title: Specific barriers to the conduct of randomized trials.
abstract: Large randomized trials are required to provide reliable evidence of the typically moderate benefit of most interventions. To be affordable, such trials need to be simple; to be widely applicable, they need to be close to normal clinical practice. However, current regulations and guidelines have hugely increased trial complexity, effectively becoming barriers to their design and conduct. Key barriers include inadequate funding, overly complex regulations producing needlessly complex trial procedures, excessive monitoring, over restrictive interpretation of privacy laws without evidence of subject benefit, and inadequate understanding of methodology. Complex regulations result in multiple ethics approvals for a multi-center study, unnecessary complexity in the study protocol, delays in securing regulatory approval, and cumbersome regulatory procedures, even for drugs widely used in clinical practice. The type of detailed safety monitoring currently needed in trials of new drugs is being applied indiscriminately to all studies including a simpler and basic level of monitoring that constitutes good practice in most trials could be agreed on, with that level being exceeded only in specific instances. More evidence about the pros and cons of alternative approaches to data quality monitoring would help inform this process. Complex procedures in the form of multiple-page consent forms, overzealous monitoring of side effects and adverse events, source data verification, and over-restrictive approaches to protocol amendments, can impede, rather than facilitate, trial objectives. Finally, further education on the nuances and functions of randomisation would facilitate trial conduct, and reduce the need for burdensome complexity. A radical re-evaluation of existing trial guidelines is needed, based on a clear understanding of the important principles of randomized trials, with the objective of eliminating unnecessary documentation and reporting without sacrificing validity or safety. Researchers should encourage public debate about how best to strike the balance between regulation and cost.
authors.affiliation: University of Leeds, UK.
authors.forename: Lelia
authors.initials: L
authors.lastname: Duley
authors.forename: Karen
authors.initials: K
authors.lastname: Antman
authors.forename: Joseph
authors.initials: J
authors.lastname: Arena
authors.forename: Alvaro
authors.initials: A
authors.lastname: Avezum
authors.forename: Mel
authors.initials: M
authors.lastname: Blumenthal
authors.forename: Jackie
authors.initials: J
authors.lastname: Bosch
authors.forename: Sue
authors.initials: S
authors.lastname: Chrolavicius
authors.forename: Timoa
authors.initials: T
authors.lastname: Li
authors.forename: Stephanie
authors.initials: S
authors.lastname: Ounpuu
authors.forename: Analia Cristina
authors.initials: AC
authors.lastname: Perez
authors.forename: Peter
authors.initials: P
authors.lastname: Sleight
authors.forename: Robbyna
authors.initials: R
authors.lastname: Svard
authors.forename: Robert
authors.initials: R
authors.lastname: Temple
authors.forename: Yannis
authors.initials: Y
authors.lastname: Tsouderous
authors.forename: Carla
authors.initials: C
authors.lastname: Yunis
authors.forename: Salim
authors.initials: S
authors.lastname: Yusuf
mesh_terms: D003219:Confidentiality; D032962:Consent Forms; D017041:Ethics Committees; D006801:Humans; D015337:Multicenter Studies as Topic / Q000191:economics / Q000379:methods; D017410:Practice Guidelines as Topic; D016032:Randomized Controlled Trials as Topic / Q000191:economics / Q000331:legislation & jurisprudence* / Q000379:methods*