National Cancer Institute Basket/Umbrella Clinical Trials: MATCH, LungMAP, and Beyond.
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ABSTRACT:
SUBMITTER: Chen AP
PROVIDER: S-EPMC6658131 | biostudies-literature | 2019 Jul/Aug
REPOSITORIES: biostudies-literature
Publications
National Cancer Institute Basket/Umbrella Clinical Trials: MATCH, LungMAP, and Beyond.
Chen Alice P AP Eljanne Mariam M Harris Lyndsay L Malik Shakuntala S Seibel Nita L NL
Cancer journal (Sudbury, Mass.) 20190701 4
With advances in genetic testing and its common usage, the field of precision medicine has exploded in the field of oncology. The National Cancer Institute is uniquely positioned to lead in this area of research through its wide network of investigators, partnerships with pharmaceutical companies in drug development, and laboratory capabilities. It has developed a portfolio of trials as part of a Precision Medicine Initiative that uses various basket/umbrella designs to increase the understandin ...[more]
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Project description:ObjectivesAmid a rapid increase in cancer care costs, we examined the extent to which economic evaluations (EEs) were conducted for new treatments evaluated in clinical trials at SWOG, a large National Cancer Institute-sponsored cancer research network.MethodsWe investigated phase III cancer treatment clinical trials activated from 1980 onward with primary articles reporting the protocol-designated endpoints published in scientific journals by 2017. Using PubMed, Web of Science, and EconLit, we searched for EEs using trial name, cancer type, information on the comparison arms, and refined keywords for EE designs. We reported the overall proportion of trials with associated EEs and trends of this proportion over time. We synthesized and analyzed information on funding sources, health outcomes, and sources of quality-of-life and cost data from the EEs.ResultsAmong 182 examined trials, 15 EEs were associated with 13 (7.1%) trials. Among the EEs, almost half (7 of 15) were either unfunded or did not report funding information, whereas nearly half (7 of 15) were funded by pharmaceutical companies and 2 (2 of 15, 13.3%) were supported by federal funding. All EEs reported a healthcare payer perspective. The proportion of trials with an associated EE increased from 1980 to 1989 and 2000 to 2009, but never exceeded 11%. Sources for cost and quality-of-life data for the EEs primarily came from outside the clinical trials.ConclusionsFew economic studies of treatments evaluated in National Cancer Institute-sponsored clinical trials have been conducted. Policymakers, payers, and patients lack economic evidence to consider newly evaluated cancer treatments, despite an urgent need to control healthcare costs.
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Project description:BACKGROUND:Novel precision oncology trial designs, such as basket and umbrella trials, are designed to test new anticancer agents in more effective and affordable ways. However, they present some ethical concerns referred to scientific validity, risk-benefit balance and informed consent. Our aim is to discuss these issues in basket and umbrella trials, giving examples of two ongoing cancer trials: NCI-MATCH (National Cancer Institute - Molecular Analysis for Therapy Choice) and Lung-MAP (Lung Cancer Master Protocol) study. MAIN BODY:We discuss three ethical requirements for clinical trials which may be challenged in basket and umbrella trial designs. Firstly, we consider scientific validity. Thanks to the new trial designs, patients with rare malignancies have the opportunity to be enrolled and benefit from the trial, but due to insufficient accrual, the trial may generate clinically insignificant findings. Inadequate sample size in study arms and the use of surrogate endpoints may result in a drug approval without confirmed efficacy. Moreover, complexity, limited quality and availability of tumor samples may not only introduce bias and result in unreliable and unrepresentative findings, but also can potentially harm patients and assign them to an inappropriate therapy arm. Secondly, we refer to benefits and risks. Novel clinical trials can gain important knowledge on the variety of tumors, which can be used in future trials to develop effective therapies. However, they offer limited direct benefits to patients. All potential participants must wait about 2 weeks for the results of the genetic screening, which may be stressful and produce anxiety. The enrollment of patients whose tumors harbor multiple mutations in treatments matching a single mutation may be controversial. As to informed consent - the third requirement we discuss, the excessive use of phrases like "personalized medicine", "tailored therapy" or "precision oncology" might be misleading and cause personal convictions that the study protocol is designed to fulfill the individual health-related needs of participants. CONCLUSIONS:We suggest that further approaches should be implemented to enhance scientific validity, reduce misunderstandings and risks, thus maximizing the benefits to society and to trial participants.
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