A Value of Information Analysis of Research on the 21-Gene Assay for Breast Cancer Management.

Kunst NR1, Alarid-Escudero F2, Paltiel AD3, Wang SY4.

Author information

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.

KEYWORDS:

21-gene assay; breast cancer; cost-effectiveness; decision making; decision uncertainty; gene expression profiling; precision medicine; research design and prioritization; value of information