Establishing cost-effectiveness of genetic targeting of cancer therapies

The clinical benefit of a new genomic instrument, the 70-gene signature for breast cancer patients, is being evaluated in a randomised clinical trial. The early, controlled implementation process is supported by a Constructive Technology Assessment to help decision-making in an uncertain time of development

Establishing cost-effectiveness of genetic targeting of cancer therapies\ud

The clinical benefit of a new genomic instrument, the 70-gene signature\ud for breast cancer patients, is being evaluated in a randomised clinical\ud trial. The early, controlled implementation process is supported by a\ud Constructive Technology Assessment to help decision-making in an\ud uncertain time of developmen

Differences in time to patient access to innovative cancer medicines in six European countries

Patients across Europe face inequity regarding access to anticancer medicines. While access is typically evaluated through reimbursement status or sales data, patients can receive first access through early access programs (EAPs) or off-label use. This study aims to assess the time to patient access at the hospital level, considering different indications and countries. (Pre-)registered access to six innovative medicines (Olaparib, Niraparib, Ipilimumab, Osimeritinib, Nivolumab and Ibritunib) was measured using a cross-sectional survey. First patient access to medicines and indications were collected using the hospital databases. Nineteen hospitals from Hungary, Italy, the Netherlands, Belgium, Switzerland and France participated. Analysis showed that some hospitals achieved patient access before national reimbursement, primarily through EAPs. The average time from EMA-approval to patient access for these medicines was 2.1 years (Range: −0.9-7.1 years). Hospitals in Italy and France had faster access compared to Hungary and Belgium. Variation was also found within countries, with specialized hospitals (x̄: −0.9 years; SD: 2.0) more likely to provide patient access prior to national reimbursement than general hospitals (x̄: 0.4 years; SD: 2.9). Contextual differences were observed, with EAPs or off-label use being more prevalent in Switzerland than Hungary. Recent EMA-approved indications and drug combinations reached patients at a later stage. Substantial variation in patient access time was observed between and within countries. Improving pricing and reimbursement timelines, fostering collaboration between national health authorities and market authorization holders, and implementing nationally harmonized, data-generating EAPs can enhance timely and equitable patient access to innovative cancer treatments in Europe.</p

Duty to recontact in genomic cancer care:A tool helping to assess the professional's responsibility

Tumour DNA and germline testing, based on DNA-wide sequencing analysis, are becoming more and more routine in clinical-oncology practice. A promising step in medicine, but at the same time leading to challenging ethicolegal questions. An important one is under what conditions individuals (patients and their relatives, research participants) should be recontacted with new information, even if many years have passed since the last contact. Based on legal- and ethical study, we developed a tool to help professionals to decide whether or not to recontact an individual in specific cases. It is based on four assessment criteria: (1) professional relationship (2) clinical impact (3) individual's preferences and (4) feasibility. The tool could also serve as a framework for guidelines on the topic.</p

Affordable Prices Without Threatening the Oncological R&D Pipeline—An Economic Experiment on Transparency in Price Negotiations

The high prices of innovative medicines endanger access to care worldwide. Sustainable prices need to be affordable while sufficiently incentivizing research and development (R&D) investments. A proposed solution is increased transparency. Proponents argue that price and R&D cost confidentiality are drivers of high prices. On the contrary, supporters of confidentiality claim that confidentiality enables targeted discounts which make treatments affordable; moreover, pharmaceutical companies argue that R&D investments would suffer with more transparency. Despite the political relevance, limited empirical evidence exists on the effects of transparency regulations. We contribute to fill this gap with an experiment where we replicate the EU pharmaceutical market in a laboratory setting. In a randomized controlled study, we analyzed how participants, 400 students located in four European countries, negotiated in the current system of Price Secrecy in comparison with innovative bargaining settings where either prices only (Price Transparency) or prices and R&D costs (Full Transparency) were made transparent to buyers. We found that Price transparency had no statistically significant effect on average prices or number of patients treated and made R&D investments significantly smaller (−16.86%; P: 0.0024). On the other hand, Full Transparency reduced prices (−26%; P: 0.0004) and held the number of patients constant at the level of Price Secrecy. It produced price convergence between countries with low and high health budgets, and, despite lower prices, had no effect on R&D investments. Our findings provide novel evidence that combining price and R&D cost transparency could be an effective policy to contribute to sustainable medicine prices

