Clinical Trial Registration — Looking Back and Moving Ahead

Lainé, Christine; Horton, Richard; Cd, DeAngelis; Drazen, Jeffrey M.; Fa, Frizelle; Godlee, Fiona; Haug, Charlotte; Pc, Hébert; Kotzin, Sheldon; Marušić, Ana; Sahni, Peush; Schroeder, Torben V.; Hc, Sox; Mb, Van Der Weyden; Fw, Verheugt

doi:10.1056/nejme078110

Cited by 235 publications

(64 citation statements)

References 2 publications

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“…Finally, the International Committee of Medical Journal Editors (ICMJE) could create policies that mandate the reporting of results, perhaps concurrent with peer-reviewed publication or FDA approval, since earlier ICMJE policies have notably improved rates of trial registration before publication. 25 Other factors that could prompt increased reporting to CinicalTrials.gov include notification by the National Library of Medicine to sponsors regarding the status of all applicable clinical trials and reporting deadlines, development of internal reporting policies by sponsors, endorsement of requirements for the reporting of results by federal and nonfederal funding agencies, and enforcement of legal penalties.…”

Section: Discussionmentioning

confidence: 99%

Compliance with Results Reporting at ClinicalTrials.gov

et al. 2015

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BACKGROUND The Food and Drug Administration Amendments Act (FDAAA) mandates timely reporting of results of applicable clinical trials to ClinicalTrials.gov. We characterized the proportion of applicable clinical trials with publicly available results and determined independent factors associated with the reporting of results. METHODS Using an algorithm based on input from the National Library of Medicine, we identified trials that were likely to be subject to FDAAA provisions (highly likely applicable clinical trials, or HLACTs) from 2008 through 2013. We determined the proportion of HLACTs that reported results within the 12-month interval mandated by the FDAAA or at any time during the 5-year study period. We used regression models to examine characteristics associated with reporting at 12 months and throughout the 5-year study period. RESULTS From all the trials at ClinicalTrials.gov, we identified 13,327 HLACTs that were terminated or completed from January 1, 2008, through August 31, 2012. Of these trials, 77.4% were classified as drug trials. A total of 36.9% of the trials were phase 2 studies, and 23.4% were phase 3 studies; 65.6% were funded by industry. Only 13.4% of trials reported summary results within 12 months after trial completion, whereas 38.3% reported results at any time up to September 27, 2013. Timely reporting was independently associated with factors such as FDA oversight, a later trial phase, and industry funding. A sample review suggested that 45% of industry-funded trials were not required to report results, as compared with 6% of trials funded by the National Institutes of Health (NIH) and 9% of trials that were funded by other government or academic institutions. CONCLUSIONS Despite ethical and legal obligations to disclose findings promptly, most HLACTs did not report results to ClinicalTrials.gov in a timely fashion during the study period. Industry-funded trials adhered to legal obligations more often than did trials funded by the NIH or other government or academic institutions.

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Section: Discussionmentioning

confidence: 99%

Compliance with Results Reporting at ClinicalTrials.gov

et al. 2015

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“…Since 2005, the International Committee of Medical Journal Editors (ICMJE), on behalf of its participating journals, has required prospective registration of all clinical trials 28 ; this move was designed in part to limit publication bias that may have led to a lower likelihood of publication of negative studies in which industry collaborated or simply funded, and has been broadly supported. 29,30 Although trial registration remains incomplete 31 and its impact on publication of negative trials has been disappointing, 32 among the more recent publications we evaluated the ICMJE policy may be blunting the previously documented effect of industry collaboration on positive results. Our negative finding may also relate to other changes regarding author transparency.…”

Section: Discussionmentioning

confidence: 99%

Impact of industry collaboration on randomised controlled trials in oncology

Linker

Yang

Roper

et al. 2017

European Journal of Cancer

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Background Industry funders can simply provide money or collaborate in trial design, analysis, or reporting of clinical trials. Our aim was to assess the impact of industry collaboration on trial methodology and results of randomized controlled trials (RCT). Methods We searched PubMed for oncology RCTs published May 2013 to December 2015 in peer-reviewed journals with impact factor > 5 requiring reporting of funder role. Two authors extracted methodologic (primary endpoint; blinding of the patient, clinician, and outcomes assessor; and analysis) and outcome data. We used descriptive statistics and two-sided Fisher exact tests to compare characteristics of trials with collaboration, with industry funding only, and without industry funding. Results We included 224 trials. Compared to those without industry funding, trials with collaboration used more placebo control (RR 3·59, 95% CI [1·88–6·83], p<·0001), intention-to-treat analysis (RR 1·32, 95% CI [1·04–1·67], p=·02), and blinding of patients (RR 3·05, 95% CI [1·71–5·44], p<·0001), clinicians (RR 3·36, 95% CI [1·83–6·16], p=<·001), and outcomes assessors (RR 3·03, 95% CI [1·57–5·83], p=·0002). They did not differ in use of overall survival as a primary endpoint (RR 1·27 95% CI [0·72–2·24]) and were similarly likely to report positive results (RR 1·11 95% CI [0·85–1·46], p=0·45). Studies with funding only did not differ from those without funding. Conclusions Oncology RCTs with industry collaboration were more likely to use some high-quality methods than those without industry funding, with similar rates of positive results. Our findings suggest that collaboration is not associated with trial outcomes and that mandatory disclosure of funder roles may mitigate bias.

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“…10,11 In 1997, U.S. law mandated the registration of trials of investigational new drugs for serious or life-threatening diseases, 12 resulting in the February 2000 implementation of ClinicalTrials.gov, a publicly accessible online database operated by the National Library of Medicine at the NIH. 13 This law was followed by other international efforts, such as the policy of the International Committee of Medical Journal Editors (ICMJE), 10 that helped increase trial registrations (Fig. 1).…”

Section: Introductionmentioning

confidence: 99%