Uncertain use of a fixed p value significance threshold in randomized clinical trials

The continued use of a fixed p value significance threshold, such as p < 0.05, in randomized clinical trials has long been debated. Although such thresholds are conventional, they may not always align with the ethical principle of beneficence, which emphasizes minimizing harm and maximizing benefit. Reliance on a single, fixed α level increases the risk of both false-positive (type I) and false-negative (type II) error rates, thereby either exposing patients to ineffective or harmful treatments or withholding beneficial therapies. While lowering the threshold to values like 0.005 may reduce the false-positive rate, it also increases the false-negative rate and does not resolve the reproducibility crisis. Similar to diagnostic testing, the selection of a significance threshold should be context-dependent, influenced by study design, sample size, prior evidence, and effect size, among other things. Employing a flexible α level that balances type I and type II errors may enhance both scientific validity and ethical integrity. Thus, rigid adherence to fixed α levels, no matter how stringent, may be methodologically limiting and ethically questionable.

Authors

Institutions

Publication Details

Journal
Trials
Published
2026-01-07
DOI
https://doi.org/10.1186/s13063-026-09438-4
Primary Topic
Meta-analysis and systematic reviews
Type
article
Field-Weighted Citation Impact
0.00
Controls
|||
ALL TIME
JAN
FEB
MAR
APR
MAY
JUN
JUL
AUG
SEP
OCT
article

Uncertain use of a fixed p value significance threshold in randomized clinical trials

Farrokh Habibzadeh
Trials
Meta-analysis and systematic reviews
article

Uncertain use of a fixed p value significance threshold in randomized clinical trials

Farrokh Habibzadeh
article en

Abstract

The continued use of a fixed p value significance threshold, such as p < 0.05, in randomized clinical trials has long been debated. Although such thresholds are conventional, they may not always align with the ethical principle of beneficence, which emphasizes minimizing harm and maximizing benefit. Reliance on a single, fixed α level increases the risk of both false-positive (type I) and false-negative (type II) error rates, thereby either exposing patients to ineffective or harmful treatments or withholding beneficial therapies. While lowering the threshold to values like 0.005 may reduce the false-positive rate, it also increases the false-negative rate and does not resolve the reproducibility crisis. Similar to diagnostic testing, the selection of a significance threshold should be context-dependent, influenced by study design, sample size, prior evidence, and effect size, among other things. Employing a flexible α level that balances type I and type II errors may enhance both scientific validity and ethical integrity. Thus, rigid adherence to fixed α levels, no matter how stringent, may be methodologically limiting and ethically questionable.

TrialsVol. 27(1)
Hafez Hospital (IR)
Gender equality
Openalex Percentile: Top 96%
Meta-analysis and systematic reviews
AI Navigator

Ask Laika to Summarize, Analyze, and Connect papers live on the map.

Summarize Papers & Methodologies

Extract key findings, datasets, and comparative methods across publications.

Benchmark Rankings & Visual Analytics

Rank top research institutions, authors, funders, topics, and journals by Field-Weighted Citation Impact (FWCI) and paper volume with instant charts.

Connect Distant Disciplines

Bridge topological clusters on the map to find hidden collaborative intersections.