Valuation of EQ-5D-5L health states from cancer patients' perspective: a feasibility study.

OBJECTIVES: To assess the feasibility of estimating an EQ-5D-5L value set using a small study design in cancer patients and to compare the EQ-5D-5L values based on the preferences of cancer patients with those of the general public. METHODS: Patients with clinically diagnosed cancers were recruited from two hospitals in Shanghai, China. In face-to-face interviews using the EQ-PVT survey, health states were valued by cancer patients using both cTTO and DCE methods. cTTO data was modelled alone or jointly with DCE data. Forty-eight models using different model specifications (cross-attribute level effect [CALE] and additive models), random/fixed effects model assumptions, data heteroscedasticity and censoring were estimated. The best performed model was identified in terms of monotonicity of estimated model coefficients and out-of-sample prediction accuracy. RESULTS: Data collected from 221 cancer patients who participated in the study were included. The hybrid CALE model using both TTO and DCE data performed best in terms of prediction accuracy (Lin's concordance coefficient = 0.989; root mean squared error = 0.058) and suggested that pain/discomfort and anxiety/depression were the most undesirable health problems. Compared to values based on general Chinese public's health preferences, the values based on cancer patients' preferences were much higher and lower for health states characterized by extreme mobility problems and severe/extreme pain or discomfort, respectively. CONCLUSION: This study demonstrated the feasibility of using a small design to develop EQ-5D-5L value sets based on cancer patients' health preferences. Since there were signs of differences between preferences of patients and general population, it may be valuable to develop patient-specific value sets and use them in clinical decision making and economic evaluations.

First-line treatments for advanced renal-cell carcinoma with immune checkpoint inhibitors: systematic review, network meta-analysis and cost-effectiveness analysis.

BACKGROUND: Immune checkpoint inhibitors (ICIs) are effective for advanced renal-cell carcinoma (aRCC) but can increase costs. This study compares the efficacy, safety and cost-effectiveness of ICIs for newly diagnosed aRCC patients in the first-line setting. METHODS: Trials evaluating ICI regimens as first-line treatment for newly diagnosed aRCC were searched and included. A network meta-analysis (NMA) was conducted, and a cost-effectiveness analysis was performed from the US payer's perspective. The key outcomes were overall survival (OS) and progression-free survival (PFS) in the NMA, and quality-adjusted life years (QALYs), costs and the incremental cost-effectiveness ratio (ICER) in the cost-effectiveness analysis. RESULTS: Four randomized controlled trials (RCTs) involving 3758 patients receiving first-line ICIs treatment were analyzed. The NMA showed that pembrolizumab plus axitinib was ranked higher than the other three ICI regimens and sunitinib in the overall population. Nivolumab plus ipilimumab and pembrolizumab plus axitinib achieved more health benefits than the other ICI regimens and sunitinib in programmed death ligand 1 (PD-L1)-positive and negative tumors, respectively. Among the four ICI regimens, only the ICERs of nivolumab plus ipilimumab over sunitinib were lower than the willingness-to-pay threshold ($150,000/QALY) in the overall and PD-L1-positive populations, and none of four ICI regimens were lower than $150,000/QALY in PD-L1-negative populations. CONCLUSIONS: The NMA and cost-effectiveness analysis revealed that nivolumab plus ipilimumab is the most favorable first-line treatment for PD-L1-positive aRCC compared with other ICI regimens and sunitinib. Pembrolizumab plus axitinib is likely to be an alternative for PD-L1-negative aRCC due to its more favorable health advantages.

Expanding Antiviral Prophylaxis During Pregnancy to Prevent Perinatal Hepatitis B Virus Infection: A Cost-effectiveness Study.

BACKGROUND: Mother-to-child transmission (MTCT) cannot be completely prevented by the administration of active-passive immunoprophylaxis in pregnant women with hepatitis B virus (HBV) DNA levels <106 copies/mL. This study will assess the economic outcomes of expanding antiviral prophylaxis in pregnant women with HBV DNA levels <106 copies/mL. METHODS: A decision model was adopted to measure the economic outcomes of expanded antiviral prophylaxis at different cutoff values of HBV DNA in HBsAg(+) pregnant women in the context of the United States and China. The model inputs, including clinical, cost, and utility data, were extracted from published studies. Sensitivity analyses were carried out to examine the uncertainty of the model outputs. Quality-adjusted life-years (QALYs) and direct medical costs were expressed over a lifetime horizon. RESULTS: Compared with standard antiviral prophylaxis at HBV DNA ≥106 copies/mL, expanded antiviral prophylaxis improved the health outcomes, and the incremental cost of expanded antiviral prophylaxis varied from $2063 in pregnant women with HBV DNA ≥105 copies/mL to $14 925 in all HBsAg(+) pregnant women per QALY gained in the United States, and from $1624 to $12 348 in China. The model outcome was considerably influenced by the discount rate, key clinical parameters related to the incidence of MTCT, and efficacy of the prophylaxis strategy. CONCLUSIONS: This study indicates that antiviral prophylaxis using tenofovir among pregnant women with HBV DNA <106 copies/mL may be a cost-effective option, and the cutoff value of the HBV DNA load for antiviral prophylaxis needs to be tailored.

New Oral Anticoagulants for Thromboprophylaxis in Patients with Cancer Receiving Chemotherapy: An Economic Evaluation in a Chinese Setting.

