Precision medicine needs randomized clinical trials

ABSTRACT The advent of precision medicine has prompted profound changes in clinical cancer research, and the rising numbers of new therapeutic agents pose challenges in terms of the most

appropriate trial designs and effects on the drug-approval process. In the past 5 years, some remarkably efficacious drugs have been approved based on evidence from uncontrolled phase I

trials. We challenge the view that the expected benefits from new drugs are generally sufficient to forgo a randomized trial with patients assigned to a control arm (a regimen other than the

experimental treatment). Relying on efficacy results from uncontrolled clinical trials can result in expedited drug approval, but the disadvantages of this practice must be taken into

account. For example, the apparent improvements in outcomes observed in an early single-arm trial of a new therapy might reflect the prognostic nature of the target, rather than a true

treatment effect. Moreover, the predictive role of biomarkers cannot be definitively ascertained without randomly assigning patients to a control arm. We discuss the need for such

randomization to a true control in all phases of drug development and the role of companion biomarker testing. We propose that an increased use of randomization will facilitate a seamless

transition between phases of drug and/or biomarker development. Access through your institution Buy or subscribe This is a preview of subscription content, access via your institution ACCESS

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FAQs * Contact customer support SIMILAR CONTENT BEING VIEWED BY OTHERS CHALLENGES AND OPPORTUNITIES ASSOCIATED WITH THE MD ANDERSON IMPACT2 RANDOMIZED STUDY IN PRECISION ONCOLOGY Article

Open access 27 October 2022 RANDOMISED PHASE 1 CLINICAL TRIALS IN ONCOLOGY Article 10 June 2021 PRECISION MEDICINE: AFFORDING THE SUCCESSES OF SCIENCE Article Open access 04 January 2023

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ACKNOWLEDGEMENTS We thank the three reviewers who anonymously contributed to our paper with their insightful and constructive critique. AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * Everardo

D. Saad is at the International Drug Development Institute (IDDI), Avenue Provinciale 30, 1340 Ottignies-Louvain-la-Neuve, Belgium., Everardo D. Saad * Xavier Paoletti is at the Institut

Gustave Roussy, 114 Rue Edouard Vaillant, 94800 Villejuif, France., Xavier Paoletti * Tomasz Burzykowski is at the IDDI, Avenue Provinciale 30, 1340 Ottignies-Louvain-la-Neuve, Belgium,

Tomasz Burzykowski * at the Interuniversity Institute for Biostatistics and Statistical Bioinformatics (I-BioStat), Hasselt University, Martelarenlaan 42, 3500 Hasselt, Belgium., Tomasz

Burzykowski * Marc Buyse is at the I-BioStat, Hasselt University, Martelarenlaan 42, 3500 Hasselt, Belgium, Marc Buyse * at the IDDI, 185 Alewife Brook Parkway, Suite 410, Cambridge,

Massachusetts 02138, USA., Marc Buyse Authors * Everardo D. Saad View author publications You can also search for this author inPubMed Google Scholar * Xavier Paoletti View author

publications You can also search for this author inPubMed Google Scholar * Tomasz Burzykowski View author publications You can also search for this author inPubMed Google Scholar * Marc

Buyse View author publications You can also search for this author inPubMed Google Scholar CONTRIBUTIONS All authors researched data for the article and contributed to discussions of the

article's content. E.D.S. and M.B. wrote, reviewed, and edited the manuscript before submission. CORRESPONDING AUTHOR Correspondence to Everardo D. Saad. ETHICS DECLARATIONS COMPETING

INTERESTS The authors declare no competing financial interests. POWERPOINT SLIDES POWERPOINT SLIDE FOR FIG. 1 POWERPOINT SLIDE FOR TABLE 1 RIGHTS AND PERMISSIONS Reprints and permissions

ABOUT THIS ARTICLE CITE THIS ARTICLE Saad, E., Paoletti, X., Burzykowski, T. _et al._ Precision medicine needs randomized clinical trials. _Nat Rev Clin Oncol_ 14, 317–323 (2017).

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