Why So Many Significant Phase 3 Results in Clinical Trials?

Abstract

Planning and execution of clinical research and publication of results should conform to the highest ethical standards, given that human lives are at stake. However, economic incentives can generate conflicts of interest for investigators, who may be inclined to withhold unfavorable results or even tamper with the data. Analyzing p-values reported to the Clini-calTrials.gov registry with two different methodologies, we find suspicious patterns only for results from trials conducted by smaller industry sponsors, with presumably less reputation at stake. First, a density discontinuity test reveals an upward jump at the classical threshold for statistical significance for Phase 3 results by small industry sponsors, suggesting some selective reporting. Second, we find an excess mass of significant results in Phase 3 compared to Phase 2. However, we can explain almost completely this excess mass for large industry sponsors, once we account for the incentives to selectively continue research through a novel technique linking trials across phases. In contrast, for trials sponsored by small pharmaceutical companies, selective continuation of trials economizing on research costs only explains one third of the increase in the number of significant results from Phase 2 to Phase 3. The different pattern depending on the type of sponsor suggests that reputational concerns can mitigate the short-run economic incentives that undermine integrity in reporting results of clinical research.