Flexible trial design in practice - stopping arms for lack-of-benefit and adding research arms mid-trial in STAMPEDE: a multi-arm multi-stage randomized controlled trial

Table 2 Planned actions and timelines when accrual is stopped to trial arms

Action required	Timelines
	Safety	LOB
Notify sites in writing of IDMC meeting date to pre-warn	-28 d	-28 d
Circulate prior letter from regulatory agency confirming that stopping early for LOB is not a substantial amendment, but part of trial design	-28 d	-28 d
IDMC meeting	-7 d	-7 d
IDMC notes and recommendations finalised	(<1 w)	(<1 w)
TSC meeting: stop / continue decision for each research arm	Day 0	Day 0
Turn off randomisation to arms stopping early for safety	<24 h	<1 w
Notify centres by email; patients to ignore irrelevant parts of PIS	<24 h	<24 h
Notify relevant industry partners	<24 h	<24 h
Notify TMG members	<24 h	<24 h
Alert trials unit staff to potential queries	<24 h	<48 h
Phone all site PIs. Instructed to hand-amend PIS and CF. Updated documentation to follow	<1 w	<1 w
Protocol and documents updated and agreed by TMG	<1 w	<1 w
Summary information for patients	<2 w	<2 w
Notify ethics committee and regulatory agency (for information only)	<2 w	<2 w
Detailed discussions with industry partners	<1 m	<1 m
TMG review of processes	<1 m	<1 m

Key: LOB = lack-of-benefit; IDMC = Independent Data Monitoring Committee; TSC = Trial Steering Committee; TMG = Trial Management Group; PIS = patient information sheet; CF = consent form; h = hour; w = week.
Note: the observed timelines broadly followed these plans.

ISSN: 1745-6215