NUM
admet-10	192	32	are	be	AUX
admet-10	192	33	negligible	negligible	ADJ
admet-10	192	34	,	,	PUNCT
admet-10	192	35	the	the	DET
admet-10	192	36	starting	starting	NOUN
admet-10	192	37	dose	dose	NOUN
admet-10	192	38	could	could	AUX
admet-10	192	39	be	be	AUX
admet-10	192	40	about	about	ADV
admet-10	192	41	one	one	NUM
admet-10	192	42	half	half	NOUN
admet-10	192	43	of	of	ADP
admet-10	192	44	the	the	DET
admet-10	192	45	recommended	recommend	VERB
admet-10	192	46	mono	mono	NOUN
admet-10	192	47	-	-	PUNCT
admet-10	192	48	therapy	therapy	NOUN
admet-10	192	49	dose	dose	NOUN
admet-10	192	50	for	for	ADP
admet-10	192	51	each	each	DET
admet-10	192	52	compound	compound	NOUN
admet-10	192	53	[	[	X
admet-10	192	54	27	27	NUM
admet-10	192	55	]	]	PUNCT
admet-10	192	56	.	.	PUNCT
admet-10	193	1	if	if	SCONJ
admet-10	193	2	the	the	DET
admet-10	193	3	hypothesised	hypothesised	ADJ
admet-10	193	4	interaction	interaction	NOUN
admet-10	193	5	would	would	AUX
admet-10	193	6	lead	lead	VERB
admet-10	193	7	to	to	ADP
admet-10	193	8	an	an	DET
admet-10	193	9	anticipated	anticipate	VERB
admet-10	193	10	increased	increase	VERB
admet-10	193	11	drug	drug	NOUN
admet-10	193	12	exposure	exposure	NOUN
admet-10	193	13	,	,	PUNCT
admet-10	193	14	the	the	DET
admet-10	193	15	first	first	ADJ
admet-10	193	16	dose	dose	NOUN
admet-10	193	17	-	-	PUNCT
admet-10	193	18	level	level	NOUN
admet-10	193	19	should	should	AUX
admet-10	193	20	be	be	AUX
admet-10	193	21	cautiously	cautiously	ADV
admet-10	193	22	low	low	ADJ
admet-10	193	23	.	.	PUNCT
admet-10	194	1	alternatively	alternatively	ADV
admet-10	194	2	,	,	PUNCT
admet-10	194	3	it	it	PRON
admet-10	194	4	may	may	AUX
admet-10	194	5	be	be	AUX
admet-10	194	6	reasonable	reasonable	ADJ
admet-10	194	7	to	to	PART
admet-10	194	8	start	start	VERB
admet-10	194	9	at	at	ADP
admet-10	194	10	the	the	DET
admet-10	194	11	recommended	recommend	VERB
admet-10	194	12	dose	dose	NOUN
admet-10	194	13	for	for	ADP
admet-10	194	14	one	one	NUM
admet-10	194	15	compound	compound	NOUN
admet-10	194	16	and	and	CCONJ
admet-10	194	17	a	a	DET
admet-10	194	18	reduced	reduce	VERB
admet-10	194	19	dose	dose	NOUN
admet-10	194	20	(	(	PUNCT
admet-10	194	21	<	<	X
admet-10	194	22	50	50	NUM
admet-10	194	23	%	%	NOUN
admet-10	194	24	)	)	PUNCT
admet-10	194	25	of	of	ADP
admet-10	194	26	the	the	DET
admet-10	194	27	other	other	ADJ
admet-10	194	28	.	.	PUNCT
admet-10	195	1	in	in	ADP
admet-10	195	2	cases	case	NOUN
admet-10	195	3	where	where	SCONJ
admet-10	195	4	at	at	ADP
admet-10	195	5	least	least	ADJ
admet-10	195	6	of	of	ADP
admet-10	195	7	one	one	NUM
admet-10	195	8	the	the	DET
admet-10	195	9	two	two	NUM
admet-10	195	10	components	component	NOUN
admet-10	195	11	is	be	AUX
admet-10	195	12	a	a	DET
admet-10	195	13	non	non	ADJ
admet-10	195	14	-	-	ADJ
admet-10	195	15	cytotoxic	cytotoxic	ADJ
admet-10	195	16	compound	compound	NOUN
admet-10	195	17	,	,	PUNCT
admet-10	195	18	it	it	PRON
admet-10	195	19	is	be	AUX
admet-10	195	20	desirable	desirable	ADJ
admet-10	195	21	to	to	PART
admet-10	195	22	have	have	VERB
admet-10	195	23	compelling	compelling	ADJ
admet-10	195	24	preclinical	preclinical	ADJ
admet-10	195	25	rationale	rationale	NOUN
admet-10	195	26	to	to	PART
admet-10	195	27	support	support	VERB
admet-10	195	28	the	the	DET
admet-10	195	29	combination	combination	NOUN
admet-10	195	30	study	study	NOUN
admet-10	195	31	[	[	X
admet-10	195	32	33	33	NUM
admet-10	195	33	]	]	PUNCT
admet-10	195	34	.	.	PUNCT
admet-10	196	1	this	this	DET
admet-10	196	2	kind	kind	NOUN
admet-10	196	3	of	of	ADP
admet-10	196	4	combination	combination	NOUN
admet-10	196	5	phase	phase	NOUN
admet-10	196	6	1	1	NUM
admet-10	196	7	study	study	NOUN
admet-10	196	8	is	be	AUX
admet-10	196	9	very	very	ADV
admet-10	196	10	complex	complex	ADJ
admet-10	196	11	.	.	PUNCT
admet-10	197	1	the	the	DET
admet-10	197	2	methodology	methodology	NOUN
admet-10	197	3	for	for	ADP
admet-10	197	4	the	the	DET
admet-10	197	5	development	development	NOUN
admet-10	197	6	of	of	ADP
admet-10	197	7	innovative	innovative	ADJ
admet-10	197	8	cancer	cancer	NOUN
admet-10	197	9	therapies	therapy	NOUN
admet-10	197	10	(	(	PUNCT
admet-10	197	11	mdict	mdict	ADJ
admet-10	197	12	)	)	PUNCT
admet-10	197	13	task	task	NOUN
admet-10	197	14	force	force	NOUN
admet-10	197	15	has	have	AUX
admet-10	197	16	recently	recently	ADV
admet-10	197	17	published	publish	VERB
admet-10	197	18	a	a	DET
admet-10	197	19	paper	paper	NOUN
admet-10	197	20	concerning	concern	VERB
admet-10	197	21	recommendations	recommendation	NOUN
admet-10	197	22	on	on	ADP
admet-10	197	23	combination	combination	NOUN
admet-10	197	24	therapy	therapy	NOUN
admet-10	197	25	studies	study	NOUN
admet-10	197	26	[	[	X
admet-10	197	27	34	34	NUM
admet-10	197	28	]	]	PUNCT
admet-10	197	29	.	.	PUNCT
admet-10	198	1	with	with	ADP
admet-10	198	2	regard	regard	NOUN
admet-10	198	3	to	to	ADP
admet-10	198	4	the	the	DET
admet-10	198	5	schedule	schedule	NOUN
admet-10	198	6	and	and	CCONJ
admet-10	198	7	dose	dose	NOUN
admet-10	198	8	,	,	PUNCT
admet-10	198	9	the	the	DET
admet-10	198	10	paper	paper	NOUN
admet-10	198	11	simply	simply	ADV
admet-10	198	12	remarked	remark	VERB
admet-10	198	13	that	that	SCONJ
admet-10	198	14	they	they	PRON
admet-10	198	15	“	"	PUNCT
admet-10	198	16	should	should	AUX
admet-10	198	17	be	be	AUX
admet-10	198	18	formally	formally	ADV
admet-10	198	19	explored	explore	VERB
admet-10	198	20	for	for	ADP
admet-10	198	21	e.g.	e.g.	ADV
admet-10	198	22	with	with	ADP
admet-10	198	23	a	a	DET
admet-10	198	24	randomised	randomised	ADJ
admet-10	198	25	or	or	CCONJ
admet-10	198	26	adaptive	adaptive	ADJ
admet-10	198	27	design	design	NOUN
admet-10	198	28	”	"	PUNCT
admet-10	198	29	.	.	PUNCT
admet-10	199	1	as	as	ADV
admet-10	199	2	far	far	ADV
admet-10	199	3	as	as	SCONJ
admet-10	199	4	we	we	PRON
admet-10	199	5	are	be	AUX
admet-10	199	6	aware	aware	ADJ
admet-10	199	7	,	,	PUNCT
admet-10	199	8	little	little	ADJ
admet-10	199	9	,	,	PUNCT
admet-10	199	10	if	if	SCONJ
admet-10	199	11	any	any	PRON
admet-10	199	12	,	,	PUNCT
admet-10	199	13	information	information	NOUN
admet-10	199	14	is	be	AUX
admet-10	199	15	available	available	ADJ
admet-10	199	16	in	in	ADP
admet-10	199	17	open	open	ADJ
admet-10	199	18	literature	literature	NOUN
admet-10	199	19	describing	describe	VERB
admet-10	199	20	the	the	DET
admet-10	199	21	estimation	estimation	NOUN
admet-10	199	22	of	of	ADP
admet-10	199	23	starting	start	VERB
admet-10	199	24	dose	dose	NOUN
admet-10	199	25	and	and	CCONJ
admet-10	199	26	clinical	clinical	ADJ
admet-10	199	27	trial	trial	NOUN
admet-10	199	28	design	design	NOUN
admet-10	199	29	in	in	ADP
admet-10	199	30	this	this	DET
admet-10	199	31	kind	kind	NOUN
admet-10	199	32	of	of	ADP
admet-10	199	33	study	study	NOUN
admet-10	199	34	.	.	PUNCT
admet-10	200	1	given	give	VERB
admet-10	200	2	the	the	DET
admet-10	200	3	high	high	ADJ
admet-10	200	4	uncertainty	uncertainty	NOUN
admet-10	200	5	to	to	PART
admet-10	200	6	predict	predict	VERB
admet-10	200	7	the	the	DET
admet-10	200	8	add	add	VERB
admet-10	200	9	-	-	PUNCT
