Financial ties of principal investigators and randomized controlled trial outcomes: cross sectional study
BMJ 2017; 356 doi: https://doi.org/10.1136/bmj.i6770 (Published 17 January 2017) Cite this as: BMJ 2017;356:i6770
- Rosa Ahn, medical student1,
- Alexandra Woodbridge, research assistant2,
- Ann Abraham, research assistant2,
- Susan Saba, research professional3,
- Deborah Korenstein, director of clinical effectiveness4,
- Erin Madden, staff statistician2,
- W John Boscardin, professor of biostatistics and epidemiology2 5,
- Salomeh Keyhani, associate professor of general internal medicine2 5
- 1Oregon Health and Science University, Portland, OR 97239, USA
- 2San Francisco VA Medical Center, San Francisco, CA 94121, USA
- 3Stanford University School of Medicine, Palo Alto, CA 94304, USA
- 4Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
- 5University of California, San Francisco, San Francisco, CA 94121, USA
- Correspondence to: S Keyhani salomeh.keyhani{at}ucsf.edu
- Accepted 6 December 2016
Abstract
Objective To examine the association between the presence of individual principal investigators’ financial ties to the manufacturer of the study drug and the trial’s outcomes after accounting for source of research funding.
Design Cross sectional study of randomized controlled trials (RCTs).
Setting Studies published in “core clinical” journals, as identified by Medline, between 1 January 2013 and 31 December 2013.
Participants Random sample of RCTs focused on drug efficacy.
Main outcome measure Association between financial ties of principal investigators and study outcome.
Results A total of 190 papers describing 195 studies met inclusion criteria. Financial ties between principal investigators and the pharmaceutical industry were present in 132 (67.7%) studies. Of 397 principal investigators, 231 (58%) had financial ties and 166 (42%) did not. Of all principal investigators, 156 (39%) reported advisor/consultancy payments, 81 (20%) reported speakers’ fees, 81 (20%) reported unspecified financial ties, 52 (13%) reported honorariums, 52 (13%) reported employee relationships, 52 (13%) reported travel fees, 41 (10%) reported stock ownership, and 20 (5%) reported having a patent related to the study drug. The prevalence of financial ties of principal investigators was 76% (103/136) among positive studies and 49% (29/59) among negative studies. In unadjusted analyses, the presence of a financial tie was associated with a positive study outcome (odds ratio 3.23, 95% confidence interval 1.7 to 6.1). In the primary multivariate analysis, a financial tie was significantly associated with positive RCT outcome after adjustment for the study funding source (odds ratio 3.57 (1.7 to 7.7). The secondary analysis controlled for additional RCT characteristics such as study phase, sample size, country of first authors, specialty, trial registration, study design, type of analysis, comparator, and outcome measure. These characteristics did not appreciably affect the relation between financial ties and study outcomes (odds ratio 3.37, 1.4 to 7.9).
Conclusions Financial ties of principal investigators were independently associated with positive clinical trial results. These findings may be suggestive of bias in the evidence base.
Footnotes
Contributors: SK had the idea for the study. SK, DK, RA, AW, AA, and SS created the study design. RA, AW, AA, and SS collected the data. SK and DK verified the data. EM, WJB, SK, RA, AW, AA, SS, and DK analyzed and interpreted the data. RA, AW, AA, SS, SK, DK, EM, and WJB wrote and revised the manuscript. All authors critically revised the manuscript and approved the final version for submission. RA, AW, AA, and SS contributed equally to the work and are considered co-first authors. SK is the guarantor.
Funding: This project was not directly supported by any research funds. SK is funded by grants from the National Institutes of Health (RO1 HL116522-01A1, RO1 HL114563-01A1) and Veterans Affairs Health Services Research and Development Service (1IP1HX001994). DK’s work on this paper was supported by a Cancer Center Support Grant from the National Cancer Institute to Memorial Sloan Kettering Cancer Center (award number P30 CA008748).
Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf (available on request from the corresponding author) and declare: no support from any organization for the submitted work, other than that described above; no financial relationships with any organizations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work.
Ethical approval: Not needed.
Data sharing: Dataset available from corresponding author on request.
Transparency: The lead author (the manuscript’s 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 (and, if relevant, registered) have been explained.
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