Willingness to pay for an mRNA-based anti-cancer treatment: results from a contingent valuation study in Israel.

BACKGROUND: mRNA technology is currently being investigated for a range of oncology indications. We assessed the willingness to pay (WTP) of the general population in Israel for a hypothetical novel mRNA-based treatment for oncology indications. METHODS: We used a contingent valuation methodology to elicit WTP using a web-based questionnaire. A sample of adult participants were presented with a hypothetical scenario in which an mRNA-based intervention increased the likelihood of a cure for various cancer types from 20% to 40% (half of the sample), or 60% (the other half of the sample). RESULTS: 531 respondents completed the questionnaire. The mean, median and mode WTP for the proposed hypothetical treatment in both scenarios were ILS65,000 (± ILS114,000), ILS20,000 and ILS50,000, respectively (1USD = 3.4ILS). The WTP was skewed towards zero, and 9.6% of the respondents were not willing to pay any amount. WTP higher amounts was significantly associated with higher income (p < 0.01), self-reported good health (p < 0.05), supplementary health insurance (p < 0.05), Jews compared to other populations (p < 0.01), interest in technology (p < 0.001) and a tendency to adopt medical innovations (p < 0.001). No statistical difference between the 40% vs. the 60% potential cure scenarios was found. Logistic and OLS regressions indicated that age, religion, income, and interest in adopting medical innovations were the best predictors of respondents' WTP. CONCLUSION: Despite the scientific breakthroughs in oncology treatment over the last few decades, many types of cancer are still incurable. Given the expected development of innovative mRNA-based treatments for cancer, these results should inform policymakers, the pharmaceutical industry and other stakeholders on the future coverage and reimbursement of these technologies incorporating patients' and societal views. To date, WTP considerations have not been given much weight in prioritization of drug reimbursement processes, neither in Israel nor in other countries. As a pioneer in adoption of the mRNA technology, Israel can also lead the incorporation of WTP considerations in this field.

Willingness to pay for cancer prevention, screening, diagnosis, and treatment: a systematic review.

INTRODUCTION: Willingness to pay (WTP) studies examine the maximum amount of money an individual is willing to pay for a specified health intervention, and can be used to inform coverage and reimbursement decisions. Our objectives were to assess how people value cancer-related interventions, identify differences in the methodologies used, and review the trends in studies' publication. AREAS COVERED: We extracted PubMed and EconLit articles published in 1997-2020 that reported WTP for cancer-related interventions, characterized the methodological differences and summarized each intervention's mean and median WTP values. We reviewed 1,331 abstracts and identified 103 relevant WTP studies, of which 37 (36%) focused on treatment followed by screening (26), prevention (21), diagnosis (7) and other interventions (12). The methods used to determine WTP values were primarily discrete-choice questions (n = 54, 52%), bidding games (15), payment cards (12) and open-ended questions (12). We found a wide variation in WTP reported values ranged from below $100 to over $20,000. EXPERT OPINION: The WTP literature on oncology interventions has grown rapidly. There is considerable heterogeneity with respect to the type of interventions and diseases assessed, the respondents' characteristics, and the study methodologies. This points to the need to establish international guidelines for best practices in this field.

Evaluation of a universal hepatitis B vaccination program and antenatal screening for hepatitis B surface antigen: Results from a real-world study 2015-2016.

BACKGROUND AND AIMS: Universal vaccination against hepatitis B virus (HBV) in infancy was implemented in Israel in 1992. This population-based study aimed to evaluate the coverage rate and cost-benefit of the HBV vaccination program among infants in Israel and the Hepatitis B surface antigen (HBsAg) status in their mothers. METHODS: Using the database of a health maintenance organization with 2 million members, we retrospectively identified, all the infants born in 2015-2016 and their mothers. Maternal data collected included age, ethnicity, country of birth and HBsAg status during pregnancy. HBV vaccination coverage among infants was calculated. A cost-benefit analysis of the HBV vaccination program was conducted based on the actual costs of HBV infection treatments in all HBsAg positive mothers. RESULTS: Our cohort included 72,792 mothers who gave birth to 77,572 live infants. A total of 71,107 (97.7%) mothers were screened for HBV during pregnancy, of them 124 (0.2%), who gave birth to 132 infants were HBsAg positive. HBV vaccination coverage rates were 94%, 93% and 89%, for the first, second and third dose, respectively. Birth dose coverage of 95% among infants born to HBsAg positive mothers was significantly higher compared to HBsAg negative or unscreened mothers (p < 0.001). The percentage of HBsAg positivity among mothers who were born in Israel, the Former Soviet Union or Ethiopia, were 0.1%, 0.8% and 5%, respectively (p < 0.001). Ethnic differences were not found between HBsAg positive and HBsAg negative mothers. Calculated benefit-to-cost ratios were 1.24:1 and 4.15:1, with and without antenatal HBsAg screening, respectively. CONCLUSIONS: The Israeli vaccination program against HBV infection is epidemiologically and economically justified. High coverage rates among infants born to HBsAg positive mothers reflect very good adherence to the vaccination program and antenatal screening. Higher HBsAg positivity rates among immigrant mothers identify a high-risk population for HBV infection.

Mature Versus Registration Studies of Immuno-Oncology Agents: Does Value Improve With Time?

