An-Wen Chan,1,2 Annukka Pello,3 Jessica Kitchen,1 Anna Axentiev,1 Jorma Virtanen,4 Annie Liu,1 Elina Hemminki5
To evaluate adherence to trial registration and its association with subsequent publication and selective reporting of primary outcomes in an unselected cohort of clinical trials.
This was an inception cohort study of all initiated clinical trial protocols approved in 2002 (n=135) and 2007 (n=113) by the research ethics committee for the region of Helsinki and Uusimaa, Finland. We identified registry records and articles published up to February 2017 using keywords to search trial registries, PubMed, EMBASE, and Google. Trial characteristics (approval year, funding, sample size, intervention type, number of arms and centers) and outcomes were abstracted from each protocol, registry record, and publication. Using descriptive statistics and multivariable logistic regression, we determined the rates and predictors of registration and publication; the proportion of trials with discrepant primary outcomes in the protocol compared with the registry and publication; and the association between registration and subsequent publication without discrepant primary outcomes. Discrepancies were defined as (1) a new primary outcome being reported that was not specified as primary in the protocol; or (2) a protocol-defined primary outcome being omitted or downgraded (reported as secondary or unspecified) in the registry or published article.
Registration rates increased from 0% (0 of 135) for trials approved in 2002 to 61% (69 of 113) in 2007. Overall, 130 of 248 of all trials (52%) were published (publication years 2003 through 2016); 16 of 69 registered trials (23%) had discrepancies in primary outcomes defined in the registry compared with the protocol, while 24 of 116 published trials (21%) had discrepancies in primary outcomes between the published article and the protocol. Among trials approved in 2007, trial registration was significantly associated with subsequent publication (68% of registered trials vs 39% of unregistered trials; adjusted odds ratio [aOR], 4.5; 95% CI, 1.1-18). Registered trials were also significantly more likely than unregistered trials to be subsequently published with the same primary outcomes defined in the published article compared with the protocol (64% vs 25%; aOR, 5.8; 95% CI, 1.4-24).
Clinical trials are not only often unregistered and unpublished but also discrepant in the reporting of primary outcomes across different information sources. These major deficiencies impair transparency and facilitate the biased reporting of trial results, which can be mitigated through adherence to trial registration. Journal editors, legislators, funding agencies, regulators, research ethics committees, and sponsors should implement and enforce policies mandating registration and public access to full protocols for all clinical trials.
1Women’s College Research Institute, Women’s College Hospital, Toronto, Ontario, Canada, firstname.lastname@example.org; 2Department of Medicine, University of Toronto, Ontario, Canada; 3Faculty of Medicine, University of Helsinki, Helsinki, Finland; 4Faculty of Medicine, University of Oulu, Oulu, Finland; 5THL (National Institute for Health and Welfare), Helsinki, Finland
Conflict of Interest Disclosures:
This project was supported by the Canadian Institutes of Health Research Dissemination Events (grants MET 117434 and MET 133851) and the Academy of Finland (grant No. 28356).
Role of the Funder/Sponsor:
The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the abstract.