Pre-registration
Pre-registration is the public recording of a trial's plan, including its primary outcomes, in a trial registry such as ClinicalTrials.gov before the first participant is enrolled, so that readers can check the published report against the plan.
What it means in practice
In September 2004 the International Committee of Medical Journal Editors changed its policy: its journals would consider trials for publication only if they had been registered before the first participant was enrolled [1]. CONSORT says this led to a dramatic increase in the number of registered trials [1].
The CONSORT 2025 reporting guideline, a 30-item checklist, asks trial reports to give the registry name, the identifying number with a URL, and the date of registration [2]. It also asks where the trial protocol and statistical analysis plan can be accessed [2]. The SPIRIT 2025 guideline calls the protocol of a randomized trial the foundation for study planning, conduct, reporting and external review [3].
Why it matters when reading nootropics research
Comparing a trial's plan with its paper shows whether outcomes were switched. In a study of 102 trials approved by ethics committees in Copenhagen and Frederiksberg, Denmark, 62% had at least one primary outcome that was changed, introduced or omitted between protocol and publication [4]. Statistically significant efficacy outcomes were more likely to be fully reported than nonsignificant ones (pooled odds ratio 2.4) [4]. The authors concluded that planned trials should be registered and their protocols made public before the trial is completed [4].
Among large trials of drugs or dietary supplements with cardiovascular outcomes, funded by the US National Heart, Lung, and Blood Institute, 17 of 30 (57%) published before 2000 reported a significant benefit on the primary outcome, compared with 2 of 25 (8%) published after 2000 [5]. Pre-registration on ClinicalTrials.gov was strongly associated with this shift toward null results, and the authors suggest that declaring outcomes in advance may have contributed [5].
A supplement trial's registry record can be compared with its paper to see whether the primary outcome stayed the same.
References
- Moher D, Hopewell S, Schulz KF, et al. CONSORT 2010 explanation and elaboration: updated guidelines for reporting parallel group randomised trials. BMJ. 2010.
- Hopewell S, Chan AW, Collins GS, et al. CONSORT 2025 statement: Updated guideline for reporting randomised trials. PLoS Med. 2025.
- Chan AW, Boutron I, Hopewell S, et al. SPIRIT 2025 statement: Updated guideline for protocols of randomised trials. PLoS Med. 2025.
- Chan AW, Hróbjartsson A, Haahr MT, et al. Empirical evidence for selective reporting of outcomes in randomized trials: comparison of protocols to published articles. JAMA. 2004.
- Kaplan RM, Irvin VL. Likelihood of Null Effects of Large NHLBI Clinical Trials Has Increased over Time. PLoS One. 2015.