A study published in JAMA found that the prospective registration of clinical trials is associated with publication without discrepancies in primary outcomes.
An-Wen Chan, MD, DPhil, of the Women’s College Research Institute, University of Toronto in Canada, and colleagues conducted a cohort study of all initiated clinical trial protocols approved in 2007 by the research ethics committee for the region of Helsinki and Uusimaa, Finland.
The researchers included registry records and articles published up to February 2017. They used descriptive statistics and multivariable logistic regression to determine the prevalence of and variables associated with prospective registration, the proportion of trials with one or more discrepancies between the protocol and the registry and publications, and the association between prospective registration and subsequent publication without discrepancies in the primary outcomes compared with the protocol. Discrepancies were defined as a new primary outcome being reported that was not specified as such in the protocol or as a primary outcome defined in the protocol that was left out or demoted to a secondary or unspecified outcome in the registry or publication.
Dr Chan and colleagues found that in 113 trials, 61% were prospectively registered and 57% were published. The likelihood of trial registration was increased in trials involving drug or biologic interventions and larger sample sizes.
Of the protocols, 20% failed to specify a primary outcome, and discrepancies were found in at least 1 primary outcome defined in the registry for 23% of prospectively registered trials compared with the protocol, while 16% of published trials with defined primary outcomes had discrepancies between publication and protocol. Among unregistered trials, 55% had discrepancies between the protocol and publication, in contrast to 6% of registered trials (P <.001).
Prospectively registered trials were significantly more likely to be published (68%) compared with unregistered trials (39%). Furthermore, registered trials were also significantly more likely than unregistered trials to be published with the same primary outcomes as defined in the protocol (64% vs 25%, respectively).
The investigators called for original protocols and amendments to be made publicly available so that editors, peer reviewers, and readers can readily identify changes to protocol-defined outcomes.
Chan A-W, Pello A, Kitchen J, et al. Association of trial registration with reporting of primary outcomes in protocols and publications. JAMA. 2017;318(17):1709-1711.