Sharing some interim data in trial monitoring can mislead or unmask trial investigators: A scenario-based survey of trial experts.

ABSTRACT:

Background

Sharing masked interim results by the Data Safety Monitoring Board (DSMB) with non-DSMB members is an important issue that can affect trial integrity. Our survey's objective is to collect evidence to understand how seemingly masked interim results or result extrapolations are interpreted and discuss whether these results should be shared at interim.

Methods

Conducted a 6 scenario-question survey asking trial experts how they interpreted three kinds of seemingly masked interim results or result extrapolation measures (interim combined event rate, adaptive conditional power and "unconditional" conditional power).

Results

Thirty-one current Consolidated Standards of Reporting Trials group affiliates were invited for survey participation (February 2015). Response rate: 71.0% (22/31). About half, 52.6% (95% CI: 28.9%-74.0%), (10/19), correctly indicated that the interim combined event rate can be interpreted in three ways (drug X doing better than placebo, worse than placebo or the same) if shared at interim. The majority, 72.2% (95% CI: 46.5%-89.7%), (13/18), correctly indicated that the adaptive conditional power suggests relative treatment group effects. The majority, 53.3% (95% CI: 26.6%-77.0%), (8/15), incorrectly indicated that the "unconditional" conditional power suggests relative treatment group effects.

Discussion/conclusion

Knowledge of these three results or result extrapolation measures should not be shared outside of the DSMB at interim as they may mislead or unmask interim results, potentially introducing trial bias. For example, the interim combined event rate can be interpreted in one of three ways potentially leading to mistaken guesswork about interim results. Knowledge of the adaptive conditional power by non-DSMB members is telling of relative treatment effects thus unmasking of interim results.

SUBMITTER: Borg Debono V 

PROVIDER: S-EPMC5898486 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature