Cost-effectiveness of pembrolizumab for previously treated MSI-H/dMMR solid tumours in the UK.

OBJECTIVES: Patients with previously treated microsatellite instability-high (MSI-H)/mismatch repair deficient (dMMR) tumours have limited chemotherapeutic treatment options. Pembrolizumab received approval from the EMA in 2022 for the treatment of colorectal, endometrial, gastric, small intestine, and biliary MSI-H/dMMR tumour types. This approval was supported by data from the KEYNOTE-164 and KEYNOTE-158 clinical trials. This study evaluated the cost-effectiveness of pembrolizumab compared with standard of care (SoC) for previously treated MSI-H/dMMR solid tumours in line with the approved EMA label from a UK healthcare payer perspective. METHODS: A multi-tumour partitioned survival model was built consisting of pre-progression, progressed disease, and dead health states. Pembrolizumab survival outcomes were extrapolated using Bayesian hierarchical models (BHMs) fitted to pooled data from KEYNOTE-164 and KEYNOTE-158. Comparator outcomes were informed by published sources. Tumour sites were modelled independently and then combined, weighted by tumour site distribution. A SoC comparator was used to formulate the overall cost-effectiveness result with pembrolizumab as the intervention. SoC comprised a weighted average of the comparators by tumour site based on market share. Drug acquisition, administration, adverse events, monitoring, subsequent treatment, end-of-life costs, and testing costs were included. Sensitivity and scenario analyses were performed, including modelling pembrolizumab efficacy using standard parametric survival models. RESULTS: Pembrolizumab, at list price, was associated with £129,469 in total costs, 8.30 LYs, and 3.88 QALYs across the pooled tumour sites. SoC was associated with £28,222 in total costs, 1.14 LYs, and 0.72 QALYs across the pooled tumour sites. This yields an incremental cost-effectiveness ratio (ICER) of £32,085 per QALY. Results were robust to sensitivity and scenario analyses. CONCLUSIONS: This model demonstrates pembrolizumab provides a valuable new alternative therapy for UK patients with MSH-H/dMMR cancer at the cost of £32,085 per QALY, with confidential discounts anticipated to improve cost-effectiveness further.

Time and productivity loss associated with immunotherapy infusions for the treatment of melanoma in the United States: a survey of health care professionals and patients.

INTRODUCTION: A new dosing schedule for the oncology immunotherapy pembrolizumab, every 6 weeks (Q6W), has been approved by the U.S. FDA, reducing the frequency of visits to infusion centers. We quantified the time spent by oncologists, nurses, patients, and caregivers per melanoma-related immunotherapy infusion visit to evaluate its potential impact. METHODS: Surveys were self-completed by 100 oncologists, 101 oncology nurses, and 100 patients with melanoma across the U.S. to quantify the time spent per infusion visit with pembrolizumab (Q3W or Q6W), nivolumab (Q2W or Q4W), or nivolumab+ipilimumab (nivolumab in combination: Q3W; nivolumab maintenance: Q2W or Q4W). Time measures included traveling, waiting, consultation, infusion, post-treatment observation, and caregiving. Respondents were also surveyed regarding the impact of the COVID-19 pandemic on infusion treatments. RESULTS: Responses deemed valid were provided by 89 oncologists, 93 nurses, and 100 patients. For each new [returning] patient treated with pembrolizumab, nivolumab or nivolumab+ipilimumab, oncologists reported to spend an average of 90 [64], 87 [60] and 101 [69] minutes per infusion visit (p-value for between-group difference = 0.300 [0.627]). For first [subsequent] treatment cycles, nurses reported spending 160 [145] average minutes per visit for nivolumab+ipilimumab, versus roughly 120 [110] for the single agents (p-value for between-group difference = 0.018 [0.022]). Patients reported to spend an average of 263, 382, and 224 minutes per visit at the center for pembrolizumab (N = 47), nivolumab (n = 34), and nivolumab+ipilimumab (n = 15) respectively (p-value for between-group difference = 0.0002). Patients also reported that their unpaid (N = 20) and paid caregivers (N = 41) spent with them an average of 966 and 333 minutes, respectively, from the day before to the day after the infusion visit. CONCLUSION: Less frequent immunotherapy infusion visits may result in substantial time savings for oncologists, nurses, patients, and caregivers.

Systematic literature review and network meta-analysis of pembrolizumab versus other interventions for previously untreated, unresectable or metastatic, MSI-high or MMR-deficient CRC.

