UC5:Assigning of Epoch after treatment discontinuation (NS)

Study epochs per protocol:

Screening Treatment Follow up Randomization, Treatment start End of treatment, Date of last trt End of study, consent withdraw

UC5: (cont.) subject information

• • • • • • CRF pages: end of treatment, FU, end of study Subject has got 2 cycles. Last TRTDTC=2014-02-01 Cycle 3 should start at 2014-02-21, but subject has AE, thus treatment delay, No bettering after 14 days, Lab visit, EG Visit performed. => Physician decision to discontinue treatment Subject comes to visit and decide not to go to FU, but to withdraw consent at 2014-03-14, so no FU observation and data collection, end of study. Q: Which epoch and VISITNUM to assign to LB and EG visit in delay period?

Question

• On which level should we handle treatment delay period: EPOCH or ELEMENT?

Definition from CDISC SDTM

• Epoch: As part of the design of a trial, the planned period of subjects' participation in the trial is divided into Epochs. Each Epoch is a period of time that serves a purpose in the trial as a whole. That purpose will be at the level of the primary objectives of the trial. Typically, the purpose of an Epoch will be to expose subjects to a treatment, or to prepare for such a treatment period (e.g., determine subject eligibility, wash out previous treatments) or to gather data on subjects after a treatment has ended.

Definition from CDISC SDTM

• Element: An Element is a basic building block in the trial design. It involves administering a planned intervention, which may be treatment or no treatment, during a period of time. Elements for which the planned intervention is "no treatment" would include Elements for screening, washout, and follow up.

Definition from CDISC SDTM

• “If TAETORD and/or EPOCH are added, then the values must be those at the start of the visit” • Chapter 5, “SV”, P3 5. Judgment will also have to be used in deciding how to represent a subject's experience if an Element does not proceed or end as planned. For instance, the plan might identify a trial Element which is to start with the first of a series of 5 daily doses and end after 1 week, when the subject transitions to the next treatment Element. If the subject actually started the next treatment Epoch [see

Section 7 - Introduction: 7.1.2, Definitions Of Trial Design

Concepts] after 4 weeks, the sponsor will have to decide whether to

represent this as an abnormally long Element, or as a normal

Element plus an unplanned non-treatment Element.

Chapter 5, “SE”, P3

Handling on EPOCH level

Study epochs per protocol:

Screening Treatment Follow up Randomization, Treatment start End of treatment, Date of last trt End of study, consent withdraw

Epoch Level: Subject time axis

No FU information collected in Original EDC DB

Last treatment 2014-02-01 Consent W.

2014-03-14 LB and EG visit Screening Treatment Follow up?

Randomization Treatment start End of treatment, Date of last trt End of study, consent withdraw

SE

How it looks in the data (Option 1)

ROW 1 2 3 ETCD SCR TRT FU SESTDTC 2014-01-01 SEENDTC 2014-01-10 2014-01-10 2014-02-01 2014-02-01 2014-03-14 SEUPDES EPOCH SCREENING

TREATMENT

FOLLOW UP

LB SV ROW 1 2 How it looks in the data (cont.) EPOCH TREATMENT FOLLOW UP

VISIT

Cycle 2 Cycle 3 2 3 VISITNUM LBDTC 2014-02-01

2014-03-07

ROW 1 2 3 4 EPOCH TREATMENT FOLLOW-UP ???

FOLLOW-UP VISIT Cycle 2 Cycle 3 End of Treatment End of Study VISITNUM SVDY SVDTC 2014-02-01 2 3 2014-02-21 99 2014-03-14 999 2014-03-14 Date, where decision to stop treatment and study was made (last subject visit) DS ROW 1 2 3 DSCAT PROTOCOL MILESTONE DISPOSITION EVENT DISPOSITION EVENT DSSCAT DSDECODE RANDOMIZATI ON END OF TREATMENT AE END OF STUDY CONCENT WITHDRAWL EPOCH DSSTDTC SCREENING 2013-11-11 ??? 2014-02-01 FOLLOW-UP 2014-03-14 Date of last medication administration

Question to team

How to populate EPOCH for „End of Treatment“ (SV obs 3, and DS obs 2) for that case: 1. „FOLLOW UP“ in SV and DS (discrepancy with protocol schedule and SDTM IG as end of treament closed to treatment epoch)?

2. „TREATMENT“ in SV and DS (discrepancy by date and sorting order for SV, discrepancy to SE)?

3. „FOLLOW UP“ in SV and „TREATMENT“ in DS (agreement with SE based on date, but different EPOCH description for same event)?

4. Leave blank?

Element level: Subject time axis

No FU information collected in Original EDC DB

Last treatment 2014-02-01 Consent W.

2014-03-14 LB and EG visit Screening Treatment Unplanned SE, Treatment delay?

Randomization Treatment start End of treatment, Date of last trt End of study, consent withdraw

SE

How it looks in the data (Option 2)

ROW 1 2 3 4 ETCD SCR TRT UNPL

FU

SESTDTC 2014-01-01 SEENDTC 2014-01-10 2014-01-10 2014-02-01 2014-02-01 2014-03-14

2014-03-14 2014-03-14

SEUPDES EPOCH SCREENING TREATMENT Treatment delay TREATMENT

FOLLOW UP

LB SV ROW 1 2 How it looks in the data (cont.) EPOCH TREATMENT TREATMENT

VISIT

Cycle 2 Cycle 3 2 3 VISITNUM LBDTC 2014-02-01

2014-03-07

ROW 1 2 3 4 EPOCH TREATMENT TREATMENT TREATMENT FOLLOW-UP VISIT Cycle 2 Cycle 3 End of Treatment End of Study VISITNUM SVDY SVDTC 2014-02-01 2 3 2014-02-21 99 2014-03-14 999 2014-03-14 Date, where decision to stop treatment and study was made (last subject visit) DS ROW 1 2 3 DSCAT PROTOCOL MILESTONE DISPOSITION EVENT DISPOSITION EVENT DSSCAT DSDECODE RANDOMIZATI ON END OF TREATMENT AE END OF STUDY CONCENT WITHDRAWL EPOCH DSSTDTC SCREENING 2013-11-11 TREATMENT 2014-02-01

FOLLOW-UP

2014-03-14 Date of last medication administration

Questions to team

• • Can we consider Treatment delay as Unplanned Element if it is acceptable according to Protocol Do we need to define „FU“ Element /Epoch for this case in SE and other domains?

Questions to FDA

• • • Is variable EPOCH expected in SV and DS domains as well?

Is discrepancy between scheduled visit number and EPOCH acceptable if described in RG? ( considering option 1 as for other subjects Cycle 3 will correspond to „TREATMENT“ EPOCH ) Would it be acceptable to have EPOCH blank with description in Reviewer Guide?