Exploring the Cost Effectiveness of a Whole-Genome Sequencing-Based Biomarker for Treatment Selection in Patients with Advanced Lung Cancer Ineligible for Targeted Therapy

Objective: We aimed to perform an early cost-effectiveness analysis of using a whole-genome sequencing-based tumor mutation burden (WGS-TMB), instead of programmed death-ligand 1 (PD-L1), for immunotherapy treatment selection in patients with non-squamous advanced/metastatic non-small cell lung cancer ineligible for targeted therapy, from a Dutch healthcare perspective. Methods: A decision-model simulating individual patients with metastatic non-small cell lung cancer was used to evaluate diagnostic strategies to select first-line immunotherapy only or the immunotherapy plus chemotherapy combination. Treatment was selected using PD-L1 [A, current practice], WGS-TMB [B], and both PD-L1 and WGS-TMB [C]. Strategies D, E, and F take into account a patient’s disease burden, in addition to PD-L1, WGS-TMB, and both PD-L1 and WGS-TMB, respectively. Disease burden was defined as a fast-growing tumor, a high number of metastases, and/or weight loss. A threshold of 10 mutations per mega-base was used to classify patients into TMB-high and TMB-low groups. Outcomes were discounted quality-adjusted life-years (QALYs) and healthcare costs measured from the start of first-line treatment to death. Healthcare costs includes drug acquisition, follow-up costs, and molecular diagnostic tests (i.e., standard diagnostic techniques and/or WGS for strategies involving TMB). Results were reported using the net monetary benefit at a willingness-to-pay threshold of €80,000/QALY. Additional scenario and threshold analyses were performed. Results: Strategy B had the lowest QALYs (1.84) and lowest healthcare costs (€120,800). The highest QALYs and healthcare costs were 2.00 and €140,400 in strategy F. In the base-case analysis, strategy A was cost effective with the highest net monetary benefit (€27,300), followed by strategy B (€26,700). Strategy B was cost effective when the cost of WGS testing was decreased by at least 24% or when immunotherapy results in an additional 0.5 year of life gained or more for TMB high compared with TMB low. Strategies C and F, which combined TMB and PD-L1 had the highest net monetary benefit (≥ €76,900) when the cost of WGS testing, immunotherapy, and chemotherapy acquisition were simultaneously reduced by at least 47%, 39%, and 43%, respectively. Furthermore, strategy C resulted in the highest net monetary benefit (≥ €39,900) in a scenario where patients with both PD-L1 low and TMB low were treated with chemotherapy instead of immunotherapy plus chemotherapy. Conclusions: The use of WGS-TMB is not cost effective compared to PD-L1 for immunotherapy treatment selection in non-squamous metastatic non-small cell lung cancer in the Netherlands. WGS-TMB could become cost effective provided there is a reduction in the cost of WGS testing or there is an increase in the predictive value of WGS-TMB for immunotherapy effectiveness. Alternatively, a combination strategy of PD-L1 testing with WGS-TMB would be cost effective if used to support the choice to withhold immunotherapy in patients with a low expected benefit of immunotherapy.</p

Exploring the Cost Effectiveness of a Whole-Genome Sequencing-Based Biomarker for Treatment Selection in Patients with Advanced Lung Cancer Ineligible for Targeted Therapy

