Working Paper: CEPR ID: DP13836
Authors: Jerome Adda; Christian Decker; Marco Ottaviani
Abstract: Clinical research should conform to high standards of ethical and scientific integrity, 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 data in order to achieve desired outcomes. To shed light on the integrity of clinical trial results, this paper systematically analyzes the distribution of p-values of primary outcomes for phase II and phase III drug trials reported to the ClinicalTrials.gov registry. First, we detect no bunching of results just above the classical 5% threshold for statistical significance. Second, a density discontinuity test reveals an upward jump at the 5% threshold for phase III results by small industry sponsors. Third, we document a larger fraction of significant results in phase III compared to phase II. Linking trials across phases, we find that early favorable results increase the likelihood of continuing into the next phase. Once we take into account this selective continuation, we can explain almost completely the excess of significant results in phase III for trials conducted by large industry sponsors. For small industry sponsors, instead, part of the excess remains unexplained.
Keywords: clinical trials; drug development; selective reporting; phacking; economic incentives in research
JEL Codes: D8; O3
Edges that are evidenced by causal inference methods are in orange, and the rest are in light blue.
| Cause | Effect |
|---|---|
| economic incentives (M52) | integrity of reported trial outcomes (C90) |
| phase II outcomes (I12) | phase III participation (P30) |
| larger industry sponsors (L83) | selective continuation behavior (D91) |
| phase III trials sponsored by small firms (L26) | selective reporting behavior (D91) |
| observed differences in significant results between phases II and III (C90) | selective continuation (C34) |
| early favorable results in phase II trials (L65) | likelihood of continuation into phase III trials (C41) |
| selective continuation (C34) | excess of significant results in phase III (C52) |