High-Value Cancer Care and the Problem With Surrogate Endpoints in the Quality/Cost Equation

Abstract

V alue in healthcare is defined as quality divided by cost. Value-based cancer care is the noble ideal that the correct cancer treatment can be recommended for each patient based on careful evaluation of treatment outcomes, patient experience, and cost. ASCO first formed the Task Force on the Cost of Cancer Care in 2007 with the laudable goal of making recommendations for how to balance highquality cancer care with the rising costs of treatment. From this task force, the ASCO Value Framework was launched as a physician-guided tool to facilitate open dialogue between physicians and patients in selecting high-value cancer treatment. 1 Shared decision-making is crucial in the modern era of cancer therapy, where proliferating options for disease management face off against ballooning treatment costs and increasing patient financial toxicity. Two versions of the ASCO Value Framework calculate net health benefit compared with cost for either advanced disease or potentially curative (adjuvant) clinical scenarios. Both incorporate clinical benefit and toxicity, with potential bonus points given for durable benefit ("tail of the curve") or quality of life improvements, among other clinical scenarios. Costs are reported as both drug acquisition costs and patient payment obligations to honor the financial burden on both health system and individual frameworks. In this issue of JNCCN, Cheng et al 2 analyze the incorporation of surrogate endpoints into the ASCO Value Framework clinical benefit score (CBS). This analysis is timely because surrogate endpoints are increasingly being used for both FDA approval 3 and in marketing new drugs-which are costly and may not have proven survival benefit-to physicians and patients. One evaluation of FDA-approved drugs based on the surrogate endpoint of response rate (RR) found that the benefit was quite small (,40% for about half of the drugs), and many drugs were granted accelerated approval based on single-arm studies with small sample sizes. 4 The ASCO Value Framework was designed to increase use of high-value care and foster discussion between physicians and patients; overestimated benefit based on surrogate endpoints may create false expectations and increase financial or physical toxicity without commensurate meaningful clinical gains. Surrogate endpoints are used to accelerate drug development because differences in overall survival (OS) often take longer to prove, which increases clinical trial costs and duration. 5 Previous research has shown that most surrogates in oncology had low or modest correlation with OS, suggesting that they should be used with caution when making treatment conclusions. 6 Despite this, surrogate endpoints are increasingly being used as the primary endpoint for oncology randomized controlled trials, 7 with growing concern from a contingent of oncologists that we've "put the cart before the horse" and may be placing patients at risk for little to no survival benefit. Cheng et al 2 evaluated the Value Framework CBS of 127 randomized controlled trials in adv...