admet-10	200	10	on	on	ADP
admet-10	200	11	activity	activity	NOUN
admet-10	200	12	in	in	ADP
admet-10	200	13	non	non	ADJ
admet-10	200	14	-	-	ADJ
admet-10	200	15	clinical	clinical	ADJ
admet-10	200	16	models	model	NOUN
admet-10	200	17	,	,	PUNCT
admet-10	200	18	the	the	DET
admet-10	200	19	emea	emea	NOUN
admet-10	200	20	has	have	AUX
admet-10	200	21	recommended	recommend	VERB
admet-10	200	22	the	the	DET
admet-10	200	23	incorporation	incorporation	NOUN
admet-10	200	24	of	of	ADP
admet-10	200	25	randomised	randomised	ADJ
admet-10	200	26	phase	phase	NOUN
admet-10	200	27	2	2	NUM
admet-10	200	28	studies	study	NOUN
admet-10	200	29	to	to	PART
admet-10	200	30	compare	compare	VERB
admet-10	200	31	the	the	DET
admet-10	200	32	experimental	experimental	ADJ
admet-10	200	33	regimen	regiman	NOUN
admet-10	200	34	with	with	ADP
admet-10	200	35	the	the	DET
admet-10	200	36	chemotherapy	chemotherapy	NOUN
admet-10	200	37	-	-	ADJ
admet-10	200	38	alone	alone	ADJ
admet-10	200	39	regimen	regiman	NOUN
admet-10	201	1	[	[	X
admet-10	201	2	27	27	NUM
admet-10	201	3	]	]	PUNCT
admet-10	201	4	.	.	PUNCT
admet-10	202	1	7	7	X
admet-10	202	2	.	.	X
admet-10	202	3	conclusions	conclusion	NOUN
admet-10	202	4	estimation	estimation	NOUN
admet-10	202	5	of	of	ADP
admet-10	202	6	the	the	DET
admet-10	202	7	fih	fih	NOUN
admet-10	202	8	dose	dose	NOUN
admet-10	202	9	is	be	AUX
admet-10	202	10	one	one	NUM
admet-10	202	11	of	of	ADP
admet-10	202	12	the	the	DET
admet-10	202	13	important	important	ADJ
admet-10	202	14	steps	step	NOUN
admet-10	202	15	in	in	ADP
admet-10	202	16	phase	phase	NOUN
admet-10	202	17	1	1	NUM
admet-10	202	18	clinical	clinical	ADJ
admet-10	202	19	trials	trial	NOUN
admet-10	202	20	.	.	PUNCT
admet-10	203	1	the	the	DET
admet-10	203	2	initial	initial	ADJ
admet-10	203	3	human	human	ADJ
admet-10	203	4	dose	dose	NOUN
admet-10	203	5	has	have	VERB
admet-10	203	6	to	to	PART
admet-10	203	7	be	be	AUX
admet-10	203	8	low	low	ADJ
admet-10	203	9	enough	enough	ADV
admet-10	203	10	to	to	PART
admet-10	203	11	ensure	ensure	VERB
admet-10	203	12	the	the	DET
admet-10	203	13	safety	safety	NOUN
admet-10	203	14	of	of	ADP
admet-10	203	15	the	the	DET
admet-10	203	16	human	human	ADJ
admet-10	203	17	participants	participant	NOUN
admet-10	203	18	,	,	PUNCT
admet-10	203	19	but	but	CCONJ
admet-10	203	20	not	not	PART
admet-10	203	21	so	so	ADV
admet-10	203	22	conservative	conservative	ADJ
admet-10	203	23	that	that	SCONJ
admet-10	203	24	excessively	excessively	ADV
admet-10	203	25	costly	costly	ADJ
admet-10	203	26	and	and	CCONJ
admet-10	203	27	time	time	NOUN
admet-10	203	28	-	-	PUNCT
admet-10	203	29	consuming	consume	VERB
admet-10	203	30	dose	dose	NOUN
admet-10	203	31	escalations	escalation	NOUN
admet-10	203	32	are	be	AUX
admet-10	203	33	needed	need	VERB
admet-10	203	34	.	.	PUNCT
admet-10	204	1	the	the	DET
admet-10	204	2	noeal	noeal	ADJ
admet-10	204	3	approach	approach	NOUN
admet-10	204	4	endorsed	endorse	VERB
admet-10	204	5	by	by	ADP
admet-10	204	6	the	the	DET
admet-10	204	7	fda	fda	PROPN
admet-10	204	8	[	[	X
admet-10	204	9	3	3	X
admet-10	204	10	]	]	PUNCT
admet-10	204	11	is	be	AUX
admet-10	204	12	a	a	DET
admet-10	204	13	commonly	commonly	ADV
admet-10	204	14	used	use	VERB
admet-10	204	15	method	method	NOUN
admet-10	204	16	to	to	PART
admet-10	204	17	perform	perform	VERB
admet-10	204	18	the	the	DET
admet-10	204	19	initial	initial	ADJ
admet-10	204	20	dose	dose	NOUN
admet-10	204	21	prediction	prediction	NOUN
admet-10	204	22	.	.	PUNCT
admet-10	205	1	this	this	PRON
admet-10	205	2	is	be	AUX
admet-10	205	3	based	base	VERB
admet-10	205	4	on	on	ADP
admet-10	205	5	the	the	DET
admet-10	205	6	data	datum	NOUN
admet-10	205	7	obtained	obtain	VERB
admet-10	205	8	from	from	ADP
admet-10	205	9	preclinical	preclinical	ADJ
admet-10	205	10	toxicology	toxicology	NOUN
admet-10	205	11	studies	study	NOUN
admet-10	205	12	.	.	PUNCT
admet-10	206	1	following	follow	VERB
admet-10	206	2	the	the	DET
admet-10	206	3	tragic	tragic	ADJ
admet-10	206	4	incident	incident	NOUN
admet-10	206	5	of	of	ADP
admet-10	206	6	the	the	DET
admet-10	206	7	tgn1412	tgn1412	ADJ
admet-10	206	8	phase	phase	NOUN
admet-10	206	9	1	1	NUM
admet-10	206	10	trial	trial	NOUN
admet-10	206	11	,	,	PUNCT
admet-10	206	12	it	it	PRON
admet-10	206	13	has	have	AUX
admet-10	206	14	been	be	AUX
admet-10	206	15	recognised	recognise	VERB
admet-10	206	16	that	that	SCONJ
admet-10	206	17	the	the	DET
admet-10	206	18	noeal	noeal	ADJ
admet-10	206	19	approach	approach	NOUN
admet-10	206	20	might	might	AUX
admet-10	206	21	not	not	PART
admet-10	206	22	be	be	AUX
admet-10	206	23	sufficient	sufficient	ADJ
admet-10	206	24	to	to	PART
admet-10	206	25	provide	provide	VERB
admet-10	206	26	a	a	DET
admet-10	206	27	safe	safe	ADJ
admet-10	206	28	initial	initial	ADJ
admet-10	206	29	dose	dose	NOUN
admet-10	206	30	estimate	estimate	NOUN
admet-10	206	31	,	,	PUNCT
admet-10	206	32	especially	especially	ADV
admet-10	206	33	for	for	ADP
admet-10	206	34	high	high	ADJ
admet-10	206	35	-	-	PUNCT
admet-10	206	36	risk	risk	NOUN
admet-10	206	37	investigative	investigative	ADJ
admet-10	206	38	medicinal	medicinal	ADJ
admet-10	206	39	products	product	NOUN
admet-10	206	40	that	that	PRON
admet-10	206	41	the	the	DET
admet-10	206	42	mechanisms	mechanism	NOUN
admet-10	206	43	of	of	ADP
admet-10	206	44	the	the	DET
admet-10	206	45	pharmacological	pharmacological	ADJ
admet-10	206	46	actions	action	NOUN
admet-10	206	47	in	in	ADP
admet-10	206	48	human	human	NOUN
admet-10	206	49	are	be	AUX
admet-10	206	50	not	not	PART
admet-10	206	51	fully	fully	ADV
admet-10	206	52	understood	understand	VERB
admet-10	206	53	.	.	PUNCT
admet-10	207	1	since	since	SCONJ
admet-10	207	2	then	then	ADV
admet-10	207	3	,	,	PUNCT
admet-10	207	4	the	the	DET
admet-10	207	5	emea	emea	PROPN
admet-10	207	6	has	have	AUX
admet-10	207	7	endorsed	endorse	VERB
admet-10	207	8	the	the	DET
admet-10	207	9	mabel	mabel	PROPN
admet-10	207	10	approaches	approach	VERB
admet-10	207	11	[	[	X
admet-10	207	12	5	5	NUM
admet-10	207	13	]	]	PUNCT
admet-10	207	14	for	for	ADP
admet-10	207	15	estimating	estimate	VERB
admet-10	207	16	the	the	DET
admet-10	207	17	fih	fih	NOUN
admet-10	207	18	dose	dose	NOUN
admet-10	207	19	of	of	ADP
admet-10	207	20	high	high	ADJ
admet-10	207	21	-	-	PUNCT
admet-10	207	22	risk	risk	NOUN
admet-10	207	23	investigative	investigative	ADJ
admet-10	207	24	medicinal	medicinal	ADJ
admet-10	207	25	products	product	NOUN
admet-10	207	26	.	.	PUNCT
admet-10	208	1	this	this	DET
admet-10	208	2	comprehensive	comprehensive	ADJ
admet-10	208	3	approach	approach	NOUN
admet-10	208	4	made	make	VERB
admet-10	208	5	use	use	NOUN
admet-10	208	6	of	of	ADP
admet-10	208	7	all	all	DET
admet-10	208	8	preclinical	preclinical	ADJ
admet-10	208	9	in	in	ADP
admet-10	208	10	vitro	vitro	X
admet-10	208	11	and	and	CCONJ
admet-10	208	12	in	in	ADP
admet-10	208	13	vivo	vivo	ADJ
admet-10	208	14	information	information	NOUN
admet-10	208	15	available	available	ADJ
admet-10	208	16	from	from	ADP
admet-10	208	17	pk	pk	PROPN
admet-10	208	18	/	/	SYM
