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J Clin Pharmacol. 2018 Jun;58(6):740-749. doi: 10.1002/jcph.1074. Epub 2018 Jan 25.

Is It Time for Going Beyond the P-Value Paradigm With the Estimation of the Probability of Clinical Benefit as a Criterion for Assessing the Outcomes of a Clinical Trial? A Case Study in Patients With Major Depressive Disorder.

Author information

1
R & D Department, Pharmacometrica, La Fouillade, France.
2
Psychiatry Department, Massachusetts General Hospital, Boston, MA, USA.

Abstract

The conventional statistical methodologies for evaluating treatment effect are based on hypothesis testing (P-value). Alternative measurements of treatment effect have been proposed for anti-infective treatments using the probability of target attainment. A general framework is proposed to extend this methodology to other therapeutic areas. A disease trial model is used for estimating the probability of reaching a treatment effect associated with relevant clinical benefits, in complement to the evaluation of the probability of rejecting the null hypothesis. A case study is presented in depression, where disease status is evaluated using bounded clinical scores (Hamilton Depression Rating Scale), and detectable treatment effect is inversely proportional to placebo response. The β-regression approach is used to model Hamilton scale scores, and a placebo-related criterion is proposed for determining the clinical benefit. The probability of reaching a clinical benefit represents a reliable criterion for replacing the P-value paradigm in the assessment of the outcomes of clinical trials.

KEYWORDS:

P-value; clinical benefit; placebo response; treatment effect; β-regression

PMID:
29372561
DOI:
10.1002/jcph.1074
[Indexed for MEDLINE]

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