BACKGROUND AND OBJECTIVE: Recent trials showed that thromboprophylaxis with new oral anticoagulants (NOACs) is effective and safe in patients with cancer initiating chemotherapy. However, the cost effectiveness of NOACs is unknown. The objective of this study was to compare the cost effectiveness of preventing venous thromboembolism with NOACs with no thromboprophylaxis for patients with cancer initiating systemic chemotherapy from the perspective of the Chinese healthcare system. METHODS: A decision analytical model consisting of both acute and chronic venous thromboembolism complications was used to assess the cost effectiveness of thromboprophylaxis with NOACs vs no thromboprophylaxis. The key clinical data were derived from the CASSINI and AVERT trials. Costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios (ICERs) were calculated for the two strategies. Scenario and sensitivity analyses were performed. RESULTS: Compared with no thromboprophylaxis, NOACs gained 0.072 QALY at an incremental cost of $US930, leading to an ICER of 12,919/QALY in patients with Khorana scores ≥ 2 by pooling the data from the CASSINI and AVERT trials. Among patients confirmed with no deep-vein thrombosis before thromboprophylaxis (the CASSINI trial) and patients without deep-vein thrombosis screening before thromboprophylaxis (the AVERT trial), the ICERs were $70,897/QALY and $87,204/QALY, respectively. The probability of NOACs being cost effective was 42% at a willingness to pay of $10,276/QALY. The ICER was sensitive to the relative risks of death and asymptomatic venous thromboembolism between NOACs and no thromboprophylaxis and the cost of NOACs. CONCLUSIONS: Thromboprophylaxis with NOACs is not likely to be cost effective in patients initiating chemotherapy in the Chinese context. The decision about thromboprophylaxis should be tailored based on the survival of patients with cancer, the risks of venous thromboembolism, and major bleeding.

Economic burden of patients with advanced non-small-cell lung cancer receiving nivolumab versus chemotherapy in China.

Aim: As new treatment patterns are gradually being used in patients with non-small-cell lung cancer, it is necessary to have a better understanding of real-world data on clinical practices and their potential impact on healthcare resource utilization (HCRU). Patients & methods: A retrospective observational study was conducted with electronic medical records from Shanghai Chest Hospital. Hospitalized patients treated with nivolumab or second-line chemotherapy were included. Results: A total of 296 patients were included in this study, of whom 187 were treated with nivolumab. About 74.33% received nivolumab monotherapy at different doses. The mean cost of nivolumab was $3334.14 (±86.69). Nivolumab decreased inpatient days to 1.9545 days with a more stable cost and HCRU per cycle. Conclusion: Nivolumab is expensive but it reduces other HCRU.

The Differences in the Safety and Tolerability of Immune Checkpoint Inhibitors as Treatment for Non-Small Cell Lung Cancer and Melanoma: Network Meta-Analysis and Systematic Review.

Background: Immune checkpoint inhibitors (ICIs) have evolved for the treatment of solid tumors. In addition to the efficacy of ICIs for cancer, the adverse events (AEs) of ICIs are also noteworthy for gradually more extensive clinical use. Objective: To conduct a systematic review and network meta-analysis to evaluate the treatment-related AEs that occurred in clinical trials using different kinds of ICIs, to explore the differences in AEs among ICIs for treating non-small cell lung cancer (NSCLC) and melanoma, and to compare select immune-related AEs. Methods: PubMed, EMBASE, Cochrane Library, ClinicalTrials.gov, and other available sources were systematically searched for published reports up to January 1, 2019. Two reviewers independently selected reports about phase II/III randomized controlled trials to compare among ICIs and between ICIs and chemotherapy. After the bias assessment of all included trials, a Bayesian network meta-analysis was performed. The primary outcomes were any-grade and high-grade treatment-related AEs from all ICIs. The secondary outcomes were AEs in patients with NSCLC and melanoma and the presence of the select AEs pneumonitis/pneumonia and colitis. Results: Eighteen randomized controlled trials containing 11,223 patients with NSCLC or melanoma were included. A total network meta-analysis was conducted. The meta-analysis showed that atezolizumab 1,200 mg and pembrolizumab 2 mg/kg every 3 weeks were generally more tolerable than other ICIs. ICI combined with chemotherapy might suggest a higher risk of treatment-related AEs than monotherapy with a single ICI, except durvalumab and ipilimumab. In the NSCLC subgroup, pembrolizumab was associated with a higher risk of high-grade AEs than nivolumab. In addition, ICIs (nivolumab, atezolizumab, and avelumab) led to a lower risk of any/high-grade treatment-related AEs than traditional chemotherapy and ICI combination chemotherapy. However, ICIs did not present preferable safety and tolerability compared to chemotherapy in treating melanoma. Compared with chemotherapy, nivolumab, durvalumab, two ICIs, and ICI combined chemotherapy led to more pneumonitis/pneumonia. However, when treating NSCLC, different types of ICIs did not differ significantly regarding the incidence of pneumonitis/pneumonia. A combination of nivolumab and ipilimumab had the highest risk for colitis, while pembrolizumab and atezolizumab had a lower possibility than the other ICIs. Conclusion: Atezolizumab 1,200 mg and pembrolizumab 2 mg/kg every 3 weeks were ordinarily safer than other ICIs. When treating NSCLC, nivolumab had the lowest risk; when treating melanoma, pembrolizumab had the lowest toxicity.