admet-10	208	19	pd	pd	NOUN
admet-10	208	20	,	,	PUNCT
admet-10	208	21	which	which	PRON
admet-10	208	22	appears	appear	VERB
admet-10	208	23	to	to	PART
admet-10	208	24	provide	provide	VERB
admet-10	208	25	a	a	DET
admet-10	208	26	more	more	ADV
admet-10	208	27	conservative	conservative	ADJ
admet-10	208	28	estimate	estimate	NOUN
admet-10	208	29	of	of	ADP
admet-10	208	30	the	the	DET
admet-10	208	31	initial	initial	NOUN
admet-10	208	32	dose	dose	NOUN
admet-10	208	33	on	on	ADP
admet-10	208	34	many	many	ADJ
admet-10	208	35	occasions	occasion	NOUN
admet-10	208	36	.	.	PUNCT
admet-10	209	1	this	this	PRON
admet-10	209	2	is	be	AUX
admet-10	209	3	particularly	particularly	ADV
admet-10	209	4	useful	useful	ADJ
admet-10	209	5	for	for	ADP
admet-10	209	6	biologics	biologic	NOUN
admet-10	209	7	and/or	and/or	CCONJ
admet-10	209	8	high	high	ADJ
admet-10	209	9	-	-	PUNCT
admet-10	209	10	risk	risk	NOUN
admet-10	209	11	investigative	investigative	ADJ
admet-10	209	12	medicinal	medicinal	ADJ
admet-10	209	13	products	product	NOUN
admet-10	209	14	where	where	SCONJ
admet-10	209	15	the	the	DET
admet-10	209	16	toxicity	toxicity	NOUN
admet-10	209	17	is	be	AUX
admet-10	209	18	closely	closely	ADV
admet-10	209	19	related	relate	VERB
admet-10	209	20	to	to	ADP
admet-10	209	21	the	the	DET
admet-10	209	22	exaggerated	exaggerated	ADJ
admet-10	209	23	“	"	PUNCT
admet-10	209	24	on	on	ADP
admet-10	209	25	-	-	PUNCT
admet-10	209	26	target	target	NOUN
admet-10	209	27	”	"	PUNCT
admet-10	209	28	pharmacology	pharmacology	NOUN
admet-10	209	29	.	.	PUNCT
admet-10	210	1	with	with	ADP
admet-10	210	2	regard	regard	NOUN
admet-10	210	3	to	to	ADP
admet-10	210	4	oncology	oncology	NOUN
admet-10	210	5	drugs	drug	NOUN
admet-10	210	6	,	,	PUNCT
admet-10	210	7	they	they	PRON
admet-10	210	8	are	be	AUX
admet-10	210	9	somewhat	somewhat	ADV
admet-10	210	10	different	different	ADJ
admet-10	210	11	from	from	ADP
admet-10	210	12	other	other	ADJ
admet-10	210	13	therapeutic	therapeutic	ADJ
admet-10	210	14	agents	agent	NOUN
admet-10	210	15	in	in	ADP
admet-10	210	16	terms	term	NOUN
admet-10	210	17	of	of	ADP
admet-10	210	18	clinical	clinical	ADJ
admet-10	210	19	evaluations	evaluation	NOUN
admet-10	210	20	and	and	CCONJ
admet-10	210	21	estimating	estimate	VERB
admet-10	210	22	the	the	DET
admet-10	210	23	fih	fih	NOUN
admet-10	210	24	dose	dose	NOUN
admet-10	210	25	.	.	PUNCT
admet-10	211	1	the	the	DET
admet-10	211	2	recently	recently	ADV
admet-10	211	3	published	publish	VERB
admet-10	211	4	emea	emea	PROPN
admet-10	211	5	guideline	guideline	NOUN
admet-10	211	6	[	[	X
admet-10	211	7	27	27	NUM
admet-10	211	8	]	]	PUNCT
admet-10	211	9	provided	provide	VERB
admet-10	211	10	upto	upto	ADJ
admet-10	211	11	-	-	PUNCT
admet-10	211	12	date	date	NOUN
admet-10	211	13	recommendations	recommendation	NOUN
admet-10	211	14	in	in	ADP
admet-10	211	15	the	the	DET
admet-10	211	16	clinical	clinical	ADJ
admet-10	211	17	study	study	NOUN
admet-10	211	18	of	of	ADP
admet-10	211	19	oncology	oncology	NOUN
admet-10	211	20	products	product	NOUN
admet-10	211	21	,	,	PUNCT
admet-10	211	22	which	which	PRON
admet-10	211	23	include	include	VERB
admet-10	211	24	:	:	PUNCT
admet-10	211	25	cytotoxics	cytotoxic	NOUN
admet-10	211	26	,	,	PUNCT
admet-10	211	27	noncytotoxics	noncytotoxic	NOUN
admet-10	211	28	,	,	PUNCT
admet-10	211	29	immune	immune	ADJ
admet-10	211	30	modulator	modulator	NOUN
admet-10	211	31	/	/	SYM
admet-10	211	32	monoclonal	monoclonal	NOUN
admet-10	211	33	antibody	antibody	NOUN
admet-10	211	34	and	and	CCONJ
admet-10	211	35	combination	combination	NOUN
admet-10	211	36	therapy	therapy	NOUN
admet-10	211	37	studies	study	NOUN
admet-10	211	38	.	.	PUNCT
admet-10	212	1	it	it	PRON
admet-10	212	2	is	be	AUX
admet-10	212	3	noted	note	VERB
admet-10	212	4	that	that	SCONJ
admet-10	212	5	the	the	DET
admet-10	212	6	fih	fih	NOUN
admet-10	212	7	dose	dose	NOUN
admet-10	212	8	estimation	estimation	NOUN
admet-10	212	9	for	for	ADP
admet-10	212	10	cytotoxics	cytotoxic	NOUN
admet-10	212	11	is	be	AUX
admet-10	212	12	usually	usually	ADV
admet-10	212	13	based	base	VERB
admet-10	212	14	on	on	ADP
admet-10	212	15	a	a	DET
admet-10	212	16	fraction	fraction	NOUN
admet-10	212	17	of	of	ADP
admet-10	212	18	the	the	DET
admet-10	212	19	lethal	lethal	ADJ
admet-10	212	20	dose	dose	NOUN
admet-10	212	21	obtained	obtain	VERB
admet-10	212	22	from	from	ADP
admet-10	212	23	preclinical	preclinical	ADJ
admet-10	212	24	toxicology	toxicology	NOUN
admet-10	212	25	studies	study	NOUN
admet-10	212	26	.	.	PUNCT
admet-10	213	1	for	for	ADP
admet-10	213	2	immune	immune	ADJ
admet-10	213	3	modulator	modulator	NOUN
admet-10	213	4	/	/	SYM
admet-10	213	5	monoclonal	monoclonal	NOUN
admet-10	213	6	antibodies	antibodie	VERB
admet-10	213	7	,	,	PUNCT
admet-10	213	8	the	the	DET
admet-10	213	9	mabel	mabel	PROPN
admet-10	213	10	approach	approach	NOUN
admet-10	213	11	is	be	AUX
admet-10	213	12	recommended	recommend	VERB
admet-10	213	13	.	.	PUNCT
admet-10	214	1	as	as	ADP
admet-10	214	2	for	for	ADP
admet-10	214	3	non	non	NOUN
admet-10	214	4	-	-	NOUN
admet-10	214	5	cytotoxics	cytotoxic	NOUN
admet-10	214	6	,	,	PUNCT
admet-10	214	7	the	the	DET
admet-10	214	8	selection	selection	NOUN
admet-10	214	9	of	of	ADP
admet-10	214	10	fih	fih	NOUN
admet-10	214	11	dose	dose	NOUN
admet-10	214	12	was	be	AUX
admet-10	214	13	based	base	VERB
admet-10	214	14	on	on	ADP
admet-10	214	15	diverse	diverse	ADJ
admet-10	214	16	practices	practice	NOUN
admet-10	214	17	.	.	PUNCT
admet-10	215	1	as	as	ADV
admet-10	215	2	far	far	ADV
admet-10	215	3	as	as	SCONJ
admet-10	215	4	we	we	PRON
admet-10	215	5	are	be	AUX
admet-10	215	6	aware	aware	ADJ
admet-10	215	7	,	,	PUNCT
admet-10	215	8	there	there	PRON
admet-10	215	9	is	be	VERB
admet-10	215	10	currently	currently	ADV
admet-10	215	11	no	no	DET
admet-10	215	12	established	establish	VERB
admet-10	215	13	protocol	protocol	NOUN
admet-10	215	14	or	or	CCONJ
admet-10	215	15	consensus	consensus	NOUN
admet-10	215	16	regarding	regard	VERB
admet-10	215	17	the	the	DET
admet-10	215	18	fih	fih	NOUN
admet-10	215	19	dose	dose	NOUN
admet-10	215	20	selection	selection	NOUN
admet-10	215	21	in	in	ADP
admet-10	215	22	combination	combination	NOUN
admet-10	215	23	therapy	therapy	NOUN
admet-10	215	24	studies	study	NOUN
admet-10	215	25	involving	involve	VERB
admet-10	215	26	molecular	molecular	ADJ
admet-10	215	27	targeted	target	VERB
admet-10	215	28	compound(s	compound(s	NOUN
admet-10	215	29	)	)	PUNCT
admet-10	215	30	.	.	PUNCT
admet-10	216	1	this	this	PRON
admet-10	216	2	reflects	reflect	VERB
admet-10	216	3	on	on	ADP
admet-10	216	4	the	the	DET
admet-10	216	5	complex	complex	ADJ
admet-10	216	6	nature	nature	NOUN
admet-10	216	7	of	of	ADP
admet-10	216	8	the	the	DET
admet-10	216	9	clinical	clinical	ADJ
admet-10	216	10	trial	trial	NOUN
admet-10	216	11	design	design	NOUN
admet-10	216	12	for	for	ADP
admet-10	216	13	this	this	DET
admet-10	216	14	kind	kind	NOUN
admet-10	216	15	of	of	ADP
admet-10	216	16	combination	combination	NOUN
admet-10	216	17	study	study	NOUN
