Value in Health

First-Line Treatment With Atezolizumab Plus Bevacizumab and Chemotherapy for US Patients With Metastatic, Persistent, or Recurrent Cervical Cancer: A Cost-Effectiveness Analysis

The BETAcc clinical trial demonstrated that chemotherapy combined with bevacizumab plus atezolizumab (CBA) significantly prolonged progression-free survival and overall survival in patients with metastatic, persistent, or recurrent cervical cancer. However, to the best of our knowledge, the economic value of using this new therapy for this indication is currently unknown. Therefore, our study aimed to evaluate the cost-effectiveness of CBA for the first-line treatment of metastatic, persistent, or recurrent cervical cancer from the United States healthcare payers perspective. A state-transition Markov model over a 10-year lifetime horizon was developed to compare the cost and effectiveness of CBA with that of chemotherapy plus bevacizumab (CB). The primary outcomes of our study included costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios. One-way sensitivity analysis and probabilistic sensitivity analysis were performed to assess the robustness of the results. CBA was associated with an additional 0.58 QALY at an extra cost of $172 495.90 compared with CB. The incremental cost-effectiveness ratio was $295 972.43/QALY, significantly higher than the willingness-to-pay threshold value of $150 000/QALY. One-way sensitivity analyses revealed that results were most sensitive to the progression-free disease utility, the unit cost of atezolizumab, and progressed disease utility. Probabilistic sensitivity analysis indicated that CBA achieved a 4.3% probability of cost-effectiveness at a $150 000/QALY threshold. To achieve cost-effectiveness, the unit price of atezolizumab must be reduced by approximately 56.6%. CBA treatment is unlikely to be a cost-effective option compared with CB for patients with persistent, recurrent, or metastatic cervical cancer in the United States.

Cost-Effectiveness of Targeted Genetic Testing for Breast and Ovarian Cancer: A Systematic Review

Targeted genetic testing is a tool to identify women at increased risk of gynaecological cancer. This systematic review evaluates the results and quality of cost-effectiveness modeling studies that assessed targeted genetic-based screen-and-treat strategies to prevent breast and ovarian cancer. Using MEDLINE and databases of the Centre for Reviews and Dissemination, we searched for health economic modeling evaluations of targeted genetic-based screen-and-treat strategies to prevent inheritable breast and ovarian cancer (until August 2020). The incremental cost-effectiveness ratios (ICERs) were compared. Methodological variations were addressed by evaluating the model conceptualizations, the modeling techniques, parameter estimation and uncertainty, and transparency and validation of the models. Additionally, the reporting quality of each study was assessed. Eighteen studies met our inclusion criteria. From a payer perspective, the ICERs of (1) BRCA screening for high-risk women without cancer ranged from dominating the no test strategy to an ICER of $21 700/quality-adjusted life years (QALY). In studies that evaluated (2) BRCA cascade screening (ie, screening of women with cancer plus their unaffected relatives) compared with no test, the ICERs were between $6500/QALY and $50 200/QALY. Compared with BRCA alone, (3) multigene testing in women without cancer had an ICER of $51 800/QALY (one study), while for (4) multigene-cascade screening the ICERs were $15 600/QALY, $56.500/QALY, and $69 600/QALY for women in the United Kingdom, Norway, and the United States, respectively (2 studies). More recently published studies showed a higher methodological and reporting quality. Targeted BRCA or multiple gene screening is likely to be cost-effective. Methodological variations could be decreased by the development of a reference model, which may serve as a tool for validation of present and future cost-effectiveness models.

The Impact of Broader Value Elements on Cost-Effectiveness Analysis: Two Case Studies

This study aimed to explore the impact of including broader value elements in cost-effectiveness analyses by presenting 2 case studies, one on human papillomavirus (HPV) infection and one on early-stage Hodgkin's lymphoma (ESHL). We identified broader value elements (eg, patient and caregiver time, spillover health effects, productivity) from the Second Panel's Impact Inventory and the ISPOR Special Task Force's value flower. We then evaluated the cost-effectiveness of HPV vaccination versus no vaccination (case 1) and combined modality therapy (CMT) versus chemotherapy alone for treatment of adult ESHL (case 2) using published simulation models. For each case study, we compared incremental cost-effectiveness ratios considering health sector impacts only (the "base-case" scenario) with incremental cost-effectiveness ratios incorporating broader value elements. For vaccination of US girls against HPV before sexual debut versus no vaccination, the base-case result was $38 334 per disability-adjusted life-year averted. Including each broader value element made cost-effectiveness progressively more favorable, with HPV vaccination becoming cost-saving (ie, reducing costs and averting more disability-adjusted life-years) when the analysis incorporated productivity costs. For CMT versus chemotherapy alone in patients with ESHL, the base-case result indicated that CMT was cost-saving. Including all elements made this treatment's net monetary benefits (the sum of its averted resource costs and the net value of its health impacts) less favorable, even as the contribution from CMT's near-term health benefits grew. Including broader value elements can substantially influence cost-effectiveness ratios, although the direction and the magnitude of their impact can differ across interventions and disease context.

