Header

UZH-Logo

Maintenance Infos

P-hacking in clinical trials and how incentives shape the distribution of results across phases


Adda, Jérôme; Decker, Christian; Ottaviani, Marco (2020). P-hacking in clinical trials and how incentives shape the distribution of results across phases. Proceedings of the National Academy of Sciences of the United States of America, 117(24):13386-13392.

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<jats:italic>P</jats:italic>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.

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<jats:italic>P</jats:italic>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.

Statistics

Citations

Altmetrics

Downloads

7 downloads since deposited on 15 Feb 2021
7 downloads since 12 months
Detailed statistics

Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:03 Faculty of Economics > Department of Economics
Dewey Decimal Classification:330 Economics
Scopus Subject Areas:Health Sciences > Multidisciplinary
Uncontrolled Keywords:Multidisciplinary, clinical trials, drug development, selective reporting, p-hacking, economic incentives in research
Language:English
Date:16 June 2020
Deposited On:15 Feb 2021 10:39
Last Modified:16 Feb 2021 21:00
Publisher:National Academy of Sciences
ISSN:0027-8424
OA Status:Hybrid
Free access at:Publisher DOI. An embargo period may apply.
Publisher DOI:https://doi.org/10.1073/pnas.1919906117

Download

Hybrid Open Access

Download PDF  'P-hacking in clinical trials and how incentives shape the distribution of results across phases'.
Preview
Content: Published Version
Language: English
Filetype: PDF
Size: 1MB
View at publisher
Licence: Creative Commons: Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)
Download PDF  'P-hacking in clinical trials and how incentives shape the distribution of results across phases'.
Preview
Content: Accepted Version
Language: English
Filetype: PDF
Size: 1MB