admet-10	216	18	,	,	PUNCT
admet-10	216	19	which	which	PRON
admet-10	216	20	would	would	AUX
admet-10	216	21	have	have	VERB
admet-10	216	22	to	to	PART
admet-10	216	23	consider	consider	VERB
admet-10	216	24	a	a	DET
admet-10	216	25	“	"	PUNCT
admet-10	216	26	case	case	NOUN
admet-10	216	27	-	-	PUNCT
admet-10	216	28	by	by	ADP
admet-10	216	29	-	-	PUNCT
admet-10	216	30	case	case	NOUN
admet-10	216	31	”	"	PUNCT
admet-10	216	32	basis	basis	NOUN
admet-10	216	33	.	.	PUNCT
admet-10	217	1	references	reference	NOUN
admet-10	217	2	[	[	X
admet-10	217	3	1	1	X
admet-10	217	4	]	]	PUNCT
admet-10	217	5	s.	s.	PROPN
admet-10	217	6	derry	derry	PROPN
admet-10	217	7	,	,	PUNCT
admet-10	217	8	y.k	y.k	PROPN
admet-10	217	9	.	.	PROPN
admet-10	217	10	loke	loke	PROPN
admet-10	217	11	,	,	PUNCT
admet-10	217	12	j.k	j.k	PROPN
admet-10	217	13	aronson	aronson	PROPN
admet-10	217	14	,	,	PUNCT
admet-10	217	15	bmc	bmc	PROPN
admet-10	217	16	medical	medical	ADJ
admet-10	217	17	research	research	NOUN
admet-10	217	18	methodology	methodology	NOUN
admet-10	217	19	1	1	NUM
admet-10	217	20	(	(	PUNCT
admet-10	217	21	2001	2001	NUM
admet-10	217	22	)	)	PUNCT
admet-10	217	23	7	7	NUM
admet-10	217	24	.	.	PUNCT
admet-10	218	1	[	[	X
admet-10	218	2	2	2	NUM
admet-10	218	3	]	]	X
admet-10	218	4	d.l	d.l	PROPN
admet-10	218	5	.	.	PROPN
admet-10	218	6	streiner	streiner	PROPN
admet-10	218	7	,	,	PUNCT
admet-10	218	8	canadian	canadian	ADJ
admet-10	218	9	journal	journal	NOUN
admet-10	218	10	of	of	ADP
admet-10	218	11	neurological	neurological	ADJ
admet-10	218	12	sciences	science	NOUN
admet-10	218	13	34	34	NUM
admet-10	218	14	:	:	PUNCT
admet-10	218	15	s1	s1	NOUN
admet-10	218	16	(	(	PUNCT
admet-10	218	17	2007	2007	NUM
admet-10	218	18	)	)	PUNCT
admet-10	218	19	s37	s37	NOUN
admet-10	218	20	-	-	PUNCT
admet-10	218	21	s41	s41	NOUN
admet-10	218	22	.	.	PUNCT
admet-10	219	1	tam	tam	PROPN
admet-10	219	2	admet	admet	PROPN
admet-10	219	3	&	&	CCONJ
admet-10	219	4	dmpk	dmpk	PROPN
admet-10	219	5	1(4	1(4	NUM
admet-10	219	6	)	)	PUNCT
admet-10	219	7	(	(	PUNCT
admet-10	219	8	2013	2013	NUM
admet-10	219	9	)	)	PUNCT
admet-10	219	10	63	63	NUM
admet-10	219	11	-	-	SYM
admet-10	219	12	75	75	NUM
admet-10	219	13	74	74	NUM
admet-10	219	14	[	[	X
admet-10	219	15	3	3	X
admet-10	219	16	]	]	X
admet-10	219	17	fda	fda	PROPN
admet-10	219	18	guidance	guidance	NOUN
admet-10	219	19	for	for	ADP
admet-10	219	20	industry	industry	NOUN
admet-10	219	21	estimating	estimate	VERB
admet-10	219	22	the	the	DET
admet-10	219	23	maximum	maximum	ADJ
admet-10	219	24	safe	safe	ADJ
admet-10	219	25	dose	dose	NOUN
admet-10	219	26	in	in	ADP
admet-10	219	27	initial	initial	ADJ
admet-10	219	28	clinical	clinical	ADJ
admet-10	219	29	trials	trial	NOUN
admet-10	219	30	for	for	ADP
admet-10	219	31	therapeutics	therapeutic	NOUN
admet-10	219	32	in	in	ADP
admet-10	219	33	adult	adult	NOUN
admet-10	219	34	healthy	healthy	ADJ
admet-10	219	35	volunteers	volunteer	NOUN
admet-10	219	36	2005	2005	NUM
admet-10	219	37	,	,	PUNCT
admet-10	219	38	http://www.fda.gov/downloads/drugs/guidances/ucm078932.pdf	http://www.fda.gov/downloads/drugs/guidances/ucm078932.pdf	NOUN
admet-10	219	39	(	(	PUNCT
admet-10	219	40	accessed	access	VERB
admet-10	219	41	19	19	NUM
admet-10	219	42	june	june	NOUN
admet-10	219	43	,	,	PUNCT
admet-10	219	44	2013	2013	NUM
admet-10	219	45	)	)	PUNCT
admet-10	220	1	[	[	X
admet-10	220	2	4	4	X
admet-10	220	3	]	]	PUNCT
admet-10	220	4	expert	expert	ADJ
admet-10	220	5	scientific	scientific	ADJ
admet-10	220	6	group	group	NOUN
admet-10	220	7	on	on	ADP
admet-10	220	8	phase	phase	NOUN
admet-10	220	9	one	one	NUM
admet-10	220	10	clinical	clinical	ADJ
admet-10	220	11	trials	trial	NOUN
admet-10	220	12	final	final	ADJ
admet-10	220	13	report	report	NOUN
admet-10	220	14	2006	2006	NUM
admet-10	220	15	,	,	PUNCT
admet-10	220	16	http://www.tfscro.com/business/doc/final_report_of_the_expert_scientific_group_(esg).pdf	http://www.tfscro.com/business/doc/final_report_of_the_expert_scientific_group_(esg).pdf	PUNCT
admet-10	220	17	(	(	PUNCT
admet-10	220	18	accessed	access	VERB
admet-10	220	19	19	19	NUM
admet-10	220	20	june	june	NOUN
admet-10	220	21	,	,	PUNCT
admet-10	220	22	2013	2013	NUM
admet-10	220	23	)	)	PUNCT
admet-10	221	1	[	[	X
admet-10	221	2	5	5	X
admet-10	221	3	]	]	PUNCT
admet-10	221	4	emea	emea	NOUN
admet-10	221	5	guideline	guideline	NOUN
admet-10	221	6	on	on	ADP
admet-10	221	7	strategies	strategy	NOUN
admet-10	221	8	to	to	PART
admet-10	221	9	identify	identify	VERB
admet-10	221	10	and	and	CCONJ
admet-10	221	11	mitigate	mitigate	VERB
admet-10	221	12	risks	risk	NOUN
admet-10	221	13	for	for	ADP
admet-10	221	14	first	first	ADJ
admet-10	221	15	-	-	PUNCT
admet-10	221	16	in	in	ADP
admet-10	221	17	-	-	PUNCT
admet-10	221	18	human	human	ADJ
admet-10	221	19	clinical	clinical	ADJ
admet-10	221	20	trials	trial	NOUN
admet-10	221	21	with	with	ADP
admet-10	221	22	investigational	investigational	ADJ
admet-10	221	23	medicinal	medicinal	ADJ
admet-10	221	24	products	product	NOUN
admet-10	221	25	2007	2007	NUM
admet-10	221	26	,	,	PUNCT
admet-10	221	27	http://www.emea.europa.eu/docs/en_gb/document_library/scientific_guideline/2009/09/wc500	http://www.emea.europa.eu/docs/en_gb/document_library/scientific_guideline/2009/09/wc500	PROPN
admet-10	221	28	002988.pdf	002988.pdf	NOUN
admet-10	221	29	(	(	PUNCT
admet-10	221	30	accessed	access	VERB
admet-10	221	31	19	19	NUM
admet-10	221	32	june	june	NOUN
admet-10	221	33	,	,	PUNCT
admet-10	221	34	2013	2013	NUM
admet-10	221	35	)	)	PUNCT
admet-10	222	1	[	[	X
admet-10	222	2	6	6	NUM
admet-10	222	3	]	]	X
admet-10	222	4	j.j	j.j	PROPN
admet-10	222	5	.	.	PROPN
admet-10	222	6	degeorge	degeorge	PROPN
admet-10	222	7	,	,	PUNCT
admet-10	222	8	c.h	c.h	PROPN
admet-10	222	9	.	.	PROPN
admet-10	222	10	ahn	ahn	PROPN
admet-10	222	11	,	,	PUNCT
admet-10	222	12	p.a	p.a	PROPN
admet-10	222	13	.	.	PROPN
admet-10	222	14	andrews	andrews	PROPN
admet-10	222	15	,	,	PUNCT
admet-10	222	16	m.e	m.e	PROPN
admet-10	222	17	.	.	PROPN
admet-10	222	18	brower	brower	PROPN
admet-10	222	19	,	,	PUNCT
admet-10	222	20	d.w	d.w	PROPN
admet-10	222	21	.	.	PROPN
admet-10	222	22	giorgio	giorgio	PROPN
admet-10	222	23	,	,	PUNCT
admet-10	222	24	m.a	m.a	PROPN
admet-10	222	25	.	.	PROPN
admet-10	222	26	goheer	goheer	PROPN
admet-10	222	27	,	,	PUNCT
admet-10	222	28	d.y	d.y	PROPN
admet-10	222	29	.	.	PROPN
admet-10	222	30	lee	lee	PROPN
admet-10	222	31	-	-	PUNCT
admet-10	222	32	ham	ham	PROPN
admet-10	222	33	,	,	PUNCT
admet-10	222	34	w.d	w.d	PROPN
admet-10	222	35	.	.	PROPN
admet-10	222	36	mcguinn	mcguinn	PROPN
admet-10	222	37	,	,	PUNCT
admet-10	222	38	w.	w.	PROPN
admet-10	222	39	schmidt	schmidt	PROPN
admet-10	222	40	,	,	PUNCT
admet-10	222	41	c.j	c.j	PROPN
admet-10	222	42	.	.	PROPN
admet-10	222	43	sun	sun	PROPN
admet-10	222	44	,	,	PUNCT
admet-10	222	45	s.c	s.c	PROPN
admet-10	222	46	.	.	PROPN
admet-10	222	47	tripathi	tripathi	PROPN
admet-10	222	48	,	,	PUNCT
admet-10	222	49	cancer	cancer	NOUN
admet-10	222	50	chemotherapy	chemotherapy	NOUN
admet-10	222	51	and	and	CCONJ
