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Review
. 2022 Oct;19(6):1844-1854.
doi: 10.1007/s13311-022-01284-x. Epub 2022 Aug 15.

Novel Clinical Trial Designs in Neuro-Oncology

Anurag Saraf  1   2 , Lorenzo Trippa  3 , Rifaquat Rahman  4
Affiliations
Review

Novel Clinical Trial Designs in Neuro-Oncology

Anurag Saraf et al. Neurotherapeutics. 2022 Oct.

Abstract

Scientific and technologic advances have led to a boon of candidate therapeutics for patients with malignancies of the central nervous system. The path from drug development to clinical use has generally followed a regimented order of sequential clinical trial phases. The recent increase in novel therapies, however, has strained the regulatory process and unearthed limitations of the current system, including significant cost, prolonged development time, and difficulties in testing therapies for rarer tumors. Novel clinical trial designs have emerged to increase efficiencies in clinical trial conduct to better evaluate and bring impactful drugs to patients in a timely manner. In order to better capture meaningful benefits for brain tumor patients, new endpoints to complement or replace traditional endpoints are also an increasingly important consideration. This review will explore the current challenges in the current clinical trial landscape and discuss novel clinical trial concepts, including consideration of limitations and risks of novel trial designs, within the context of neuro-oncology.

Keywords: Clinical trials; Modern clinical trials; Novel trial designs.

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Figures

Fig. 1
Fig. 1
Examples of master protocol trial designs, including basket trial, umbrella trial, and platform trials
Fig. 2
Fig. 2
Examples of clinical trial design, using a control arm, two experimental therapies (A, B) and a third experimental therapy (C) that is discovered after opening of trial. Traditional clinical trial can only investigate one experimental therapy (A) to a control arm at a time. Adaptive platform trials allow investigation of therapy A and B with a common control arm, and allow the addition of therapy C. Secondly, adaptive platform trials allow pre-specified interim analyses to close an ineffective therapy (B) early. Bayesian adaptive platform trials can allow biomarker-adjusted enrollment of each arm, allowing greater enrollment of patients with a specific “biomarker signature” as a trial progresses
See this image and copyright information in PMC

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