Value of Expanding First-Line Treatment Choices: New Metrics for Economic Evaluation

Abstract

BackgroundHealthcare payers often implement coverage policies to restrict the usage of high-cost, novel first-line treatments. Step therapy policy is a typical example, requiring patients to fail a less costly medication before accessing a more costly treatment, even if both have been approved for first-line use. A cost-effectiveness analysis (CEA) can be carried out to inform the restriction policy by comparing a new first-line treatment versus the existing one. However, the traditional approach fails to recognize treatment effect heterogeneity, real-world treatment selection, and the resources used to implement policies. To overcome these limitations, this study aimed to develop a general framework to better evaluate the cost-effectiveness of expanding versus restricting first-line treatment choices. I illustrated this framework using the case of abiraterone acetate plus prednisone (AAP) for metastatic hormone-sensitive prostate cancer (mHSPC). In Aim 1, I formulated mathematical expressions for the new cost-effectiveness metrics under the proposed framework. Aim 2 assessed whether clinical evidence of age-related treatment effect heterogeneity of AAP was associated with its differential utilization among men with mHSPC. Finally, Aim 3 applied the proposed framework to the empirical case study of AAP combined with androgen deprivation therapy (ADT) as a first-line treatment for mHSPC. MethodsIn Aim 1, I formulated an incremental cost-effectiveness ratio (ICER) metric to compare an expanded versus a restricted choice set (CS) of first-line treatments, accounting for clinical evidence-driven treatment selection and policy implementation costs. I also developed the metrics of expected value of expanding choices (EVEC) and expected value of perfect information (EVPI) to quantify the value resulting from an expansion policy and future studies to eliminate uncertainties around treatment effect heterogeneity, respectively. In Aim 2, A retrospective difference-in-differences (DID) event study was conducted among newly diagnosed mHSPC men using TriNetX electronic medical records data. I analyzed the change in the uptake rate of AAP before versus after the publication of clinical trial evidence among mHSPC men aged <70 years compared with ≥70 years old. In Aim 3, I built a partitioned survival model to assess the cost-effectiveness of choice sets with versus without the option of ADT + AAP for mHSPC from a societal perspective. I compared the results from the proposed CEA framework with those from the traditional CEA. ResultsIn Aim 1, I presented the mathematical formulas for ICER(CS), EVEC, and EVPI with stylized examples to illustrate the calculation. In Aim 2, mHSPC men aged <70 had 3.5% (95% confidence interval: 1.2%–5.8%, P = 0.003) additional AAP uptake relative to men aged ≥70 years during the first six months following the publication of clinical evidence. This DID estimate represents an uptake rate that is approximately three times higher than would have been expected had the younger group followed the uptake trends as the older group. In addition, these DID estimates were consistent throughout the observed post-publication period. In Aim 3, traditional CEA produced an ICER of $102,793 and $210,223/quality-adjusted life year (QALY) gained when comparing ADT + AAP with ADT alone and ADT + D, respectively. The proposed framework led to an ICER(CS) of $125,754/QALY gained. The population EVEC varied from -$236 million to $539 million at a willingness-to-pay (WTP) threshold of $50,000 to $300,000/QALY gained. The ideal EVPI at the population level ranged from $63 million to $288 million over the same range of WTP. Conclusions The proposed economic evaluation framework provides decision makers with more policy-relevant metrics to assess the potential social value of expanding first-line treatment choices. The empirical case study suggests that the proposed and traditional CEA framework may lead to different economic value estimates of first-line AAP for mHSPC.