Progressive innovation in oncology: Valuing outcomes beyond survival

Abstract

Background: Breakthrough innovation in oncology is commonly considered to be a substantial increase in overall survival (OS) above specific thresholds. However, this growing emphasis on significant OS gain, undervalues new products and may not capture aspects of treatment that are important to patients, including quality of life (QoL), delayed progression or improvements in side-effect profiles. We argue that progressive innovation in clinical and non-clinical domains needs to be considered and valued in regulatory andhealth technology assessment (HTA) decisions.Methods: We conducted a targeted literature search for definitions of innovation in academic and gray literature, covering regulatory, HTA, and industry bodies. Current/proposed OS thresholds were applied to standard of care therapies in colorectal cancer (CRC) and non-small cell lung cancer (NSCLC) and assessed in the light of the actual HTA decision made. Results: Regulators andHTA agencies do not provide clear, consistent definitions of innovation, but absoluteOSgain consistently emerges askey frompolicy (e.g., England’s Cancer Drugs Fund) and clinical (e.g., American Society of Clinical Oncology [ASCO]) perspectives. The emphasis is increasingly on “clinically meaningful” change expressed as minimum thresholds: OS gain >2.5 months, HR >0.8; PFS gain >3 months, HR>0.5. OS thresholds published by the ASCOCommittee (Ellis et al., 2014) were applied toCRCandNSCLC.Onlyoneof sixCRCdrugs approved since 2000 met the threshold, but survival doubled in that time. Since 2005 no NSCLC products have met this OS threshold, yet survival for first-line patients with advanced disease increased twofold. Conclusions: Innovation should be judged in relation to the value provided to patients and health systems, not restricted to one-time large survival gains. Smaller sequential clinical gains and improved QoL, safety, convenience, and system efficiency should be considered in assessing value and innovation. Progressive innovation provides opportunities for immediate benefit, including survival until the next therapy is available, and uncovering new clinical pathways with significant cumulative benefit over time. Recognition of this “option value” for future health and research advances is needed. Regulatory and HTA agencies should balance clinical and economic gains, and societal and patient preferences when evaluating innovation in a new therapy.