biostudies-literatureLlewellyn-Bennett RNational Centre for the Replacement, Refinement and Reduction of Animals in ResearchMedical Research CouncilAlzheimers Research UKNational Institute for Health Research (NIHR)Alzheimer's SocietyRoyal College of Surgeons of England298https://www.ebi.ac.uk/biostudies/studies/S-EPMC5975470biostudies-literatureUnknown19(1)<h4>Background</h4>Randomised controlled clinical trials typically have a relatively brief in-trial follow-up period which can underestimate safety signals and fail to detect long-term hazards, which may take years to appear. Extended follow-up after the scheduled closure of the trial allows detection of both persistent or enhanced beneficial effects following cessation of study treatment (i.e. a legacy effect) and the emergence of possible adverse effects (e.g. development of cancer).<h4>Methods</h4>A systematic review was conducted following PRISMA guidelines to qualitatively compare post-trial follow-up methods used in large randomised controlled trials. Five bibliographic databases, including Medline and the Cochrane Library, and one trial registry were searched. All large randomised cTrialsPost-trial follow-up methodology in large randomised controlled trials: a systematic review.PMC5975470MC_U137686861MR/L023784/2CL-2015-16-001HDR-4002Research FellowshipART-PPG2005A-2151G0800701/1ARUK-PPG2014A-8Hainsworth AHBowman LEdwards DRoberts NLlewellyn-Bennett RBulbulia RfalsePost-trial follow-up methodology in large randomised controlled trials: a systematic review.<h4>Background</h4>Randomised controlled clinical trials typically have a relatively brief in-trial follow-up period which can underestimate safety signals and fail to detect long-term hazards, which may take years to appear. Extended follow-up after the scheduled closure of the trial allows detection of both persistent or enhanced beneficial effects following cessation of study treatment (i.e. a legacy effect) and the emergence of possible adverse effects (e.g. development of cancer).<h4>Methods</h4>A systematic review was conducted following PRISMA guidelines to qualitatively compare post-trial follow-up methods used in large randomised controlled trials. Five bibliographic databases, including Medline and the Cochrane Library, and one trial registry were searched. All large randomised c2018-01-01T00:00:00Z2018 May2025-04-18T17:31:43.136Z2019-03-26T23:39:39ZS-EPMC59754702984377410.1186/s13063-018-2653-0