Laurence S Freedman1. 1. Gertner Institute for Epidemiology and Health Policy Research, Tel Hashomer 52161, Israel. lsf@actcom.co.il
Abstract
BACKGROUND: When applying classical tests of the null hypothesis in clinical trials, there has been considerable controversy over the choice between a one-sided versus a two-sided test. The choice between a one-sided and two-sided test still impacts on sample size calculations, assessment of study results by regulatory authorities, and publication of study results in academic journals. PURPOSE: To analyze the main elements in the controversy, and examine the procedures from both a Bayesian and classical viewpoint. METHODS AND RESULTS: Using a Bayesian decision framework, it is shown that there is no reason to double the p-value when moving from a one-sided to a two-sided test. Within the classical framework, it is shown that the doubling of the p-value results from a discontinuity due to testing a point null hypothesis. A three-decision rule, credited to Neyman or Wald, is presented that does not require the doubling of the p-value, and is consistent with a Bayesian approach. CONCLUSIONS: For most comparative clinical trials the three-decision rule is appropriate, and its use would abolish the controversy over one-sided tests.
BACKGROUND: When applying classical tests of the null hypothesis in clinical trials, there has been considerable controversy over the choice between a one-sided versus a two-sided test. The choice between a one-sided and two-sided test still impacts on sample size calculations, assessment of study results by regulatory authorities, and publication of study results in academic journals. PURPOSE: To analyze the main elements in the controversy, and examine the procedures from both a Bayesian and classical viewpoint. METHODS AND RESULTS: Using a Bayesian decision framework, it is shown that there is no reason to double the p-value when moving from a one-sided to a two-sided test. Within the classical framework, it is shown that the doubling of the p-value results from a discontinuity due to testing a point null hypothesis. A three-decision rule, credited to Neyman or Wald, is presented that does not require the doubling of the p-value, and is consistent with a Bayesian approach. CONCLUSIONS: For most comparative clinical trials the three-decision rule is appropriate, and its use would abolish the controversy over one-sided tests.
Authors: Francis Kim; Charles Maynard; Cameron Dezfulian; Michael Sayre; Peter Kudenchuk; Thomas Rea; Deborah Sampson; Michele Olsufka; Susanne May; Graham Nichol Journal: JAMA Date: 2021-01-12 Impact factor: 157.335
Authors: Jonathan M Dreyfuss; Yixing Yuchi; Xuehong Dong; Vissarion Efthymiou; Hui Pan; Donald C Simonson; Ashley Vernon; Florencia Halperin; Pratik Aryal; Anish Konkar; Yinong Sebastian; Brandon W Higgs; Joseph Grimsby; Cristina M Rondinone; Simon Kasif; Barbara B Kahn; Kathleen Foster; Randy Seeley; Allison Goldfine; Vera Djordjilović; Mary Elizabeth Patti Journal: Nat Commun Date: 2021-11-29 Impact factor: 17.694