The Potential Value-Based Price of a Multi-Cancer Early Detection Genomic Blood Test to Complement Current Single Cancer Screening in the USA.

BACKGROUND: Multi-cancer early detection (MCED) testing could increase detection of cancer at early stages, when survival outcomes are better and treatment costs are lower, but is expected to increase screening costs. This study modeled an MCED test for 19 solid cancers in a US population and estimated the potential value-based price (the maximum price to meet a given willingness to pay) of the MCED test plus current single cancer screening (usual care) compared to usual care alone from a third-party payer perspective over a lifetime horizon. METHODS: A hybrid cohort-level state-transition and decision-tree model was developed to estimate the clinical and economic outcomes of annual MCED testing between age 50 and 79 years. The impact on time and stage of diagnosis was computed using an interception modeling approach, with the consequences of cancer modeled based on stage at diagnosis. The model parameters were mainly sourced from the literature, including a published case-control study to inform MCED test performance. All costs were inflated to 2021 US dollars. RESULTS: Multi-cancer early detection testing shifted cancer diagnoses to earlier stages, with a 53% reduction in stage IV cancer diagnoses, resulting in longer overall survival compared with usual care. Addition of MCED decreased per cancer treatment costs by $5421 and resulted in a gain of 0.13 and 0.38 quality-adjusted life-years across all individuals in the screening program and those diagnosed with cancer, respectively. At a willingness-to-pay threshold of $100,000 per quality-adjusted life-year gained, the potential value-based price of an MCED test was estimated at $1196. The projected survival of individuals diagnosed with cancer and the number of cancers detected at an earlier stage by MCED had the greatest impact on outcomes. CONCLUSIONS: An MCED test with high specificity would potentially improve long-term health outcomes and reduce cancer treatment costs, resulting in a value-based price of $1196 at a $100,000/quality-adjusted life-year willingness-to-pay threshold.

Economic evaluation of azoles as primary prophylaxis for the prevention of invasive fungal infections in Spanish patients undergoing allogeneic haematopoietic stem cell transplant.

Patients undergoing allogeneic haematopoietic stem cell transplantation (alloHSCT) are at risk of developing invasive fungal infections (IFIs). Even with introduction of oral triazole antifungal agents (fluconazole, itraconazole, posaconazole and voriconazole) IFI-associated morbidity and mortality rates and economic burden remain high. Despite their proven efficacy, it is currently unknown which is the most cost-effective antifungal prophylaxis (AFP) agent. To determine the costs and outcomes associated with AFP, a decision-analytic model was used to simulate treatment in a hypothetical cohort of 1000 patients undergoing alloHSCT from the perspective of the Spanish National Health System. Generic itraconazole was the least costly AFP (€162) relative to fluconazole (€500), posaconazole oral suspension (€8628) or voriconazole (€6850). Compared with posaconazole, voriconazole was associated with the lowest number of breakthrough IFIs (36 vs 60); thus, the model predicted fewer deaths from breakthrough IFI for voriconazole (24) than posaconazole (33), and the lowest predicted costs associated with other licensed antifungal treatment and IFI treatment in a cohort of 1000. Voriconazole resulted in cost savings of €4707 per patient compared with posaconazole. Itraconazole demonstrated a high probability of being cost-effective. As primary AFP in alloHSCT patients 180 days posttransplant, voriconazole was more likely to be cost-effective than posaconazole regarding cost per additional IFI and additional death avoided.

Systematic review and mixed treatment comparison meta-analysis of randomized clinical trials of primary oral antifungal prophylaxis in allogeneic hematopoietic cell transplant recipients.

