SEND Example.In vivo Study Design with Recovery Period

This example assumes a design in which the applicant-defined protocol specifies the following information. All subjects are to be screened for 7 days prior to randomization into 3 protocol groups:

Group 1 is a control group of 20 subjects, 10 male and 10 female, dosed with vehicle once per day for 28 days. After 28 days, 5 subjects/sex will be terminated and the other half will go on to a 7-day recovery period prior to termination.
Group 2 is a low-dose group of 20 subjects, 10 male and 10 female, dosed at 100 mg/kg once per day for 28 days. After 28 days, 5 subjects/sex will be terminated and the other half will go on to a 7-day recovery period prior to termination.
Group 3 is a high-dose group of 20 subjects, 10 male and 10 female, dosed at 500 mg/kg once per day for 28 days. After 28 days, 5 subjects/sex will be terminated and the other half will go on to a 7-day recovery period prior to termination.

Group Number	Group Label	Dose Level	Number of Animals (Both Sexes Combined)
Group Number	Group Label	Dose Level	Nonrecovery	Recovery
1	Group 1, Control	Vehicle Control	10	10
2	Group 2, 100 mg/kg	100 mg/kg/day	10	10
3	Group 3, 500 mg/kg	500 mg/kg/day	10	10

There are no other experimental factors of interest specified in the study design. In this case, the design consists of 6 trial arms, because there are 6 distinct sequences of elements, as depicted in the following figure.

Figure. Example Trial 1 Design

Trial Elements

This example includes the start and end rule for the recovery element starting after last dose of the drug or vehicle.

te.xpt

Row	STUDYID	DOMAIN	ETCD	ELEMENT	TESTRL	TEENRL	TEDUR
1	TDM1	TE	SCRN	Screen	Start of Pretreatment	1 week after start of Element	P7D
2	TDM1	TE	TRT01	Vehicle Control	First day of dosing with vehicle control	28 days after start of Element	P28D
3	TDM1	TE	TRT02	100 mg/kg Drug A, once daily	First day of dosing with 100 mg/kg Drug A	28 days after start of Element	P28D
4	TDM1	TE	TRT03	500 mg/kg Drug A, once daily	First day of dosing with 500 mg/kg Drug A	28 days after start of Element	P28D
5	TDM1	TE	RECO	Recovery	First day of Recovery	7 days after start of Element	P7D

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Trial Arms

The 6 trial arms of this study can be depicted as follows:

ta.xpt

Row	STUDYID	DOMAIN	ARMCD	ARM	TAETORD	ETCD	ELEMENT	TABRANCH	EPOCH
1	TDM1	TA	01	Control	1	SCRN	Screen	Randomized to Group 1	PRE-TREATMENT
2	TDM1	TA	01	Control	2	TRT01	Vehicle Control		TREATMENT
3	TDM1	TA	01R	Control w/ Recovery	1	SCRN	Screen	Randomized to Group 1, planned for recovery	PRE-TREATMENT
4	TDM1	TA	01R	Control w/ Recovery	2	TRT01	Vehicle Control		TREATMENT
5	TDM1	TA	01R	Control w/ Recovery	3	RECO	Recovery		RECOVERY
6	TDM1	TA	02	Low Dose	1	SCRN	Screen	Randomized to Group 2	PRE-TREATMENT
7	TDM1	TA	02	Low Dose	2	TRT02	100 mg/kg Drug A		TREATMENT
8	TDM1	TA	02R	Low Dose w/ Recovery	1	SCRN	Screen	Randomized to Group 2, planned for recovery	PRE-TREATMENT
9	TDM1	TA	02R	Low Dose w/ Recovery	2	TRT02	100 mg/kg Drug A		TREATMENT
10	TDM1	TA	02R	Low Dose w/ Recovery	3	RECO	Recovery		RECOVERY
11	TDM1	TA	03	High Dose	1	SCRN	Screen	Randomized to Group 3	PRE-TREATMENT
12	TDM1	TA	03	High Dose	2	TRT03	500 mg/kg Drug A		TREATMENT
13	TDM1	TA	03R	High Dose w/ Recovery	1	SCRN	Screen	Randomized to Group 3, planned for recovery	PRE-TREATMENT
14	TDM1	TA	03R	High Dose w/ Recovery	2	TRT03	500 mg/kg Drug A		TREATMENT
15	TDM1	TA	03R	High Dose w/ Recovery	3	RECO	Recovery		RECOVERY

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Trial Sets

As noted, there are 6 distinct trial sets. The experimental factors of interest are the dose level to be received during the treatment period and whether the subjects are planned for termination on day 28 or will enter a recovery period.