Financial Toxicity of Withdrawn Poly (Adenosine Diphosphate Ribose) Polymerase Inhibitor Indications for Ovarian Cancer

We sought to quantify exposure to and financial impacts of poly (adenosine diphosphate ribose) polymerase inhibitor (PARPi) treatments for eventually withdrawn ovarian cancer indications. We identified in Optum's deidentified Clinformatics® Data Mart database 1695 patients with ovarian cancer diagnoses who received olaparib, rucaparib, or niraparib between January 2015 and September 2021. We describe PARPi use and out-of-pocket, total healthcare, and PARPi spending among patients with ovarian cancer with 3 or more previous lines of therapy. Of the 1695 patients who received PARPi, 254 were estimated to have been heavily pretreated and exposed to eventually withdrawn indications. Cumulative total medical and pharmacy costs for these patients were $53 392 184; PARPi costs accounted for 34%. Median PARPi cost per patient was $43 347. Cumulative out-of-pocket costs totaled $533 281. Potential patient harm, including financial toxicity, might have been mitigated through more stringent drug approval requirements.

Revising the Suspected-Cancer Guidelines: Impacts on Patients’ Primary Care Contacts and Costs

This study aimed to explore the impact of revising suspected-cancer referral guidelines on primary care contacts and costs. Participants had incident cancer (colorectal, n = 2000; ovary, n = 763; and pancreas, n = 597) codes in the Clinical Practice Research Datalink or England cancer registry. Difference-in-differences analyses explored guideline impacts on contact days and nonzero costs between the first cancer feature and diagnosis. Participants were controls ("old National Institute for Health and Care Excellence [NICE]") or "new NICE" if their index feature was introduced during guideline revision. Model assumptions were inspected visually and by falsification tests. Sensitivity analyses reclassified participants who subsequently presented with features in the original guidelines as "old NICE." For colorectal cancer, sensitivity analysis (n = 3481) adjusted for multimorbidity burden. Median contact days and costs were, respectively, 4 (interquartile range [IQR] 2-7) and £117.69 (IQR £53.23-£206.65) for colorectal, 5 (IQR 3-9) and £156.92 (IQR £78.46-£272.29) for ovary, and 7 (IQR 4-13) and £230.64 (IQR £120.78-£408.34) for pancreas. Revising ovary guidelines may have decreased contact days (incidence rate ratio [IRR] 0.74; 95% confidence interval 0.55-1.00; P = .05) with unchanged costs, but parallel trends assumptions were violated. Costs decreased by 13% (equivalent to -£28.05, -£50.43 to -£5.67) after colorectal guidance revision but only in sensitivity analyses adjusting for multimorbidity. Contact days and costs remained unchanged after pancreas guidance revision. The main analyses of symptomatic patients suggested that prediagnosis primary care costs remained unchanged after guidance revision for pancreatic cancer. For colorectal cancer, contact days and costs decreased in analyses adjusting for multimorbidity. Revising ovarian cancer guidelines may have decreased primary care contact days but not costs, suggesting increased resource-use intensity; nevertheless, there is evidence of confounding.

Demand for Cancer Screening Services: Results From Randomized Controlled Discrete Choice Experiments

Low uptake of cancer screening services is a global concern. Our aim was to understand factors that influence the screening decision, including screening and treatment subsidies and a gain-frame message designed to present screening as a win-win. We analyzed preferences for mammography and Pap smear among women in Singapore by means of discrete choice experiments while randomly exposing half of respondents to a gain-framed public health message promoting the benefits of screening. Results showed that the message did not influence stated uptake, and given the levels shown, respondents were influenced more by treatment attributes, including effectiveness and out-of-pocket cost should they test positive, than by screening attributes, including the offer of a monetary incentive for screening. Respondents also underestimated the survival chances of screen-detected breast and cervical cancers. Combined, these findings suggest that correcting misconceptions about screen-detected cancer prognosis or providing greater financial protection for those who test positive could be more effective and more cost-effective than subsidizing screening directly in increasing screening uptakes.

Toward the Implementation of a Value Framework for Diagnostic Technologies: Operationalization, Piloting, and Validation in Latin America

In 2020, a group of 30 stakeholders from Latin America established 15 criteria for a diagnostic technologies value framework (D-VF) to help assess and inform decisions on diagnostic technologies. This article aims to present the operationalization, piloting, and initial validation of the framework for its implementation. This work was carried out collaboratively with a variety of stakeholders. Three sequential phases were undertaken: (1) operationalization of the D-VF through a literature search for conceptual definitions and assessment tools, (2) piloting of the D-VF through a rapid health technology assessment document applying the methodology of the framework, and (3) a face validation process conducted through a virtual workshop, where usefulness and implementation aspects of the framework were assessed. The operationalization of the framework was conducted, and a methodological user guide was published. The D-VF criteria were applied in a health technology assessment document on human papilloma virus testing in cervical cancer screening. Also, an open-access training program was developed. Stakeholders agreed on the usefulness of the D-VF for assessment and decision-making stages of diagnostic technologies. However, they highlighted the need to improve technical capacities and the potential for added complexity when applying a D-VF with many criteria. The absence of an established value framework for diagnostic technologies in Latin America and the potential for strengthening technical capacities made the project valuable to those involved. The diagnostic technologies value framework was shown to be fit for implementation in real-life decision-making settings after the operationalization, piloting, and initial validation phases. Further experiences are important to support its implementation.

Tackling Challenges in Assessing the Economic Value of Tumor-Agnostic Therapies: A Cost-Effectiveness Analysis of Pembrolizumab as a Case Study