Accessibility of trial reports for drugs stalling in development: a systematic assessment of registered trials.
OBJECTIVE
To quantify the proportion of trials for unsuccessfully licensed drugs that are not published.


METHODS
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").


METHODS
Searches of clinicaltrials.gov, Google Scholar, PubMed, Embase, and electronic query of contacts in registries to identify trials and assess publication status.


METHODS
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.
Studies of Translation, Ethics, and Medicine (STREAM), Biomedical Ethics Unit, Department of Social Studies of Medicine, McGill University, H3A 1X1, Montreal, Canada.
Amanda
A
Hakala
Studies of Translation, Ethics, and Medicine (STREAM), Biomedical Ethics Unit, Department of Social Studies of Medicine, McGill University, H3A 1X1, Montreal, Canada jonathan.kimmelman@mcgill.ca.
Jonathan
J
Kimmelman
Studies of Translation, Ethics, and Medicine (STREAM), Biomedical Ethics Unit, Department of Social Studies of Medicine, McGill University, H3A 1X1, Montreal, Canada.
Benjamin
B
Carlisle
Studies of Translation, Ethics, and Medicine (STREAM), Biomedical Ethics Unit, Department of Social Studies of Medicine, McGill University, H3A 1X1, Montreal, Canada.
Georgina
G
Freeman
Centre for Practice Changing Research, Ottawa Hospital Research Institute, University of Ottawa, K1H 8L6, Ottawa, Canada.
Dean
D
Fergusson
D022126:Access to Information; D002986:Clinical Trials as Topic / Q000706:statistics & numerical data*; D017277:Drug Approval; D055808:Drug Discovery; D006801:Humans; D004364:Pharmaceutical Preparations; D011643:Publishing
D004364:Pharmaceutical Preparations