Objective: We aimed to perform an early cost-effectiveness analysis of using a whole-genome sequencing-based tumor mutation burden (WGS-TMB), instead of programmed death-ligand 1 (PD-L1), for immunotherapy treatment selection in patients with non-squamous advanced/metastatic non-small cell lung cancer ineligible for targeted therapy, from a Dutch healthcare perspective. Methods: A decision-model simulating individual patients with metastatic non-small cell lung cancer was used to evaluate diagnostic strategies to select first-line immunotherapy only or the immunotherapy plus chemotherapy combination. Treatment was selected using PD-L1 [A, current practice], WGS-TMB [B], and both PD-L1 and WGS-TMB [C]. Strategies D, E, and F take into account a patient’s disease burden, in addition to PD-L1, WGS-TMB, and both PD-L1 and WGS-TMB, respectively. Disease burden was defined as a fast-growing tumor, a high number of metastases, and/or weight loss. A threshold of 10 mutations per mega-base was used to classify patients into TMB-high and TMB-low groups. Outcomes were discounted quality-adjusted life-years (QALYs) and healthcare costs measured from the start of first-line treatment to death. Healthcare costs includes drug acquisition, follow-up costs, and molecular diagnostic tests (i.e., standard diagnostic techniques and/or WGS for strategies involving TMB). Results were reported using the net monetary benefit at a willingness-to-pay threshold of €80,000/QALY. Additional scenario and threshold analyses were performed. Results: Strategy B had the lowest QALYs (1.84) and lowest healthcare costs (€120,800). The highest QALYs and healthcare costs were 2.00 and €140,400 in strategy F. In the base-case analysis, strategy A was cost effective with the highest net monetary benefit (€27,300), followed by strategy B (€26,700). Strategy B was cost effective when the cost of WGS testing was decreased by at least 24% or when immunotherapy results in an additional 0.5 year of life gained or more for TMB high compared with TMB low. Strategies C and F, which combined TMB and PD-L1 had the highest net monetary benefit (≥ €76,900) when the cost of WGS testing, immunotherapy, and chemotherapy acquisition were simultaneously reduced by at least 47%, 39%, and 43%, respectively. Furthermore, strategy C resulted in the highest net monetary benefit (≥ €39,900) in a scenario where patients with both PD-L1 low and TMB low were treated with chemotherapy instead of immunotherapy plus chemotherapy. Conclusions: The use of WGS-TMB is not cost effective compared to PD-L1 for immunotherapy treatment selection in non-squamous metastatic non-small cell lung cancer in the Netherlands. WGS-TMB could become cost effective provided there is a reduction in the cost of WGS testing or there is an increase in the predictive value of WGS-TMB for immunotherapy effectiveness. Alternatively, a combination strategy of PD-L1 testing with WGS-TMB would be cost effective if used to support the choice to withhold immunotherapy in patients with a low expected benefit of immunotherapy.</p

Health state utility and health-related quality of life measures in patients with advanced ovarian cancer

Purpose: Measuring health-related quality of life (HRQoL) in ovarian cancer patients is critical to understand the impact of disease and treatment. Preference-based HRQoL measures, called health state utilities, are used specifically in health economic evaluations. Real-world patient-reported data on HRQoL and health state utilities over the long-term course of ovarian cancer are limited. This study aims to determine HRQoL and health state utilities in different health states of ovarian cancer. Methods: This cross-sectional, multicenter study included patients with stage III-IV ovarian cancer in six health states: at diagnosis, during chemotherapy, after cytoreductive surgery (CRS), after chemotherapy, in remission, and at first recurrence. HRQoL was measured using the European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire C30, and the ovarian cancer-specific module OV28. Health state utilities were assessed using the EuroQol five-dimension five-level (EQ-5D-5L) questionnaire. Descriptive analyses were performed for each health state. Results: Two hundred thirty-two patients participated, resulting in 319 questionnaires. Median age was 66 years. The lowest HRQoL was observed during chemotherapy and shortly after CRS. Physical and role functioning were most affected and the highest symptom prevalence was observed in the fatigue, nausea, pain, dyspnea, gastrointestinal, neuropathy, attitude, and sexuality domains. Patients in remission had the best HRQoL. Mean utility values ranged from 0.709 (±0.253) at diagnosis to 0.804 (±0.185) after chemotherapy.Conclusions: This study provides clinicians with a valuable resource to aid in patient counseling and clinical decision-making. The utilities, in particular, are crucial for researchers conducting economic analyses to inform policy decisions.</p