Improving Clinical Trial Efficiency

Thinking outside the Box

Sumithra J Mandrekar, Suzanne E. Dahlberg, Richard Simon

Research output: Contribution to journalReview article

35 Citations (Scopus)

Abstract

Clinical trial design strategies have evolved over the past few years as a means to accelerate the drug development process so that the right therapies can be delivered to the right patients. Basket, umbrella, and adaptive enrichment strategies represent a class of novel designs for testing targeted therapeutics in oncology. Umbrella trials include a central infrastructure for screening and identification of patients, and focus on a single tumor type or histology with multiple subtrials, each testing a targeted therapy within a molecularly defined subset. Basket trial designs offer the possibility to include multiple molecularly defined subpopulations, often across histology or tumor types, but included in one cohesive design to evaluate the targeted therapy in question. Adaptive enrichment designs offer the potential to enrich for patients with a particular molecular feature that is predictive of benefit for the test treatment based on accumulating evidence from the trial. This review will aim to discuss the fundamentals of these design strategies, the underlying statistical framework, the logistical barriers of implementation, and, ultimately, the interpretation of the trial results. New statistical approaches, extensive multidisciplinary collaboration, and state of the art data capture technologies are needed to implement these strategies in practice. Logistical challenges to implementation arising from centralized assay testing, requirement of multiple specimens, multidisciplinary collaboration, and infrastructure requirements will also be discussed. This review will present these concepts in the context of the National Cancer Institute's precision medicine initiative trials: MATCH, ALCHEMIST, Lung MAP, as well as other trials such as FOCUS4.

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Clinical Trials
Histology
Therapeutics
Precision Medicine
National Cancer Institute (U.S.)
Patient Rights
Neoplasms
Technology
Lung
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Improving Clinical Trial Efficiency : Thinking outside the Box. / Mandrekar, Sumithra J; Dahlberg, Suzanne E.; Simon, Richard.

In: American Society of Clinical Oncology educational book. American Society of Clinical Oncology. Meeting, 2015, p. e141-e147.

Research output: Contribution to journalReview article

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