Aim: To compare pembrolizumab with competing interventions for previously untreated, unresectable or metastatic microsatellite instability-high or mismatch repair-deficient colorectal cancer. Method: Trials were identified via a systematic literature review and synthesized using a Bayesian network meta-analysis with time-varying hazard ratios (HRs). Results: Using intention-to-treat data, HRs for overall survival were generally in favor of pembrolizumab but not statistically significant; however, statistical significance was reached versus all comparators by month 16 when accounting for crossover. Estimated HRs for progression-free survival significantly favored pembrolizumab versus all comparators by month 12. Pembrolizumab was also superior to all comparators in terms of grade ≥3 adverse events. Conclusion: These analyses suggest that pembrolizumab is a highly efficacious and safe treatment in this population.

Cost-effectiveness of pembrolizumab for the first-line treatment of patients with unresectable or metastatic MSI-H/dMMR colorectal cancer in the United States.

AIMS: Approximately, 4% of Stage IV colorectal cancers (CRC) are microsatellite instability-high (MSI-H)/deficient mismatch repair (dMMR) tumors. Patients with metastatic MSI-H/dMMR CRC receiving conventional therapies experience lower response rates and tend to have worse overall survival compared with patients with microsatellite stable (MSS)/proficient mismatch repair (pMMR) CRC. Pembrolizumab received FDA approval in 2020 for first-line treatment of Stage IV MSI-H/dMMR CRC based on significantly longer progression-free survival versus standard of care (SoC, 5-fluorouracil-based therapy with or without bevacizumab or cetuximab). This study evaluated the cost-effectiveness of pembrolizumab vs. SoC as per KEYNOTE-177 and other first-line treatments for MSI-H/dMMR CRC from a US healthcare system perspective. METHODS: A three-health-state partitioned-survival model was built using progression-free and overall survival data from KEYNOTE-177 and a network meta-analysis. Utilities were derived from KEYNOTE-177 EQ-5D-3L data. Drug acquisition, administration, AE, surgery, monitoring, subsequent treatment, and terminal care costs were included. Sensitivity and scenario analyses were performed, including utilizing a state-transition model structure and adopting a societal perspective. RESULTS: Over a lifetime time horizon, pembrolizumab and SoC were associated with total QALYs of 4.85 and 3.23, and total costs of $381,735 and $370,465, respectively, resulting in an ICER of $6,984 per QALY. QALY gains were mainly driven by extended survival with pembrolizumab. Pembrolizumab incurred higher drug acquisition costs relative to SoC but was cost-saving in terms of drug administration, AE, monitoring, subsequent treatment, and terminal care. Pembrolizumab dominated FOLFOX + panitumumab, FOLFOXIRI, and FOLFOXIRI + bevacizumab, and presented ICERs of $35,220 and $276 against XELOX and XELOX + bevacizumab. Results were robust to sensitivity and scenario analyses. CONCLUSION: Pembrolizumab is highly cost-effective for the first-line treatment of unresectable or metastatic MSI-H/dMMR CRC in the US at a willingness-to-pay threshold of $100,000/QALY.Key messagesPembrolizumab is a highly cost-effective option for the first-line treatment of patients with unresectable or metastatic MSI-H/dMMR colorectal cancer in the United States at a willingness-to-pay threshold of $100,000. Compared with the current standard of care for these patients, pembrolizumab:Increases survival due to delaying and preventing progression;Increases QALYs due to longer survival, improvement in HRQoL in the progression-free health state, and fewer Grade 3+ adverse events;Reduces costs associated with administering treatment, managing adverse events, monitoring post-progression disease, providing subsequent treatment, and providing terminal care; andReduces indirect health care costs when taking a societal perspective due to productivity gains from delaying and preventing progression and death, less frequent treatment administration and less frequent Grade 3+ adverse events.

How accurate are the longer-term projections of overall survival for cancer immunotherapy for standard versus more flexible parametric extrapolation methods?