PURPOSE: A unique feature of immuno-oncology agents is the potential for durable survival for a subset of patients; however, this benefit usually cannot not be seen in the early published data used for regulatory approval. Value frameworks developed by ASCO and the European Society for Medical Oncology (ESMO) assess the clinical benefit demonstrated in clinical trials. Proven benefit may change with time as more mature data are available. Our objective was to evaluate the impact of mature data for immuno-oncology agents on ASCO and ESMO scores and to examine the concordance of these frameworks using more mature data. METHODS: We reviewed Food and Drug Administration (FDA) approvals for immuno-oncology agents between 2011 and 2017, calculated the ASCO-Net Health Benefit (NHB) score and ESMO-Magnitude of Clinical Benefit Score (MCBS), checked which agents fulfilled the criteria of being rewarded for durable survival, assessed the concordance between models using the Spearman correlation test, and compared the initial results of registration studies with mature follow-up data from the same studies. RESULTS: The FDA approved 27 solid tumor indications for immuno-oncology agents between 2011 and 2017. The correlation between ASCO-NHB score and ESMO-MCBS was high (0.88). Mature follow-up data were available for 13 of these indications, in which 6 studies were found to have improved in the grade of ASCO and/or ESMO value frameworks, whereas 2 cases were downgraded in the scale. CONCLUSION: Despite different approaches, the high concordance between ASCO and ESMO value frameworks indicates that both models reward treatments as beneficial for the same immuno-oncology agents. Mature data with longer follow-up reaffirmed most of the findings found in the evaluation in the initially published registration studies.

Median Survival or Mean Survival: Which Measure Is the Most Appropriate for Patients, Physicians, and Policymakers?

INTRODUCTION: Understanding the efficacy of treatments is crucial for patients, physicians, and policymakers. Median survival, the most common measure used in the outcome reporting of oncology clinical trials, is easy to understand; however, it describes only a single time point. The interpretation of the hazard ratio is difficult, and its underlying statistical assumptions are not always met. The objective of this study was to evaluate alternative measures based on the mean benefit of novel oncology treatments. MATERIALS AND METHODS: We reviewed all U.S. Food and Drug Administration (FDA) approvals for oncology agents between 2013 and 2017. We digitized survival curves as reported in the clinical trials used for the FDA approvals and implemented statistical transformations to calculate for each trial the restricted mean survival time (RMST), as well as the mean survival using Weibull distribution. We compared the mean survival with the median survival benefit in each clinical trial. RESULTS: The FDA approved 83 solid tumor indications for oncology agents between 2013 and 2017, of which 27 approvals based on response rates, whereas 49 approvals were based on survival endpoints (progression-free survival and overall survival). The average improvement in median overall survival or progression-free survival was 4.6 months versus 3.6 months improvement in the average RMST and 6.1 months improvement in mean survival using Weibull distribution. CONCLUSION: Mean survival may supply valuable information for different stakeholders. Its inclusion should be considered in the reporting of prospective clinical trials. IMPLICATIONS FOR PRACTICE: Mean survival may supply valuable information for different stakeholders. Its inclusion should be considered in the reporting of clinical trials.

Association of Immunotherapy With Durable Survival as Defined by Value Frameworks for Cancer Care.

IMPORTANCE: Modern immuno-oncology agents have generated great excitement because of their potential to provide durable survival for some patients. However, there is concern regarding the cost of cancer care, and multiple frameworks have been developed to assess value. The American Society of Clinical Oncology (ASCO) framework awards bonus points if substantial durable survival is demonstrated. OBJECTIVE: To assess whether modern immuno-oncology agents reach defined efficacy thresholds in value frameworks. DESIGN, SETTING, AND PARTICIPANTS: In this analysis, all US Food and Drug Administration (FDA) approvals for immuno-oncology agents between March 2011 and August 2017 were reviewed. Data required for the ASCO framework were collected, specifically improvement in proportion of patients alive with the test regimen and survival rate with standard treatment. MAIN OUTCOMES AND MEASURES: Awarding of bonus points for durable survival based on the ASCO criteria. RESULTS: Twenty-three metastatic indications for 6 immuno-oncology agents (ipilimumab, pembrolizumab, nivolumab, atezolizumab, avelumab, and durvalumab) were approved by the FDA from March 2011 to August 2017. Ten (43%) of the approvals were based on survival end points, while 13 (57%) were based on response rates. Only 3 drug indications fulfilled the threshold defined for the survival rate of patients receiving standard care (minimum 20%). Nine indications achieved the required level of improvement in proportion to patients alive in the test regimen compared with the standard (above 50%). There was overlap between these 2 criteria for 3 drug indications, allowing them to gain the durable survival bonus points awarded by the ASCO framework. CONCLUSIONS AND RELEVANCE: Durable survival and response rates of modern immuno-oncology agents are rarely recognized as significant by current oncology value frameworks. This may be due to insufficient demonstration of efficacy of such agents or inappropriately calibrated value frameworks.

Does drug price-regulation affect healthcare expenditures?

BACKGROUND: Increasing health costs in developed countries are a major concern for decision makers. A variety of cost containment tools are used to control this trend, including maximum price regulation and reimbursement methods for health technologies. Information regarding expenditure-related outcomes of these tools is not available. OBJECTIVE: To evaluate the association between different cost-regulating mechanisms and national health expenditures in selected countries. METHODS: Price-regulating and reimbursement mechanisms for prescription drugs among OECD countries were reviewed. National health expenditure indices for 2008-2012 were extracted from OECD statistical sources. Possible associations between characteristics of different systems for regulation of drug prices and reimbursement and health expenditures were examined. RESULTS: In most countries, reimbursement mechanisms are part of publicly financed plans. Maximum price regulation is composed of reference-pricing, either of the same drug in other countries, or of therapeutic alternatives within the country, as well as value-based pricing (VBP). No association was found between price regulation or reimbursement mechanisms and healthcare costs. However, VBP may present a more effective mechanism, leading to reduced costs in the long term. CONCLUSIONS: Maximum price and reimbursement mechanism regulations were not found to be associated with cost containment of national health expenditures. VBP may have the potential to do so over the long term.