Accessibility of trial reports for drugs stalling in development: a systematic assessment of registered trials
BMJ 2015; 350 doi: https://doi.org/10.1136/bmj.h1116 (Published 09 March 2015) Cite this as: BMJ 2015;350:h1116
- Amanda Hakala, master’s student1,
- Jonathan Kimmelman, associate professor1,
- Benjamin Carlisle, doctoral student1,
- Georgina Freeman, research assistant1,
- Dean Fergusson, senior scientist2
- 1Studies of Translation, Ethics, and Medicine (STREAM), Biomedical Ethics Unit, Department of Social Studies of Medicine, McGill University, H3A 1X1, Montreal, Canada
- 2Centre for Practice Changing Research, Ottawa Hospital Research Institute, University of Ottawa, K1H 8L6, Ottawa, Canada
- Correspondence to: J Kimmelman jonathan.kimmelman{at}mcgill.ca
- Accepted 20 January 2014
Abstract
Objective To quantify the proportion of trials for unsuccessfully licensed drugs that are not published.
Design A systematic assessment of the availability of published research reports for publicly registered trials testing drugs stalling in clinical development (“stalled drugs”) and drugs receiving regulatory licensure in the same time period (“licensed drugs”).
Data sources Searches of clinicaltrials.gov, Google Scholar, PubMed, Embase, and electronic query of contacts in registries to identify trials and assess publication status.
Eligibility criteria The cohort of licensed drugs consisted of all disease modifying drugs in cancer, cardiovascular disease, or neurological disorders that received Food and Drug Administration licensure during 2005 to 2009 inclusive. The cohort of stalled drugs included unlicensed drugs in the same disease areas that had at least one completed phase III trial before 2009 and no evidence of any clinical trial activity after 31 December 2009. Inclusion criteria for registered trials advanced into publication searching were an intervention tested in a disease modifying, phase II, III, or IV trial registered on clinicaltrials.gov, with enrolment of at least one patient, that reported primary outcome collection end date between 1 January 2006 and 31 December 2008.
Results The unadjusted publication proportion for registered trials of licensed drugs was 75% (72/96) versus 37% (30/81) for stalled drugs. The adjusted hazard ratio for publication was 2.7 (95% confidence interval 1.7 to 4.3) in favour of licensed drug trials. Higher publication rates for licensed drug trials were observed regardless of disease type, sponsorship, trial phase, and geography. The rate of non-publication of stalled drug trials was significantly higher for studies that did not complete enrolment compared with licensed drug trials. A total of 20 135 patients participated in trials of stalled drugs that were never published.
Conclusions Much of the information collected in unsuccessful drug trials is inaccessible to the broader research and practice communities. These findings provide an evidence base and rationale for policy reforms aimed at promoting transparency, ethics, and accountability in clinical research.
Footnotes
Contributors: JK conceived the idea for the article and performed a preliminary study of trial availability for licensed drugs. DF helped JK with study design and provided statistical planning and analysis. BC and GF in consultation with JK elaborated a search strategy and built the cohort of stalled drugs. GF and AH constructed the trial cohorts. AH performed the literature searches. GF double coded the literature search for 10% of the trials in each cohort. BC constructed a database to handle email queries. AH queried trial contacts. JK and DF designed and AH and DF performed the analysis of the data. AH and JK wrote the article. All authors edited, reviewed, and approved the final version. JK is the guarantor of the study.
Funding: This work was funded by the Canadian Institutes of Health Research (EOG111391). The study sponsor played no role in study design; collection, analysis, or interpretation of data; writing of the article; or the decision to submit the manuscript for publication. All researchers are independent from the funder.
Competing interests: All authors have completed the ICMJE uniform disclosure form at http://www.icmje.org/coi_disclosure.pdf. DF and JK declare grants from the Canadian Institutes of Health Research for the submitted work. JK also declares grants from Genome Canada. All authors declare no financial relationships with any organisations that might have an interest in the submitted work in the previous three years and no relationships or activities that could appear to have influenced the submitted work.
Ethical approval: Our study received ethical approval from the McGill University Institutional Review Board. Contacts queried about trial publication status were informed that response would be interpreted as consent to participate in the study.
Transparency: The guarantor affirms that this manuscript is an honest, accurate, and transparent account of the study being reported; that no important aspects of the study have been omitted; and that any discrepancies from the study as planned have been explained.
Data access: All authors had full access to the data and can be held responsible for its accuracy. The corresponding author agrees to share all data files upon request.
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