Registration and design alterations of clinical trials in critical care: a cross-sectional observational study.

PURPOSE

In 2005 the International Committee of Medical Journal Editors issued a requirement that all randomized controlled trials (RCTs) be registered primarily to prevent selective reporting (publication bias). However, registries allow for alterations in study protocol. Changes occurring before (or after) study completion could invalidate the original study intent, leading to publication of misleading conclusions. In RCTs involving critically ill patients, these concerns may be particularly acute because mortality is high and conditions investigated are usually syndromes rather than specific diseases. This study was conducted to estimate the registration rate of RCTs in critical care; and, among registered RCTs, to determine timing of registration and whether sample size or primary outcome were altered.

METHODS

We searched the MEDLINE database for RCTs that began after or continued through July 2005. We determined whether each trial had been registered and, for registered trials, compared registry data to data in the published manuscript.

RESULTS

Approximately two-thirds (66%) of trials were registered. Of these, 66% of registrations occurred after enrolment had commenced. Overall, 6% (5/90) of trials appropriately registered a sample size which was unchanged from the interval between registration and publication, and only 12% (11/90) reported primary outcomes that were both appropriately registered and unchanged.

CONCLUSIONS

Non-registration, or registration after trial initiation, are common in RCTs of critically ill patients. Among registered trials important protocol changes are often made between trial commencement and publication. This study identifies and quantifies the extent of this serious-but correctable-problem for RCTs in critically ill patients.