Primary outcome switching among drug trials with and without principal investigator financial ties to industry: a cross-sectional study.

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.