Preprint Review Version 1 Preserved in Portico This version is not peer-reviewed

Study Designs for Evaluation of Combination Treatment: Focus On Individual Patient Benefit

Version 1 : Received: 2 January 2022 / Approved: 6 January 2022 / Online: 6 January 2022 (10:14:10 CET)

A peer-reviewed article of this Preprint also exists.

Michel, M.C.; Staskin, D. Study Designs for Evaluation of Combination Treatment: Focus on Individual Patient Benefit. Biomedicines 2022, 10, 270. Michel, M.C.; Staskin, D. Study Designs for Evaluation of Combination Treatment: Focus on Individual Patient Benefit. Biomedicines 2022, 10, 270.

Abstract

Combination treatment, i.e., the use of two or more drugs for the same condition, is frequent in medicine if monotherapy yields an insufficient therapeutic response. We here review and challenge clinical study designs and formats of reporting outcomes for the evaluation of the benefit/risk ratio of combination treatment over monotherapy. We demonstrate that benefits of combination treatment at the group level over-estimate the probability of benefit at the single patient level based on outcome simulations under almost any imaginable setting. Based on these findings we propose that studies testing combination treatment should always report on percentages of responders to monotherapy and combination treatment. We provide equations that allow calculation of the percentage of patients truly benefitting from combination (responders to both monotherapies) and that of patients exposed to risk of harm from adverse effects without a reasonable expectation of individual benefit. These considerations are explained based on real clinical data, mostly from the field of functional urology (male lower urinary tract symptoms).

Keywords

combination treatment; monotherapy; clinical trial design; benefit/risk assessment

Subject

Medicine and Pharmacology, Pharmacology and Toxicology

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