Natalia R Kunst1, Fernando Alarid-Escudero2, A David Paltiel3, Shi-Yi Wang4. 1. Department of Health Management and Health Economics, University of Oslo, Oslo, Norway; Department of Internal Medicine, Yale University School of Medicine, New Haven, CT, USA; Department of Epidemiology and Biostatistics, Amsterdam UMC, Amsterdam, the Netherlands; LINK Medical Research, Oslo, Norway. Electronic address: n.r.kunst@medisin.uio.no. 2. Drug Policy Program, Center for Research and Teaching in Economics (CIDE), Aguascalientes, Mexico; National Council on Science and Technology (CONACyT), Mexico City, Mexico. 3. Department of Health Policy and Management, Yale School of Public Health, New Haven, CT, USA. 4. Department of Chronic Disease Epidemiology, Yale University School of Public Health, New Haven, CT, USA; Cancer Outcomes, Public Policy, and Effectiveness Research Center, Yale Cancer Center and Yale University School of Medicine, New Haven, CT, USA.
Abstract
OBJECTIVES: The 21-gene assay Oncotype DX (21-GA) shows promise as a guide in deciding when to initiate adjuvant chemotherapy in women with hormone receptor-positive early-stage breast cancer. Nevertheless, its routine use remains controversial, owing to insufficient evidence of its clinical utility and cost-effectiveness. Accordingly, we aim to quantify the value of conducting further research to reduce decision uncertainty in the use of the 21-GA. METHODS: Using value of information methods, we first generated probability distributions of survival and costs for decision making with and without the 21-GA alongside traditional risk prediction. These served as the input to a comparison of 3 alternative study designs: a retrospective observational study to update risk classification from the 21-GA, a prospective observational study to estimate prevalence of chemotherapy use, and a randomized controlled trial (RCT) of the 21-GA predictive value. RESULTS: We found that current evidence strongly supports the use of the 21-GA in intermediate- and high-risk women. Further research should focus on low-risk women, among whom the cost-effectiveness findings remained equivocal. For this population, we identified a high value of reducing uncertainty in the 21-GA use for all proposed research studies. The RCT had the greatest potential to efficiently reduce the likelihood of choosing a suboptimal strategy, providing a value between $162 million and $1.1 billion at willingness-to-pay thresholds of $150 000 to $200 000/quality-adjusted life years. CONCLUSION: Future research to inform 21-GA decision making is of high value. The RCT of the 21-GA predictive value has the greatest potential to efficiently reduce decision uncertainty around 21-GA use in women with low-risk early-stage breast cancer.
OBJECTIVES: The 21-gene assay Oncotype DX (21-GA) shows promise as a guide in deciding when to initiate adjuvant chemotherapy in women with hormone receptor-positive early-stage breast cancer. Nevertheless, its routine use remains controversial, owing to insufficient evidence of its clinical utility and cost-effectiveness. Accordingly, we aim to quantify the value of conducting further research to reduce decision uncertainty in the use of the 21-GA. METHODS: Using value of information methods, we first generated probability distributions of survival and costs for decision making with and without the 21-GA alongside traditional risk prediction. These served as the input to a comparison of 3 alternative study designs: a retrospective observational study to update risk classification from the 21-GA, a prospective observational study to estimate prevalence of chemotherapy use, and a randomized controlled trial (RCT) of the 21-GA predictive value. RESULTS: We found that current evidence strongly supports the use of the 21-GA in intermediate- and high-risk women. Further research should focus on low-risk women, among whom the cost-effectiveness findings remained equivocal. For this population, we identified a high value of reducing uncertainty in the 21-GA use for all proposed research studies. The RCT had the greatest potential to efficiently reduce the likelihood of choosing a suboptimal strategy, providing a value between $162 million and $1.1 billion at willingness-to-pay thresholds of $150 000 to $200 000/quality-adjusted life years. CONCLUSION: Future research to inform 21-GA decision making is of high value. The RCT of the 21-GA predictive value has the greatest potential to efficiently reduce decision uncertainty around 21-GA use in women with low-risk early-stage breast cancer.
Keywords:
21-gene assay; breast cancer; cost-effectiveness; decision making; decision uncertainty; gene expression profiling; precision medicine; research design and prioritization; value of information
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