DEPERROR: Risks of systematic errors in drug and non-drug randomized clinical trials assessing intervention effects in patients with unipolar depression

BACKGROUND: Systematic errors in randomized clinical trials (RCTs) overestimate treatment effects. We systematically assessed the risks of bias in RCTs assessing the effects of drug and non-drug interventions for patients with unipolar depression.

METHODS: We searched bibliographic databases for drug and non-drug RCTs including patients with depression. We assessed the following risk of bias domains: sequence generation, allocation concealment, baseline imbalance, blinding, intention-to-treat analysis, selective outcome reporting, and funding. Risks of bias were compared for drug and non-drug trials and according to year of publication (before 1990; from 1990 to 1999; and 2000 to 2010).

RESULTS: Comparing drug trials (N=775) to non-drug trials (N=73), the proportion of drug trials with low risk of bias seemed superior regarding blinding of participants (p<0.001), blinding of health-care providers (p<0.001), and blinded outcome assessment (p<0.001). Non-drug trials were superior regarding sequence generation (p<0.001), allocation concealment (p=0.002), intention-to-treat analysis (p<0.001), and baseline imbalance (p=0.006). Adequate blinding of data managers (p=0.45), blinding of statisticians (p=0.69), and selective outcome reporting (p=0.55) did not differ. 41.5% of drug trials were funded by for-profit organizations compared to 12.3% of non-drug trials (p<0.001). In drug trials, the risk of bias decreased significantly over time. This did not reach statistical significance in non-drug trials.

LIMITATIONS: This study only included trials published before 2010.

CONCLUSIONS: Included trials were associated with high risks of bias which may distort effect estimates. The risks of bias decreased with time for drug trials.