admet-10	222	52	pharmacology	pharmacology	NOUN
admet-10	222	53	41	41	NUM
admet-10	222	54	(	(	PUNCT
admet-10	222	55	1998	1998	NUM
admet-10	222	56	)	)	PUNCT
admet-10	222	57	173	173	NUM
admet-10	222	58	-	-	SYM
admet-10	222	59	185	185	NUM
admet-10	222	60	.	.	PUNCT
admet-10	223	1	[	[	X
admet-10	223	2	7	7	X
admet-10	223	3	]	]	PUNCT
admet-10	223	4	ich	ich	NOUN
admet-10	223	5	guidelines	guideline	NOUN
admet-10	223	6	m3	m3	PROPN
admet-10	223	7	(	(	PUNCT
admet-10	223	8	r2	r2	PROPN
admet-10	223	9	)	)	PUNCT
admet-10	223	10	on	on	ADP
admet-10	223	11	non	non	ADJ
admet-10	223	12	-	-	ADJ
admet-10	223	13	clinical	clinical	ADJ
admet-10	223	14	safety	safety	NOUN
admet-10	223	15	studies	study	NOUN
admet-10	223	16	for	for	ADP
admet-10	223	17	clinical	clinical	ADJ
admet-10	223	18	trials	trial	NOUN
admet-10	223	19	2009	2009	NUM
admet-10	223	20	,	,	PUNCT
admet-10	223	21	http://www.emea.europa.eu/docs/en_gb/document_library/scientific_guideline/2009/09/wc500	http://www.emea.europa.eu/docs/en_gb/document_library/scientific_guideline/2009/09/wc500	PROPN
admet-10	223	22	002720.pdf	002720.pdf	PROPN
admet-10	223	23	(	(	PUNCT
admet-10	223	24	accessed	access	VERB
admet-10	223	25	20	20	NUM
admet-10	223	26	june	june	PROPN
admet-10	223	27	,	,	PUNCT
admet-10	223	28	2013	2013	NUM
admet-10	223	29	)	)	PUNCT
admet-10	224	1	[	[	X
admet-10	224	2	8	8	X
admet-10	224	3	]	]	X
admet-10	224	4	d.	d.	PROPN
admet-10	224	5	wang	wang	PROPN
admet-10	224	6	,	,	PUNCT
admet-10	224	7	a.	a.	PROPN
admet-10	224	8	bakhai	bakhai	PROPN
admet-10	224	9	,	,	PUNCT
admet-10	224	10	clinical	clinical	ADJ
admet-10	224	11	trialsa	trialsa	NOUN
admet-10	224	12	practical	practical	ADJ
admet-10	224	13	guide	guide	NOUN
admet-10	224	14	to	to	PART
admet-10	224	15	design	design	VERB
admet-10	224	16	,	,	PUNCT
admet-10	224	17	analysis	analysis	NOUN
admet-10	224	18	and	and	CCONJ
admet-10	224	19	reporting	reporting	NOUN
admet-10	224	20	,	,	PUNCT
admet-10	224	21	remedica	remedica	PROPN
admet-10	224	22	,	,	PUNCT
admet-10	224	23	london	london	PROPN
admet-10	224	24	,	,	PUNCT
admet-10	224	25	uk	uk	PROPN
admet-10	224	26	,	,	PUNCT
admet-10	224	27	2006	2006	NUM
admet-10	224	28	.	.	PUNCT
admet-10	225	1	[	[	X
admet-10	225	2	9	9	NUM
admet-10	225	3	]	]	PUNCT
admet-10	225	4	guidelines	guideline	NOUN
admet-10	225	5	for	for	ADP
admet-10	225	6	phase	phase	NOUN
admet-10	225	7	i	i	PRON
admet-10	225	8	clinical	clinical	ADJ
admet-10	225	9	trials	trial	NOUN
admet-10	225	10	2007	2007	NUM
admet-10	225	11	,	,	PUNCT
admet-10	225	12	http://www.abpi.org.uk/ourwork/library/guidelines/documents/phase1-trial-guidelines.pdf	http://www.abpi.org.uk/ourwork/library/guidelines/documents/phase1-trial-guidelines.pdf	NOUN
admet-10	225	13	(	(	PUNCT
admet-10	225	14	asccessed	asccesse	VERB
admet-10	225	15	12	12	NUM
admet-10	225	16	october	october	PROPN
admet-10	225	17	,	,	PUNCT
admet-10	225	18	2013	2013	NUM
admet-10	225	19	)	)	PUNCT
admet-10	226	1	[	[	X
admet-10	226	2	10	10	NUM
admet-10	226	3	]	]	X
admet-10	226	4	b.	b.	PROPN
admet-10	226	5	röhrig	röhrig	PROPN
admet-10	226	6	,	,	PUNCT
admet-10	226	7	j.b	j.b	PROPN
admet-10	226	8	.	.	PROPN
admet-10	226	9	du	du	PROPN
admet-10	226	10	prel	prel	PROPN
admet-10	226	11	,	,	PUNCT
admet-10	226	12	d.	d.	PROPN
admet-10	226	13	wachtlin	wachtlin	PROPN
admet-10	226	14	,	,	PUNCT
admet-10	226	15	r.	r.	PROPN
admet-10	226	16	kwiecien	kwiecien	PROPN
admet-10	226	17	,	,	PUNCT
admet-10	226	18	m.	m.	NOUN
admet-10	226	19	blettner	blettner	NOUN
admet-10	226	20	,	,	PUNCT
admet-10	226	21	deutsches	deutsche	NOUN
admet-10	226	22	ärzteblatt	ärzteblatt	PROPN
admet-10	226	23	international	international	ADJ
admet-10	226	24	107	107	NUM
admet-10	226	25	(	(	PUNCT
admet-10	226	26	2010	2010	NUM
admet-10	226	27	)	)	PUNCT
admet-10	226	28	552	552	NUM
admet-10	226	29	-	-	SYM
admet-10	226	30	556	556	NUM
admet-10	226	31	.	.	PUNCT
admet-10	227	1	[	[	X
admet-10	227	2	11	11	NUM
admet-10	227	3	]	]	X
admet-10	227	4	b.g	b.g	PROPN
admet-10	227	5	.	.	PROPN
admet-10	227	6	reigner	reigner	PROPN
admet-10	227	7	,	,	PUNCT
admet-10	227	8	k.s	k.s	PROPN
admet-10	227	9	.	.	PROPN
admet-10	227	10	blesch	blesch	PROPN
admet-10	227	11	,	,	PUNCT
admet-10	227	12	european	european	ADJ
admet-10	227	13	journal	journal	PROPN
admet-10	227	14	of	of	ADP
admet-10	227	15	clinical	clinical	ADJ
admet-10	227	16	pharmacology	pharmacology	NOUN
admet-10	227	17	57	57	NUM
admet-10	227	18	(	(	PUNCT
admet-10	227	19	2002	2002	NUM
admet-10	227	20	)	)	PUNCT
admet-10	227	21	835–845	835–845	NUM
admet-10	227	22	.	.	PUNCT
admet-10	228	1	[	[	X
admet-10	228	2	12	12	NUM
admet-10	228	3	]	]	PUNCT
admet-10	228	4	i.	i.	PROPN
admet-10	228	5	mahmood	mahmood	PROPN
admet-10	228	6	,	,	PUNCT
admet-10	228	7	m.d	m.d	PROPN
admet-10	228	8	.	.	PROPN
admet-10	228	9	green	green	PROPN
admet-10	228	10	,	,	PUNCT
admet-10	228	11	j.e	j.e	PROPN
admet-10	228	12	.	.	PROPN
admet-10	228	13	fisher	fisher	PROPN
admet-10	228	14	,	,	PUNCT
admet-10	228	15	journal	journal	NOUN
admet-10	228	16	of	of	ADP
admet-10	228	17	clinical	clinical	ADJ
admet-10	228	18	pharmacology	pharmacology	NOUN
admet-10	228	19	43	43	NUM
admet-10	228	20	(	(	PUNCT
admet-10	228	21	2003	2003	NUM
admet-10	228	22	)	)	PUNCT
admet-10	228	23	692	692	NUM
admet-10	228	24	-	-	NUM
admet-10	228	25	697	697	NUM
admet-10	228	26	.	.	PUNCT
admet-10	229	1	[	[	X
admet-10	229	2	13	13	NUM
admet-10	229	3	]	]	PUNCT
admet-10	229	4	t.	t.	PROPN
admet-10	229	5	hünig	hünig	PROPN
admet-10	229	6	,	,	PUNCT
admet-10	229	7	advances	advance	VERB
admet-10	229	8	in	in	ADP
admet-10	229	9	immunology	immunology	NOUN
admet-10	229	10	95	95	NUM
admet-10	229	11	(	(	PUNCT
admet-10	229	12	2007	2007	NUM
admet-10	229	13	)	)	PUNCT
admet-10	229	14	111–148	111–148	NUM
admet-10	229	15	.	.	PUNCT
admet-10	230	1	[	[	X
admet-10	230	2	14	14	NUM
admet-10	230	3	]	]	X
admet-10	230	4	m.j.h	m.j.h	ADJ
admet-10	230	5	.	.	PUNCT
admet-10	230	6	kenter	kenter	PROPN
admet-10	230	7	,	,	PUNCT
admet-10	230	8	a.f	a.f	PROPN
admet-10	230	9	.	.	PROPN
admet-10	230	10	cohen	cohen	PROPN
admet-10	230	11	,	,	PUNCT
admet-10	230	12	lancet	lancet	VERB
admet-10	230	13	368	368	NUM
admet-10	230	14	(	(	PUNCT
admet-10	230	15	2006	2006	NUM
admet-10	230	16	)	)	PUNCT
admet-10	230	17	1387–1391	1387–1391	NUM
admet-10	230	18	.	.	PUNCT
admet-10	231	1	[	[	X
admet-10	231	2	15	15	NUM
admet-10	231	3	]	]	X
admet-10	231	4	z.	z.	PROPN
admet-10	231	5	waibler	waibler	PROPN
admet-10	231	6	,	,	PUNCT
admet-10	231	7	l.y	l.y	PROPN
admet-10	231	8	.	.	PROPN
admet-10	231	9	sender	sender	PROPN
admet-10	231	10	,	,	PUNCT
admet-10	231	11	c.	c.	PROPN
admet-10	231	12	merten	merten	PROPN
admet-10	231	13	,	,	PUNCT
admet-10	231	14	r.	r.	PROPN
admet-10	231	15	hartig	hartig	PROPN
admet-10	231	16	,	,	PUNCT
admet-10	231	17	s.	s.	PROPN
admet-10	231	18	kliche	kliche	PROPN
admet-10	231	19	,	,	PUNCT
admet-10	231	20	m.	m.	NOUN
admet-10	231	21	gunzer	gunzer	NOUN
admet-10	231	22	,	,	PUNCT
admet-10	231	23	p.	p.	PROPN
admet-10	231	24	reichardt	reichardt	PROPN
admet-10	231	25	,	,	PUNCT
admet-10	231	26	u.	u.	PROPN