AIMS: To assess the accuracy of standard parametric survival models, spline models, and mixture cure models (MCMs) fitted to overall survival (OS) data available at the time of submission in the NICE HTA process compared with data subsequently made available. METHODS: Standard parametric distributions, spline models, and MCMs were fitted to OS data presented in single technology appraisals (TAs) for immune-checkpoint inhibitors (ICIs) in cancer. For each TA, the estimated survival from the fitted models was compared with Kaplan-Meier (KM) data that were made available following the HTA submission using differences between point estimates and restricted area under the curve (AUC) at both the midpoint and the end of additional follow-up. Differences in interval AUC values (calculated for each 6-month period) were also assessed. RESULTS: Standard parametric survival models and spline models were more likely to underestimate longer-term survival, irrespective of the measure used to assess model accuracy. MCMs were more likely to overestimate survival; however, this was improved in some cases by applying an additional hazard of mortality for "statistically cured" patients. LIMITATIONS: The accuracy of the models was assessed based on much shorter OS data than the period for which extrapolation is needed, which may impact conclusions regarding the most accurate models. The most recent TAs for ICIs have not been captured. CONCLUSIONS: There are no definitive findings that unquestionably support the use of one specific extrapolation technique. Rather, each has the potential to provide accurate or inaccurate extrapolation to longer-term data in certain circumstances, but the added flexibility of more complex models can be justified for treatments, like ICIs, that have extended survival for patients across disease areas. The use of mortality adjustments for "statistically cured" patients allows decision-makers to explore more conservative scenarios in the face of high decision uncertainty.

Cost-Effectiveness of Pembrolizumab Versus Carboplatin and Paclitaxel in Patients With Unresectable or Metastatic Melanoma After First-Line Treatment in China.

OBJECTIVE: This study aimed to evaluate the cost-effectiveness of pembrolizumab compared with standard-of-care chemotherapy (paclitaxel + carboplatin [PC]) in patients with unresectable or metastatic melanoma after first-line treatment from a Chinese healthcare system perspective. METHODS: We conducted a partitioned-survival model with a 1-week cycle length and a 20-year base-case time horizon. Piecewise parametric models were fitted to KEYNOTE-006 trial data to estimate progression-free survival and overall survival for pembrolizumab, and a network meta-analysis was used to estimate the clinical outcomes for standard of care. Quality-adjusted life-years (QALYs) were calculated using EQ-5D data from KEYNOTE-006, applying Chinese-specific utility tariffs. Costs included drug acquisition, administration, adverse events, and disease management, reflecting the Chinese pricing system. Chinese-specific disease management costs were estimated based on clinical opinion on health state resource use and chemotherapy-related adverse events. Costs and outcomes were discounted at 5% annually. Multiple deterministic and probabilistic sensitivity analyses were performed to test the robustness of the results. RESULTS: In the base-case analysis, the treatment of pembrolizumab is estimated to yield 2.63 life-years (LYs) and 2.24 QALYs at an incremental cost of ¥372 316.46 versus PC. The incremental costs per LY and per QALY were ¥141 771.00 and ¥165 865.69, respectively, the latter being below a threshold of 3 times the per capita gross domestic product (ï¿¥193 932) in China, deemed as cost-effective according to the World Health Organization threshold. These findings were robust against a wide range of sensitivity analyses. CONCLUSIONS: Pembrolizumab is projected as cost-effective compared with PC in patients with unresectable or metastatic melanoma after first-line treatment in China.

Cost-effectiveness of pembrolizumab compared with chemotherapy in the US for women with previously treated deficient mismatch repair or high microsatellite instability unresectable or metastatic endometrial cancer.

AIMS: There is limited published evidence for the cost-effectiveness of treatments for unresectable or metastatic endometrial cancer (mEC). The objective of this analysis was to assess the cost-effectiveness of pembrolizumab versus chemotherapy for previously treated unresectable or mEC, in women whose tumors have deficient mismatch repair (dMMR) or high microsatellite instability (MSI-H). The analysis was carried out from a US healthcare payer perspective. MATERIALS AND METHODS: A lifetime partitioned survival model comprising three health states (progression-free, progressed disease and death) was constructed. Chemotherapy was represented by single-agent paclitaxel or doxorubicin. Overall survival, progression-free survival and time on treatment data for pembrolizumab were obtained from a Phase II clinical study that included women with previously treated dMMR/MSI-H unresectable or mEC (KEYNOTE-158, NCT02628067). Survival data for chemotherapy were obtained from a published Phase III study for previously treated advanced endometrial cancer. Costs included were drug acquisition and administration, health-state, end-of-life, and adverse event management. Costs were presented in 2019 US$. Outcomes were calculated as quality-adjusted life-years (QALYs), using EQ-5D data from KEYNOTE-158. Model results were tested extensively in deterministic and probabilistic sensitivity analyses. RESULTS: Results demonstrated that pembrolizumab is a highly cost-effective treatment option when compared with chemotherapy, with estimated deterministic and probabilistic incremental cost-effectiveness ratios (ICERs) of $58,165 and $57,668 per QALY gained, respectively. Pembrolizumab was associated with a large QALY and life-year gain per person versus chemotherapy over the model time horizon (deterministic 4.68 life year gain, 3.80 QALYs), with the majority of QALYs accrued in the progression-free health state. LIMITATIONS: The key limitation of the analysis was the lack of comparative effectiveness data for pembrolizumab versus chemotherapy. CONCLUSIONS: Pembrolizumab is a highly cost-effective treatment option when compared with chemotherapy for women with previously treated dMMR/MSI-H unresectable or mEC. Results were robust to the changes in parameters and assumptions explored.

