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

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 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 overestimate 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 the 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).

SUBMITTER: Michel MC

PROVIDER: S-EPMC8869609 | biostudies-literature | 2022 Jan

REPOSITORIES: biostudies-literature

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

Michel Martin C MC Staskin David D

Biomedicines 20220126 2

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 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 overestimate the probability of benefit at the single patient level based on outcome simulat ...[more]

PMID: 35203479

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Project description:BackgroundIn April 2005, researchers based at the Medical Research Council Clinical Trials Unit, set out to involve women affected by cervical cancer in a systematic review and meta-analysis of individual patient data to evaluate treatments for this disease. Each of the women had previously been treated for cervical cancer. Following completion of the meta-analysis, we aimed to evaluate the process of involvement from the researcher and research partner perspective.MethodsAn advisory group was first established to give advice on recruiting, supporting and involving women and led to efforts to recruit women to take part in the systematic review using different approaches. Evaluation of the process and outcomes of the partnership between the systematic reviewers and the patients, in respect to what the partnership achieved; what worked well and what were the difficulties; what was learned and the resource requirements, took place during the conduct of the meta-analysis and again after completion of the project.ResultsSix women, each of whom had received treatments for cervical cancer, were recruited as Patient Research Partners and five of these women subsequently took part in a variety of activities around the systematic review. They attended progress meetings and all but one attended a meeting at which the first results of the review were presented to all collaborators and gave feedback. Three of the women also became involved in a further related research project which led to an editorial publication from the patient perspective and also participated, along with two lead researchers, in the evaluation of the process and outcomes. While they were generally positive about the experience, one Patient Research Partner questioned the extent of the impact patients could make to the systematic review process.ConclusionsIn general, researchers and patient research partners felt that they had learned a lot from the process and considered it to have been a positive experience. The researchers felt that because of resource implications, patient involvement in future systematic reviews would probably have to be prioritized to those in which the greatest impacts could be achieved.

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

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

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