admet-10	231	27	kalinke	kalinke	PROPN
admet-10	231	28	,	,	PUNCT
admet-10	231	29	b.	b.	PROPN
admet-10	231	30	schraven	schraven	PROPN
admet-10	231	31	,	,	PUNCT
admet-10	231	32	plos	plos	PROPN
admet-10	231	33	one	one	NUM
admet-10	231	34	3(3	3(3	NUM
admet-10	231	35	)	)	PUNCT
admet-10	231	36	(	(	PUNCT
admet-10	231	37	2008	2008	NUM
admet-10	231	38	)	)	PUNCT
admet-10	232	1	e1708	e1708	NOUN
admet-10	233	1	[	[	X
admet-10	233	2	16	16	NUM
admet-10	233	3	]	]	X
admet-10	233	4	d.	d.	PROPN
admet-10	233	5	eastwood	eastwood	PROPN
admet-10	233	6	,	,	PUNCT
admet-10	233	7	l.	l.	PROPN
admet-10	233	8	findlay	findlay	PROPN
admet-10	233	9	,	,	PUNCT
admet-10	233	10	s.	s.	PROPN
admet-10	233	11	poole	poole	PROPN
admet-10	233	12	,	,	PUNCT
admet-10	233	13	c.	c.	PROPN
admet-10	233	14	bird	bird	PROPN
admet-10	233	15	,	,	PUNCT
admet-10	233	16	m.	m.	NOUN
admet-10	233	17	wadhwa	wadhwa	PROPN
admet-10	233	18	,	,	PUNCT
admet-10	233	19	m.	m.	NOUN
admet-10	233	20	moore	moore	PROPN
admet-10	233	21	,	,	PUNCT
admet-10	233	22	c.	c.	PROPN
admet-10	233	23	burns	burns	PROPN
admet-10	233	24	,	,	PUNCT
admet-10	233	25	r.	r.	PROPN
admet-10	233	26	thorpe	thorpe	PROPN
admet-10	233	27	,	,	PUNCT
admet-10	233	28	r.	r.	PROPN
admet-10	233	29	stebbings	stebbings	PROPN
admet-10	233	30	,	,	PUNCT
admet-10	233	31	british	british	ADJ
admet-10	233	32	journal	journal	PROPN
admet-10	233	33	of	of	ADP
admet-10	233	34	pharmacology	pharmacology	NOUN
admet-10	233	35	161	161	NUM
admet-10	233	36	(	(	PUNCT
admet-10	233	37	2010	2010	NUM
admet-10	233	38	)	)	PUNCT
admet-10	234	1	512–526	512–526	NUM
admet-10	234	2	.	.	PUNCT
admet-10	235	1	[	[	X
admet-10	235	2	17	17	NUM
admet-10	235	3	]	]	X
admet-10	235	4	b.	b.	PROPN
admet-10	235	5	schraven	schraven	PROPN
admet-10	235	6	,	,	PUNCT
admet-10	235	7	u.	u.	PROPN
admet-10	235	8	kalinke	kalinke	PROPN
admet-10	235	9	,	,	PUNCT
admet-10	235	10	immunity	immunity	NOUN
admet-10	235	11	28	28	NUM
admet-10	235	12	(	(	PUNCT
admet-10	235	13	2008	2008	NUM
admet-10	235	14	)	)	PUNCT
admet-10	235	15	591	591	NUM
admet-10	235	16	-	-	SYM
admet-10	235	17	595	595	NUM
admet-10	235	18	.	.	PUNCT
admet-10	236	1	[	[	X
admet-10	236	2	18	18	NUM
admet-10	236	3	]	]	X
admet-10	236	4	n.	n.	PROPN
admet-10	236	5	müller	müller	PROPN
admet-10	236	6	,	,	PUNCT
admet-10	236	7	j.	j.	PROPN
admet-10	236	8	van	van	PROPN
admet-10	236	9	den	den	PROPN
admet-10	236	10	brandt	brandt	PROPN
admet-10	236	11	,	,	PUNCT
admet-10	236	12	f.	f.	PROPN
admet-10	236	13	odoardi	odoardi	PROPN
admet-10	236	14	,	,	PUNCT
admet-10	236	15	d.	d.	PROPN
admet-10	236	16	tischner	tischner	PROPN
admet-10	236	17	,	,	PUNCT
admet-10	236	18	j.	j.	PROPN
admet-10	236	19	herath	herath	PROPN
admet-10	236	20	,	,	PUNCT
admet-10	236	21	a.	a.	NOUN
admet-10	236	22	flügel	flügel	PROPN
admet-10	236	23	,	,	PUNCT
admet-10	236	24	h.m	h.m	PROPN
admet-10	236	25	.	.	PROPN
admet-10	236	26	reichardt	reichardt	PROPN
admet-10	236	27	,	,	PUNCT
admet-10	236	28	journal	journal	NOUN
admet-10	236	29	of	of	ADP
admet-10	236	30	clinical	clinical	ADJ
admet-10	236	31	investigation	investigation	NOUN
admet-10	236	32	118	118	NUM
admet-10	236	33	(	(	PUNCT
admet-10	236	34	2008	2008	NUM
admet-10	236	35	)	)	PUNCT
admet-10	236	36	1405	1405	NUM
admet-10	236	37	-	-	SYM
admet-10	236	38	1416	1416	NUM
admet-10	236	39	.	.	PUNCT
admet-10	237	1	[	[	X
admet-10	237	2	19	19	NUM
admet-10	237	3	]	]	X
admet-10	237	4	c.j	c.j	PROPN
admet-10	237	5	.	.	PROPN
admet-10	237	6	horvath	horvath	PROPN
admet-10	237	7	,	,	PUNCT
admet-10	237	8	m.n	m.n	PROPN
admet-10	237	9	.	.	PROPN
admet-10	237	10	milton	milton	PROPN
admet-10	237	11	,	,	PUNCT
admet-10	237	12	toxicologic	toxicologic	NOUN
admet-10	237	13	pathology	pathology	NOUN
admet-10	237	14	37	37	NUM
admet-10	237	15	(	(	PUNCT
admet-10	237	16	2009	2009	NUM
admet-10	237	17	)	)	PUNCT
admet-10	237	18	372	372	NUM
admet-10	237	19	-	-	SYM
admet-10	237	20	383	383	NUM
admet-10	237	21	.	.	PUNCT
admet-10	238	1	[	[	X
admet-10	238	2	20	20	NUM
admet-10	238	3	]	]	PUNCT
admet-10	238	4	ich	ich	PROPN
admet-10	238	5	guidelines	guideline	NOUN
admet-10	238	6	s6	s6	PROPN
admet-10	238	7	(	(	PUNCT
admet-10	238	8	r1	r1	PROPN
admet-10	238	9	)	)	PUNCT
admet-10	238	10	preclinical	preclinical	ADJ
admet-10	238	11	safety	safety	NOUN
admet-10	238	12	evaluation	evaluation	NOUN
admet-10	238	13	of	of	ADP
admet-10	238	14	biotechnology	biotechnology	NOUN
admet-10	238	15	-	-	PUNCT
admet-10	238	16	derived	derive	VERB
admet-10	238	17	pharmaceuticals	pharmaceutical	NOUN
admet-10	238	18	2011	2011	NUM
admet-10	238	19	,	,	PUNCT
admet-10	238	20	http://www.emea.europa.eu/docs/en_gb/document_library/scientific_guideline/2009/09/wc500	http://www.emea.europa.eu/docs/en_gb/document_library/scientific_guideline/2009/09/wc500	PROPN
admet-10	238	21	002828.pdf	002828.pdf	NOUN
admet-10	238	22	(	(	PUNCT
admet-10	238	23	accessed	access	VERB
admet-10	238	24	24	24	NUM
admet-10	238	25	june	june	PROPN
admet-10	238	26	,	,	PUNCT
admet-10	238	27	2013	2013	NUM
admet-10	238	28	)	)	PUNCT
admet-10	238	29	.	.	PUNCT
admet-10	239	1	[	[	X
admet-10	239	2	21	21	NUM
admet-10	239	3	]	]	X
admet-10	239	4	p.j	p.j	PROPN
admet-10	239	5	.	.	PROPN
admet-10	239	6	lowe	lowe	PROPN
admet-10	239	7	,	,	PUNCT
admet-10	239	8	y.	y.	PROPN
admet-10	239	9	hijazi	hijazi	PROPN
admet-10	240	1	y	y	PROPN
admet-10	240	2	,	,	PUNCT
admet-10	240	3	o.	o.	PROPN
admet-10	240	4	luttringer	luttringer	PROPN
admet-10	240	5	,	,	PUNCT
admet-10	240	6	h.	h.	PROPN
admet-10	240	7	yin	yin	PROPN
admet-10	240	8	,	,	PUNCT
admet-10	240	9	r.	r.	PROPN
admet-10	240	10	sarangapani	sarangapani	PROPN
admet-10	240	11	,	,	PUNCT
admet-10	240	12	d.	d.	PROPN
admet-10	240	13	howard	howard	PROPN
admet-10	240	14	,	,	PUNCT
admet-10	240	15	xenobiotica	xenobiotica	PROPN
admet-10	240	16	37	37	NUM
admet-10	240	17	(	(	PUNCT
admet-10	240	18	2007	2007	NUM
admet-10	240	19	)	)	PUNCT
admet-10	240	20	13311354	13311354	NUM
admet-10	240	21	.	.	PUNCT
admet-10	241	1	[	[	X
admet-10	241	2	22	22	NUM
admet-10	241	3	]	]	X
admet-10	241	4	b.m	b.m	PROPN
admet-10	241	5	.	.	PROPN
admet-10	241	6	agoram	agoram	PROPN
admet-10	241	7	,	,	PUNCT
admet-10	241	8	british	british	ADJ
admet-10	241	9	journal	journal	PROPN
admet-10	241	10	of	of	ADP
admet-10	241	11	clinical	clinical	ADJ
admet-10	241	12	pharmacology	pharmacology	NOUN
admet-10	241	13	67	67	NUM
admet-10	241	14	(	(	PUNCT
admet-10	241	15	2008	2008	NUM
admet-10	241	16	)	)	PUNCT
admet-10	242	1	153–160	153–160	NUM
admet-10	242	2	.	.	PUNCT
admet-10	243	1	[	[	X
admet-10	243	2	23	23	NUM
admet-10	243	3	]	]	X
admet-10	243	4	p.y	p.y	PROPN
admet-10	243	5	.	.	PROPN
admet-10	243	6	muller	muller	PROPN
admet-10	243	7	,	,	PUNCT
admet-10	243	8	m.	m.	PROPN
admet-10	243	9	milton	milton	PROPN
admet-10	243	10	,	,	PUNCT
admet-10	243	11	p.	p.	PROPN
admet-10	243	12	lloyd	lloyd	PROPN
admet-10	243	13	,	,	PUNCT
admet-10	243	14	j.	j.	PROPN
admet-10	243	15	sims	sims	PROPN
admet-10	243	16	,	,	PUNCT
admet-10	243	17	f.r	f.r	PROPN
admet-10	243	18	.	.	PROPN
admet-10	243	19	brennan	brennan	PROPN
admet-10	243	20	,	,	PUNCT
