Cost-Effectiveness Analyses of the 21-Gene Assay in Breast Cancer: Systematic Review and Critical Appraisal

Abstract

Purpose Prior studies examining cost effectiveness of the 21-gene assay (Oncotype DX [ODX]) for women with hormone receptor-positive, early-stage breast cancer have yielded disparate results. We aimed to explore why these analyses may have yielded different conclusions. Methods We conducted a systematic literature review of cost-effectiveness analyses (CEAs) of ODX. We examined the extent to which the structure of CEA modeling, the assumptions of the models, and the selection of input parameters influenced cost-effectiveness estimates. We also explored the prevalence of industry funding and whether industry funding was associated with study designs favoring ODX. Results We identified 27 analyses, 15 of which received industry funding. In 18 studies, the clinical characteristics (eg, tumor size and grade) commonly used to make chemotherapy decisions were not incorporated into simulation modeling; thus, these studies would favor ODX being cost effective and might not reflect clinical practice. Most studies ignored the heterogeneous effect of ODX on chemotherapy use; only five studies assumed that ODX would increase chemotherapy use for clinically low-risk patients but decrease chemotherapy use for clinically high-risk patients. No study used population-based joint distributions of ODX recurrence score and tumor characteristics, and 12 studies inappropriately assumed that chemotherapy would increase distant recurrence for the low recurrence score group; both approaches overestimated the benefits of ODX. Industry-funded studies tended to favor ODX; all five studies that reported ODX as being cost saving were industry funded. In contrast, two studies that reported an incremental cost-effectiveness ratio > $50,000 per quality-adjusted life-year were not funded by industry. Conclusion Although a majority of published analyses indicated that ODX is cost effective, they incorporated study designs that can increase the risk of bias.

Incorporating Tumor Characteristics to Maximize 21-Gene Assay Utility: A Cost-Effectiveness Analysis

“…45,46 To estimate prevalence or distributions of RS, population-based studies are preferable to randomized controlled trials (RCTs) because of the external validity consideration. 14 Based on our population-based study, only 3% of patients who were classified as low-risk patients (according to their PREDICT estimation) had RS≥31. Our results differed substantially from those of post hoc analyses of a subset of participants enrolled in an RCT 47 that found that approximately 15% of the low-risk group (based on AO estimation) had RS≥31 (supplemental eTable 8).…”

“…[8][9][10][11][12][13] However, several important methodologic limitations may have diminished the accuracy of previous cost-effectiveness analyses (CEAs). 14 First, these studies tended to combine all patients into a single group, [9][10][11] irrespective of their clinical and pathologic features. Such an approach, ignoring tumor characteristics when evaluating ODX, is not consistent with actual clinical practice because it assumes that all patients would be treated without consideration of their clinical characteristics.…”

Chemotherapy Costs and 21-Gene Recurrence Score Genomic Testing Among Medicare Beneficiaries With Early-Stage Breast Cancer, 2005 to 2011

“…[19][20][21] However, not all studies reported declines, and recent critical review of these analyses showed potential biases that may substantially influence study findings. 13 Previous work found a differential impact of RS testing on chemotherapy use, with significant reductions only among Medicare beneficiaries with high-risk disease. 15 For this reason, we hypothesized that the greatest cost reduction with RS testing would occur among younger, healthier patients with highrisk disease.…”

“…[4][5][6][7][8][9][10][11][12] However, these economic models require numerous assumptions and may be influenced substantially by investigator bias. 13 Furthermore, patients' treatment decisions can vary depending on personal preferences and priorities, and they may not follow test-based or physicianrecommended treatment. Contrary to guideline recommendations, some patients with low-risk disease receive RS testing 14 and have a higher likelihood of undergoing chemotherapy than those who do not receive testing.…”

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

“…[15][16][17] Generally, the 21-GA outperforms traditional clinicopathologic information, 18,19 but owing to its high cost, its unrestricted use could impose a substantial economic burden on society. Although several studies have concluded that the 21-GA is cost-effective, [20][21][22] a recent systematic literature review 23 questions their failure to consider a number of factors (eg, patients' clinicopathologic information) that are widely considered by oncologists before making chemotherapy decisions.…”