BACKGROUND: Antifungal prophylaxis is a promising strategy for reducing invasive fungal infections (IFIs) in allogeneic hematopoietic cell transplant (alloHCT) recipients, but the optimum prophylactic agent is unknown. We used mixed treatment comparison (MTC) meta-analysis to compare clinical trials examining the use of oral antifungals for prophylaxis in alloHCT recipients, with the goal of informing medical decision-making. METHODS: Randomized controlled trials (RCTs) of fluconazole, itraconazole, posaconazole, and voriconazole for primary antifungal prophylaxis were identified through a systematic literature review. Outcomes of interest (incidence of IFI/invasive aspergillosis/invasive candidiasis, all-cause mortality, and use of other antifungals) were extracted from eligible RCTs and incorporated into a Bayesian hierarchical random-effects MTC. RESULTS: Five eligible RCTs, randomizing 2147 patients in total, were included. Relative to fluconazole, prophylaxis with itraconazole (odds ratio [OR]: 0.52; interquartile range [IQR]: 0.35-0.76), posaconazole (OR: 0.56; IQR: 0.32-0.99), and voriconazole (OR: 0.46; IQR: 0.28-0.73) reduced incidence of overall proven/probable IFI. Posaconazole (OR: 0.31; IQR: 0.17-0.58) and voriconazole (OR: 0.33; IQR: 0.17-0.58) prophylaxis reduced proven/probable invasive aspergillosis more than itraconazole (OR: 0.68; IQR: 0.42-1.12). All-cause mortality was similar across all mould-active agents. CONCLUSION: As expected, mould-active azoles prevented IFIs, particularly invasive aspergillosis, more effectively than fluconazole in alloHCT recipients. The paucity of comparative efficacy data suggests that other factors such as long-term tolerability, availability of intravenous formulations, local IFI epidemiology, and drug costs may need to form the basis for selection among the mould-active azoles.

Effectiveness of a Patient Support Program in Supporting Access to Therapy for Solid Tumor Malignancies.

Background: Certain governmental agencies, patient advocacy organizations, and pharmaceutical manufacturers have implemented programs to assist patients in overcoming barriers to accessing healthcare. Recently, such programs have expanded their services, helping both uninsured and insured patients to navigate the complex healthcare system, and assisting with increasing out-of pocket costs and copays for the drugs. Objective: To better understand the effect of patient support programs on access to therapy for solid tumor malignancies, this study evaluated service use, case outcomes, and patient characteristics from a manufacturer-sponsored program in the United States. Methods: Sociodemographic characteristics, services use rates, and outcomes by case and insurance type were evaluated at the patient- and case-level in a random sample of patients prescribed nab-paclitaxel for solid tumor malignancies who enrolled in the Celgene Patient Support (CPS) program (April 2011-November 2013). Results: This analysis included 4566 patients (8134 cases); most patients were female (64.7%), aged <65 years (59.2%), in the South (53.9%), and treated in community settings (87.9%). Patients were primarily insured by Medicare (38.5%) or commercial plans (37.3%), or were uninsured (16.6%). Following benefits investigations for new patients entering the program (98.5%), CPS provided support to obtain free medicine (29.4%), appeal denial of coverage (15.0%), receive commercial co-payment assistance (8.1%), or obtain prior payer authorization (1.3%). Nab-paclitaxel was provided at no cost in 89.4% of cases where patients sought financial support; payer reimbursement was obtained in 63.2% of reimbursement appeals. Of commercially-insured patients who required assistance with co-payments and met financial criteria, 93.3% received a mean of $597 in co-payment support. Conclusion: The CPS program was successful in gaining access to therapy. Healthcare providers and both insured or uninsured patients accessed CPS for prior authorization/precertification, appeals support, and financial support through the Free Medication Program and the Commercial Co-Pay program.

Cost-effectiveness of a FISH assay for the diagnosis of melanoma in the USA.

OBJECTIVE: The authors evaluated the cost-effectiveness of a FISH assay in melanoma diagnosis in the USA. METHOD: A model was developed simulating the addition of FISH to the diagnosis of suspected melanoma. A decision analytic module simulated diagnosis using microscopic assessment alone versus addition of FISH (sensitivity: 92%; specificity: 94%). The authors simulated a clinical setting in which an initial excisional biopsy microscopic assessment (sensitivity: 73%; specificity: 78%) was followed by dermatopathologist assessment (sensitivity: 89%; specificity: 79%) for inconclusive results. Diagnostic strategies 1 and 2 added FISH to the initial and dermatopathologist assessments, respectively. A Markov outcomes module simulated patients' remaining lifetime, including treatment. RESULTS: In diagnostic strategies 1 and 2, the cost per quality-adjusted life year gained was US$14,930 and 43,925, respectively, versus no FISH. Cost per misdiagnosis avoided was US$3292 and 3759, respectively. Sensitivity and specificity without FISH were both ≥88%; however, addition of FISH exceeded US$100,000/quality-adjusted life year. CONCLUSION: In specific clinical settings, FISH could be cost effective for melanoma diagnosis.