admet-10	243	21	current	current	ADJ
admet-10	243	22	opinion	opinion	NOUN
admet-10	243	23	in	in	ADP
admet-10	243	24	biotechnology	biotechnology	NOUN
admet-10	243	25	20	20	NUM
admet-10	243	26	(	(	PUNCT
admet-10	243	27	2009	2009	NUM
admet-10	243	28	)	)	PUNCT
admet-10	243	29	722	722	NUM
admet-10	243	30	-	-	SYM
admet-10	243	31	729	729	NUM
admet-10	243	32	.	.	PUNCT
admet-10	244	1	[	[	X
admet-10	244	2	24	24	NUM
admet-10	244	3	]	]	X
admet-10	244	4	p.j	p.j	PROPN
admet-10	244	5	.	.	PROPN
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admet-10	244	7	,	,	PUNCT
admet-10	244	8	s.	s.	PROPN
admet-10	244	9	tannenbaum	tannenbaum	PROPN
admet-10	244	10	,	,	PUNCT
admet-10	244	11	k.	k.	PROPN
admet-10	244	12	wu	wu	PROPN
admet-10	244	13	,	,	PUNCT
admet-10	244	14	p.	p.	PROPN
admet-10	244	15	lloyd	lloyd	PROPN
admet-10	244	16	,	,	PUNCT
admet-10	244	17	j.	j.	PROPN
admet-10	244	18	sims	sims	PROPN
admet-10	244	19	,	,	PUNCT
admet-10	244	20	basic	basic	ADJ
admet-10	244	21	&	&	CCONJ
admet-10	244	22	clinical	clinical	ADJ
admet-10	244	23	pharmacology	pharmacology	NOUN
admet-10	244	24	&	&	CCONJ
admet-10	244	25	toxicology	toxicology	NOUN
admet-10	244	26	106	106	NUM
admet-10	244	27	(	(	PUNCT
admet-10	244	28	2009	2009	NUM
admet-10	244	29	)	)	PUNCT
admet-10	245	1	195–209	195–209	NUM
admet-10	245	2	.	.	PUNCT
admet-10	246	1	[	[	X
admet-10	246	2	25	25	NUM
admet-10	246	3	]	]	X
admet-10	246	4	j.p	j.p	PROPN
admet-10	246	5	.	.	PROPN
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admet-10	246	7	,	,	PUNCT
admet-10	246	8	the	the	DET
admet-10	246	9	aaps	aap	NOUN
admet-10	246	10	journal	journal	PROPN
admet-10	246	11	12	12	NUM
admet-10	246	12	(	(	PUNCT
admet-10	246	13	2010	2010	NUM
admet-10	246	14	)	)	PUNCT
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admet-10	246	16	-	-	SYM
admet-10	246	17	758	758	NUM
admet-10	246	18	.	.	PUNCT
admet-10	247	1	[	[	X
admet-10	247	2	26	26	NUM
admet-10	247	3	]	]	PUNCT
admet-10	247	4	j.	j.	PROPN
admet-10	247	5	yu	yu	PROPN
admet-10	247	6	,	,	PUNCT
admet-10	247	7	h.	h.	PROPN
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admet-10	247	9	,	,	PUNCT
admet-10	247	10	a.l	a.l	PROPN
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admet-10	247	13	,	,	PUNCT
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admet-10	247	17	,	,	PUNCT
admet-10	247	18	the	the	DET
admet-10	247	19	aaps	aap	NOUN
admet-10	247	20	journal	journal	PROPN
admet-10	247	21	13	13	NUM
admet-10	247	22	(	(	PUNCT
admet-10	247	23	2011	2011	NUM
admet-10	247	24	)	)	PUNCT
admet-10	247	25	160	160	NUM
admet-10	247	26	-	-	SYM
admet-10	247	27	178	178	NUM
admet-10	247	28	.	.	PUNCT
admet-10	248	1	http://www.fda.gov/downloads/drugs/guidances/ucm078932.pdf	http://www.fda.gov/downloads/drugs/guidances/ucm078932.pdf	PROPN
admet-10	248	2	http://www.tfscro.com/business/doc/final_report_of_the_expert_scientific_group_(esg).pdf	http://www.tfscro.com/business/doc/final_report_of_the_expert_scientific_group_(esg).pdf	PROPN
admet-10	248	3	http://www.emea.europa.eu/docs/en_gb/document_library/scientific_guideline/2009/09/wc500002988.pdf	http://www.emea.europa.eu/docs/en_gb/document_library/scientific_guideline/2009/09/wc500002988.pdf	PROPN
admet-10	248	4	http://www.emea.europa.eu/docs/en_gb/document_library/scientific_guideline/2009/09/wc500002988.pdf	http://www.emea.europa.eu/docs/en_gb/document_library/scientific_guideline/2009/09/wc500002988.pdf	PROPN
admet-10	248	5	http://www.emea.europa.eu/docs/en_gb/document_library/scientific_guideline/2009/09/wc500002720.pdf	http://www.emea.europa.eu/docs/en_gb/document_library/scientific_guideline/2009/09/wc500002720.pdf	PROPN
admet-10	248	6	http://www.emea.europa.eu/docs/en_gb/document_library/scientific_guideline/2009/09/wc500002720.pdf	http://www.emea.europa.eu/docs/en_gb/document_library/scientific_guideline/2009/09/wc500002720.pdf	PROPN
admet-10	248	7	http://www.abpi.org.uk/our-work/library/guidelines/documents/phase1-trial-guidelines.pdf	http://www.abpi.org.uk/our-work/library/guidelines/documents/phase1-trial-guidelines.pdf	NOUN
admet-10	248	8	http://www.abpi.org.uk/our-work/library/guidelines/documents/phase1-trial-guidelines.pdf	http://www.abpi.org.uk/our-work/library/guidelines/documents/phase1-trial-guidelines.pdf	PROPN
admet-10	248	9	http://www.emea.europa.eu/docs/en_gb/document_library/scientific_guideline/2009/09/wc500002828.pdf	http://www.emea.europa.eu/docs/en_gb/document_library/scientific_guideline/2009/09/wc500002828.pdf	PROPN
admet-10	248	10	http://www.emea.europa.eu/docs/en_gb/document_library/scientific_guideline/2009/09/wc500002828.pdf	http://www.emea.europa.eu/docs/en_gb/document_library/scientific_guideline/2009/09/wc500002828.pdf	PROPN
admet-10	248	11	admet	admet	PROPN
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admet-10	248	13	dmpk	dmpk	PROPN
admet-10	248	14	1(4	1(4	NUM
admet-10	248	15	)	)	PUNCT
admet-10	248	16	(	(	PUNCT
admet-10	248	17	2013	2013	NUM
admet-10	248	18	)	)	PUNCT
admet-10	248	19	63	63	NUM
admet-10	248	20	-	-	SYM
admet-10	248	21	75	75	NUM
admet-10	248	22	estimating	estimate	VERB
admet-10	248	23	first	first	ADV
admet-10	248	24	in	in	ADP
admet-10	248	25	human	human	PROPN
admet-10	248	26	dose	dose	NOUN
admet-10	248	27	doi	doi	PROPN
admet-10	248	28	:	:	PUNCT
admet-10	248	29	10.5599	10.5599	NUM
admet-10	248	30	/	/	SYM
admet-10	248	31	admet.1.4.10	admet.1.4.10	NOUN
admet-10	248	32	75	75	NUM
admet-10	249	1	[	[	SYM
admet-10	249	2	27	27	NUM
admet-10	249	3	]	]	PUNCT
admet-10	249	4	emea	emea	PROPN
admet-10	249	5	guideline	guideline	NOUN
admet-10	249	6	on	on	ADP
admet-10	249	7	the	the	DET
admet-10	249	8	evaluation	evaluation	NOUN
admet-10	249	9	of	of	ADP
admet-10	249	10	anticancer	anticancer	NOUN
admet-10	249	11	medicinal	medicinal	ADJ
admet-10	249	12	products	product	NOUN
admet-10	249	13	in	in	ADP
admet-10	249	14	man	man	NOUN
admet-10	249	15	2012	2012	NUM
admet-10	249	16	,	,	PUNCT
admet-10	249	17	http://www.ema.europa.eu/docs/en_gb/document_library/scientific_guideline/2013/01/wc5001	http://www.ema.europa.eu/docs/en_gb/document_library/scientific_guideline/2013/01/wc5001	X
admet-10	249	18	37128.pdf	37128.pdf	PROPN
admet-10	249	19	(	(	PUNCT
admet-10	249	20	accessed	access	VERB
admet-10	249	21	26	26	NUM
admet-10	249	22	june	june	PROPN
admet-10	249	23	2013	2013	NUM
admet-10	249	24	)	)	PUNCT
admet-10	249	25	.	.	PUNCT
admet-10	250	1	[	[	X
admet-10	250	2	28	28	NUM
admet-10	250	3	]	]	X
admet-10	250	4	d.r	d.r	PROPN
admet-10	250	5	newell	newell	PROPN
admet-10	250	6	,	,	PUNCT
admet-10	250	7	s.s	s.s	PROPN
admet-10	250	8	.	.	PROPN
admet-10	250	9	burtles	burtle	NOUN
admet-10	250	10	,	,	PUNCT
admet-10	250	11	b.w	b.w	PROPN
admet-10	250	12	.	.	PROPN
admet-10	250	13	fox	fox	PROPN
admet-10	250	14	,	,	PUNCT
admet-10	250	15	d.i	d.i	PROPN
admet-10	250	16	.	.	PROPN
admet-10	250	17	jodrell	jodrell	PROPN
admet-10	250	18	,	,	PUNCT
admet-10	250	19	t.a	t.a	PROPN
admet-10	250	20	.	.	PROPN
admet-10	250	21	connors	connor	NOUN
admet-10	250	22	,	,	PUNCT
admet-10	250	23	british	british	ADJ