In this example, the applicant is providing the arm code, applicant-defined group code, group label, set label, dose level and units, control type, and planned number of males and females for each set.

tx.xpt

Row	STUDYID	DOMAIN	SETCD	SET	TXSEQ	TXPARMCD	TXPARM	TXVAL
1	TDM1	TX	1NR	Control Group, Vehicle Control once daily, Nonrecovery	1	ARMCD	Arm Code	01
2	TDM1	TX	1NR	Control Group, Vehicle Control once daily, Nonrecovery	2	SPGRPCD	applicant-Defined Group Code	1
3	TDM1	TX	1NR	Control Group, Vehicle Control once daily, Nonrecovery	3	GRPLBL	Group Label	Group 1, Control
4	TDM1	TX	1NR	Control Group, Vehicle Control once daily, Nonrecovery	4	SETLBL	Set Label	Group 1, Control - Nonrec
5	TDM1	TX	1NR	Control Group, Vehicle Control once daily, Nonrecovery	5	TRTDOS	Dose Level	0
6	TDM1	TX	1NR	Control Group, Vehicle Control once daily, Nonrecovery	6	TRTDOSU	Dose Units	mg/kg/day
7	TDM1	TX	1NR	Control Group, Vehicle Control once daily, Nonrecovery	7	TCNTRL	Control Type	VEHICLE CONTROL
8	TDM1	TX	1NR	Control Group, Vehicle Control once daily, Nonrecovery	8	PLANMSUB	Planned Number of Male Subjects	5
9	TDM1	TX	1NR	Control Group, Vehicle Control once daily, Nonrecovery	9	PLANFSUB	Planned Number of Female Subjects	5
10	TDM1	TX	1R	Control Group, Vehicle Control once daily, Recovery	10	ARMCD	Arm Code	01R
11	TDM1	TX	1R	Control Group, Vehicle Control once daily, Recovery	11	SPGRPCD	Applicant-Defined Group Code	1
12	TDM1	TX	1R	Control Group, Vehicle Control once daily, Recovery	12	GRPLBL	Group Label	Group 1, Control
13	TDM1	TX	1R	Control Group, Vehicle Control once daily, Recovery	13	SETLBL	Set Label	Group 1, Control - Rec
14	TDM1	TX	1R	Control Group, Vehicle Control once daily, Recovery	14	TRTDOS	Dose Level	0
15	TDM1	TX	1R	Control Group, Vehicle Control once daily, Recovery	15	TRTDOSU	Dose Units	mg/kg/day
16	TDM1	TX	1R	Control Group, Vehicle Control once daily, Recovery	16	TCNTRL	Control Type	VEHICLE CONTROL
17	TDM1	TX	1R	Control Group, Vehicle Control once daily, Recovery	17	PLANMSUB	Planned Number of Male Subjects	5
18	TDM1	TX	1R	Control Group, Vehicle Control once daily, Recovery	18	PLANFSUB	Planned Number of Female Subjects	5
19	TDM1	TX	2NR	Low-Dose Group, 100 mg/kg Drug a once daily, Nonrecovery	19	ARMCD	Arm Code	02
20	TDM1	TX	2NR	Low-Dose Group, 100 mg/kg Drug a once daily, Nonrecovery	20	SPGRPCD	Applicant-Defined Group Code	2
21	TDM1	TX	2NR	Low-Dose Group, 100 mg/kg Drug a once daily, Nonrecovery	21	GRPLBL	Group Label	Group 2, 100 mg/kg
22	TDM1	TX	2NR	Low-Dose Group, 100 mg/kg Drug a once daily, Nonrecovery	22	SETLBL	Set Label	Group 2, 100 mg/kg - Nonrec
23	TDM1	TX	2NR	Low-Dose Group, 100 mg/kg Drug a once daily, Nonrecovery	23	TRTDOS	Dose Level	100
24	TDM1	TX	2NR	Low-Dose Group, 100 mg/kg Drug a once daily, Nonrecovery	24	TRTDOSU	Dose Units	mg/kg/day
25	TDM1	TX	2NR	Low-Dose Group, 100 mg/kg Drug a once daily, Nonrecovery	25	PLANMSUB	Planned Number of Male Subjects	5
