Article Text
Abstract
Objectives To determine the relationship between manufacturer-related financial ties among investigators of published drug trials and rates of discrepant registered and published primary trial outcomes.
Design Cross-sectional study.
Setting Human subjects drug trials published in ‘core clinical’ MEDLINE journals in 2013.
Primary and secondary outcome measures The primary study endpoint was the presence of a prospectively registered, clearly defined primary outcome that matched the published primary outcome for each included trial. Secondary outcomes included assessments of registration timing and quality, and the impact of outcome discrepancies between registration and publication on the statistical significance of the included trials.
Results Of 192 included trials, 134 (70%) were positive and 58 (30%) were negative. Financial ties were present between first or last authors and drug manufacturers for 130 trials (68%), of which 78% were positive, versus 53% of trials with no financial ties that were positive. Clearly defined, prospectively registered outcomes that matched the published outcomes were present in just 76 of the 192 trials (40%). After adjusting for study start date and sample size, the observed relationship between investigator financial ties and the presence of a match between prospectively registered and published primary outcomes was of borderline statistical significance (OR 2.12, 95% CI 0.998 to 4.50). Studies with financial ties present were more likely than studies without ties to have been prospectively registered (78%vs48%, P<0.001) and were more likely to have prospectively registered a clearly defined primary outcome(62%vs35%, P<0.001).
Conclusions Less than half of the trials in this cohort were prospectively registered with a clear primary outcome that was consistent with the primary outcome reported in the published manuscript. The presence of investigator financial ties was associated with higher quality registration practices, though this association diminished after adjusting for factors that impact registration quality.
- conflict of interest
- clinicaltrials.gov
- trial registration
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Footnotes
Contributors CJ conceived the study. CJ, TFP-M and SK all contributed to the study design. CJ, BSM, AA, RA, AW and SS performed data collection. SK, DK and CJ verified the data. All authors analysed and interpreted the data. CJ drafted the manuscript and all authors critically revised the manuscript and read and approved the final manuscript.
Funding SK is funded by grants from the National Institutes of Health (RO1 HL116522-01A1 and RO1 HL114563-01A1) and Veterans Affairs Health Services Research and Development Service (1IP1HX001994). DK is funded by a Cancer Center Support Grant from the National Cancer Institute to Memorial Sloan Kettering Cancer Center (award number P30 CA008748).
Competing interests We have read and understood BMJ policy on declaration of interests and declare the following interests: CJ is an investigator on unrelated studies sponsored by AstraZeneca, Roche Diagnostics, Inc, Hologic, Inc, and Janssen, for which his department received research grants.
Patient consent Not required.
Provenance and peer review Not commissioned; externally peer reviewed.
Data sharing statement The full dataset is available from the corresponding author on reasonable request.