admet-10	250	24	journal	journal	PROPN
admet-10	250	25	of	of	ADP
admet-10	250	26	cancer	cancer	NOUN
admet-10	250	27	81	81	NUM
admet-10	250	28	(	(	PUNCT
admet-10	250	29	1999	1999	NUM
admet-10	250	30	)	)	PUNCT
admet-10	250	31	760–768	760–768	NUM
admet-10	250	32	.	.	PUNCT
admet-10	251	1	[	[	X
admet-10	251	2	29	29	NUM
admet-10	251	3	]	]	X
admet-10	251	4	e.a	e.a	PROPN
admet-10	251	5	.	.	PROPN
admet-10	251	6	eisenhauer	eisenhauer	PROPN
admet-10	251	7	,	,	PUNCT
admet-10	251	8	p.j	p.j	PROPN
admet-10	251	9	.	.	PROPN
admet-10	251	10	o’dwyer	o’dwyer	PROPN
admet-10	251	11	,	,	PUNCT
admet-10	251	12	m.	m.	PROPN
admet-10	251	13	christian	christian	PROPN
admet-10	251	14	,	,	PUNCT
admet-10	251	15	j.s	j.s	PROPN
admet-10	251	16	.	.	PROPN
admet-10	251	17	humphrey	humphrey	PROPN
admet-10	251	18	,	,	PUNCT
admet-10	251	19	journal	journal	NOUN
admet-10	251	20	of	of	ADP
admet-10	251	21	clinical	clinical	ADJ
admet-10	251	22	oncology	oncology	NOUN
admet-10	251	23	18	18	NUM
admet-10	251	24	(	(	PUNCT
admet-10	251	25	2000	2000	NUM
admet-10	251	26	)	)	PUNCT
admet-10	251	27	684	684	NUM
admet-10	251	28	-	-	SYM
admet-10	251	29	692	692	NUM
admet-10	251	30	.	.	PUNCT
admet-10	252	1	[	[	X
admet-10	252	2	30	30	NUM
admet-10	252	3	]	]	PUNCT
admet-10	252	4	a.m.	a.m.	NOUN
admet-10	252	5	senderowicz	senderowicz	ADV
admet-10	252	6	,	,	PUNCT
admet-10	252	7	clinical	clinical	ADJ
admet-10	252	8	cancer	cancer	NOUN
admet-10	252	9	research	research	NOUN
admet-10	252	10	16	16	NUM
admet-10	252	11	(	(	PUNCT
admet-10	252	12	2010	2010	NUM
admet-10	252	13	)	)	PUNCT
admet-10	252	14	1719	1719	NUM
admet-10	252	15	-	-	SYM
admet-10	252	16	1725	1725	NUM
admet-10	252	17	.	.	PUNCT
admet-10	253	1	[	[	X
admet-10	253	2	31	31	NUM
admet-10	253	3	]	]	X
admet-10	253	4	n.	n.	NOUN
admet-10	253	5	saigo	saigo	PROPN
admet-10	253	6	,	,	PUNCT
admet-10	253	7	t.	t.	PROPN
admet-10	253	8	tamura	tamura	PROPN
admet-10	253	9	,	,	PUNCT
admet-10	253	10	k.	k.	PROPN
admet-10	253	11	nishio	nishio	PROPN
admet-10	253	12	,	,	PUNCT
admet-10	253	13	cancer	cancer	NOUN
admet-10	253	14	chemotherapy	chemotherapy	NOUN
admet-10	253	15	and	and	CCONJ
admet-10	253	16	pharmacology	pharmacology	NOUN
admet-10	253	17	46	46	NUM
admet-10	253	18	(	(	PUNCT
admet-10	253	19	2000	2000	NUM
admet-10	253	20	)	)	PUNCT
admet-10	253	21	s43	s43	NOUN
admet-10	253	22	-	-	PUNCT
admet-10	253	23	s45	s45	NOUN
admet-10	253	24	.	.	PUNCT
admet-10	254	1	[	[	X
admet-10	254	2	32	32	NUM
admet-10	254	3	]	]	PUNCT
admet-10	254	4	c.	c.	PROPN
admet-10	254	5	le	le	PROPN
admet-10	254	6	tourneau	tourneau	PROPN
admet-10	254	7	,	,	PUNCT
admet-10	254	8	a.	a.	PROPN
admet-10	254	9	stathis	stathis	PROPN
admet-10	254	10	,	,	PUNCT
admet-10	254	11	l.	l.	PROPN
admet-10	254	12	vidal	vidal	PROPN
admet-10	254	13	,	,	PUNCT
admet-10	254	14	m.j	m.j	PROPN
admet-10	254	15	.	.	PROPN
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admet-10	254	17	,	,	PUNCT
admet-10	254	18	l.l	l.l	PROPN
admet-10	254	19	.	.	PROPN
admet-10	254	20	siu	siu	PROPN
admet-10	254	21	,	,	PUNCT
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admet-10	254	23	of	of	ADP
admet-10	254	24	clinical	clinical	ADJ
admet-10	254	25	oncology	oncology	NOUN
admet-10	254	26	28	28	NUM
admet-10	254	27	(	(	PUNCT
admet-10	254	28	2010	2010	NUM
admet-10	254	29	)	)	PUNCT
admet-10	254	30	14011407	14011407	NUM
admet-10	254	31	.	.	PUNCT
admet-10	255	1	[	[	X
admet-10	255	2	33	33	NUM
admet-10	255	3	]	]	PUNCT
admet-10	255	4	j.	j.	PROPN
admet-10	255	5	verweij	verweij	PROPN
admet-10	255	6	,	,	PUNCT
admet-10	255	7	m.l	m.l	PROPN
admet-10	255	8	.	.	PROPN
admet-10	255	9	disis	disis	PROPN
admet-10	255	10	,	,	PUNCT
admet-10	255	11	s.a	s.a	PROPN
admet-10	255	12	.	.	PROPN
admet-10	255	13	cannistra	cannistra	PROPN
admet-10	255	14	,	,	PUNCT
admet-10	255	15	journal	journal	NOUN
admet-10	255	16	of	of	ADP
admet-10	255	17	clinical	clinical	ADJ
admet-10	255	18	oncology	oncology	NOUN
admet-10	255	19	28	28	NUM
admet-10	255	20	(	(	PUNCT
admet-10	255	21	2010	2010	NUM
admet-10	255	22	)	)	PUNCT
admet-10	255	23	4545	4545	NUM
admet-10	255	24	-	-	PUNCT
admet-10	255	25	4546	4546	NUM
admet-10	255	26	.	.	PUNCT
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admet-10	256	2	34	34	NUM
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admet-10	256	4	l.k	l.k	PROPN
admet-10	256	5	.	.	PROPN
admet-10	256	6	seymour	seymour	PROPN
admet-10	256	7	,	,	PUNCT
admet-10	256	8	a.h	a.h	PROPN
admet-10	256	9	.	.	PROPN
admet-10	256	10	calvert	calvert	PROPN
admet-10	256	11	,	,	PUNCT
admet-10	256	12	m.w	m.w	PROPN
admet-10	256	13	.	.	PROPN
admet-10	256	14	lobbezoo	lobbezoo	PROPN
admet-10	256	15	,	,	PUNCT
admet-10	256	16	e.a	e.a	PROPN
admet-10	256	17	.	.	PROPN
admet-10	256	18	eisenhauer	eisenhauer	PROPN
admet-10	256	19	,	,	PUNCT
admet-10	256	20	g.	g.	PROPN
admet-10	256	21	giaccone	giaccone	PROPN
admet-10	256	22	,	,	PUNCT
admet-10	256	23	european	european	PROPN
admet-10	256	24	journal	journal	PROPN
admet-10	256	25	of	of	ADP
admet-10	256	26	cancer	cancer	NOUN
admet-10	256	27	49	49	NUM
admet-10	256	28	(	(	PUNCT
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admet-10	256	30	)	)	PUNCT
admet-10	256	31	1808	1808	NUM
admet-10	256	32	-	-	SYM
admet-10	256	33	1814	1814	NUM
admet-10	256	34	.	.	PUNCT
admet-10	257	1	©	©	PROPN
admet-10	257	2	2013	2013	NUM
admet-10	257	3	by	by	ADP
admet-10	257	4	the	the	DET
admet-10	257	5	authors	author	NOUN
admet-10	257	6	;	;	PUNCT
admet-10	257	7	licensee	licensee	PROPN
admet-10	257	8	iapc	iapc	PROPN
admet-10	257	9	,	,	PUNCT
admet-10	257	10	zagreb	zagreb	PROPN
admet-10	257	11	,	,	PUNCT
admet-10	257	12	croatia	croatia	PROPN
admet-10	257	13	.	.	PUNCT
admet-10	258	1	this	this	DET
admet-10	258	2	article	article	NOUN
admet-10	258	3	is	be	AUX
admet-10	258	4	an	an	DET
admet-10	258	5	open	open	ADJ
admet-10	258	6	-	-	PUNCT
admet-10	258	7	access	access	NOUN
admet-10	258	8	article	article	NOUN
admet-10	258	9	distributed	distribute	VERB
admet-10	258	10	under	under	ADP
admet-10	258	11	the	the	DET
admet-10	258	12	terms	term	NOUN
admet-10	258	13	and	and	CCONJ
admet-10	258	14	conditions	condition	NOUN
admet-10	258	15	of	of	ADP
admet-10	258	16	the	the	DET
admet-10	258	17	creative	creative	ADJ
admet-10	258	18	commons	common	NOUN
admet-10	258	19	attribution	attribution	NOUN
admet-10	258	20	license	license	NOUN
admet-10	258	21	(	(	PUNCT
admet-10	258	22	http://creativecommons.org/licenses/by/3.0/	http://creativecommons.org/licenses/by/3.0/	PROPN
admet-10	258	23	)	)	PUNCT
admet-10	258	24	http://www.ema.europa.eu/docs/en_gb/document_library/scientific_guideline/2013/01/wc500137128.pdf	http://www.ema.europa.eu/docs/en_gb/document_library/scientific_guideline/2013/01/wc500137128.pdf	NOUN
admet-10	258	25	http://www.ema.europa.eu/docs/en_gb/document_library/scientific_guideline/2013/01/wc500137128.pdf	http://www.ema.europa.eu/docs/en_gb/document_library/scientific_guideline/2013/01/wc500137128.pdf	PROPN
admet-10	258	26	http://creativecommons.org/licenses/by/3.0/	http://creativecommons.org/licenses/by/3.0/	PROPN