26	TDM1	TX	2NR	Low-Dose Group, 100 mg/kg Drug a once daily, Nonrecovery	26	PLANFSUB	Planned Number of Female Subjects	5
27	TDM1	TX	2R	Low-Dose Group, 100 mg/kg Drug a once daily, Recovery	27	ARMCD	Arm Code	02R
28	TDM1	TX	2R	Low-Dose Group, 100 mg/kg Drug a once daily, Recovery	28	SPGRPCD	Applicant-Defined Group Code	2
29	TDM1	TX	2R	Low-Dose Group, 100 mg/kg Drug a once daily, Recovery	29	GRPLBL	Group Label	Group 2, 100 mg/kg
30	TDM1	TX	2R	Low-Dose Group, 100 mg/kg Drug a once daily, Recovery	30	SETLBL	Set Label	Group 2, 100 mg/kg - Rec
31	TDM1	TX	2R	Low-Dose Group, 100 mg/kg Drug a once daily, Recovery	31	TRTDOS	Dose Level	100
32	TDM1	TX	2R	Low-Dose Group, 100 mg/kg Drug a once daily, Recovery	32	TRTDOSU	Dose Units	mg/kg/day
33	TDM1	TX	2R	Low-Dose Group, 100 mg/kg Drug a once daily, Recovery	33	PLANMSUB	Planned Number of Male Subjects	5
34	TDM1	TX	2R	Low-Dose Group, 100 mg/kg Drug a once daily, Recovery	34	PLANFSUB	Planned Number of Female Subjects	5
35	TDM1	TX	3NR	High-Dose Group, 500 mg/kg Drug a once daily, Nonrecovery	35	ARMCD	Arm Code	03
36	TDM1	TX	3NR	High-Dose Group, 500 mg/kg Drug a once daily, Nonrecovery	36	SPGRPCD	Applicant-Defined Group Code	3
37	TDM1	TX	3NR	High-Dose Group, 500 mg/kg Drug a once daily, Nonrecovery	37	GRPLBL	Group Label	Group 3, 500 mg/kg
38	TDM1	TX	3NR	High-Dose Group, 500 mg/kg Drug a once daily, Nonrecovery	38	SETLBL	Set Label	Group 3, 500 mg/kg - Nonrec
39	TDM1	TX	3NR	High-Dose Group, 500 mg/kg Drug a once daily, Nonrecovery	39	TRTDOS	Dose Level	500
40	TDM1	TX	3NR	High-Dose Group, 500 mg/kg Drug a once daily, Nonrecovery	40	TRTDOSU	Dose Units	mg/kg/day
41	TDM1	TX	3NR	High-Dose Group, 500 mg/kg Drug a once daily, Nonrecovery	41	PLANMSUB	Planned Number of Male Subjects	5
42	TDM1	TX	3NR	High-Dose Group, 500 mg/kg Drug a once daily, Nonrecovery	42	PLANFSUB	Planned Number of Female Subjects	5
43	TDM1	TX	3R	High-Dose Group, 500 mg/kg Drug a once daily, Recovery	43	ARMCD	Arm Code	03R
44	TDM1	TX	3R	High-Dose Group, 500 mg/kg Drug a once daily, Recovery	44	SPGRPCD	Applicant-Defined Group Code	3
45	TDM1	TX	3R	High-Dose Group, 500 mg/kg Drug a once daily, Recovery	45	GRPLBL	Group Label	Group 3, 500 mg/kg
46	TDM1	TX	3R	High-Dose Group, 500 mg/kg Drug a once daily, Recovery	46	SETLBL	Set Label	Group 3, 500 mg/kg - Rec
47	TDM1	TX	3R	High-Dose Group, 500 mg/kg Drug a once daily, Recovery	47	TRTDOS	Dose Level	500
48	TDM1	TX	3R	High-Dose Group, 500 mg/kg Drug a once daily, Recovery	48	TRTDOSU	Dose Units	mg/kg/day
49	TDM1	TX	3R	High-Dose Group, 500 mg/kg Drug a once daily, Recovery	49	PLANMSUB	Planned Number of Male Subjects	5
50	TDM1	TX	3R	High-Dose Group, 500 mg/kg Drug a once daily, Recovery	50	PLANFSUB	Planned Number of Female Subjects	5

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SEND Example.In vivo Study Design with Recovery Period