Cost-Effectiveness of Pembrolizumab for the Adjuvant Treatment of Melanoma Patients with Lymph Node Involvement Who Have Undergone Complete Resection in Argentina.

INTRODUCTION: The KEYNOTE-054 trial demonstrated that adjuvant pembrolizumab improves recurrence-free survival in completely resected stage III melanoma versus watchful waiting (hazard ratio [HR] = 0.57; 98.4% confidence interval [CI], 0.43-0.74). We evaluated the cost-effectiveness of pembrolizumab in Argentina, where watchful waiting is still widely used among these patients despite the high risk of recurrence with surgery alone. METHODS: A four-health state model was used (recurrence-free, locoregional recurrence [LR], distant metastases [DM], death). Lifetime medical costs to payers (72.08 Argentine pesos [AR$] = 1.00 U.S. dollar [USD]) and outcomes (3% annual discount) were assessed, together with incremental cost-effectiveness ratios (ICERs). First and LR→DM recurrences were modeled using KEYNOTE-054 and real-world data, respectively. No benefits of adjuvant treatment were assumed post-progression. Pre-DM and post-DM mortality was based on KEYNOTE-054 and on a network meta-analysis of advanced treatments expected in each arm, respectively. Utilities were derived from KEYNOTE-054 Euro-QoL data using an Argentinian algorithm, and from the literature. Public ex-factory drug prices were used. RESULTS: Patients in the pembrolizumab and the watchful waiting arms accrued 8.78 and 5.83 quality-adjusted life-years (QALYs), 9.91 and 6.98 life-years, and costs of AR$12,698,595 (176,174 USD) and AR$11,967,717 (166,034 USD), respectively. The proportion of life-years accrued that were recurrence-free was 80.8% and 56.9% in the pembrolizumab and the watchful waiting arms, respectively. Pembrolizumab patients gained 2.94 life-years and 2.96 QALYs versus watchful waiting; the ICER per QALY was AR$247,094 (3428 USD). Recurrence rates and advanced melanoma treatments were the key drivers of the ICER. At a threshold of AR$1,445,325 (29,935 USD) per QALY, pembrolizumab had an 83.5% probability of being cost-effective versus watchful waiting. CONCLUSIONS: Adjuvant pembrolizumab after complete resection of melanoma with node involvement is highly cost-effective relative to watchful waiting in Argentina, across disease stage subgroups and BRAF mutational status. This strongly supports its coverage and reimbursement across the entire health system.

An Economic Evaluation of Pembrolizumab Versus Other Adjuvant Treatment Strategies for Resected High-Risk Stage III Melanoma in the USA.

BACKGROUND AND OBJECTIVE: Over the past 5 years, adjuvant treatment options for surgically resected stage III melanoma have expanded with the introduction of several novel immune checkpoint inhibitors and targeted therapies. Pembrolizumab, a programmed cell death protein 1 inhibitor, received US Food and Drug Administration approval in 2019 for resected high-risk stage III melanoma based on significantly longer recurrence-free survival versus placebo. This study evaluated the cost-effectiveness of pembrolizumab versus other adjuvant treatment strategies for resected high-risk stage III melanoma from a US health system perspective. METHODS: A Markov cohort-level model with four states (recurrence-free, locoregional recurrence, distant metastases, death) estimated costs and quality-adjusted life-years (QALYs) for pembrolizumab versus routine observation and other adjuvant comparators: ipilimumab in the overall population; and dabrafenib + trametinib in the BRAF-mutation positive (BRAF+) subgroup. Transition probabilities starting from recurrence-free were estimated through parametric multi-state modeling based on phase 3 KEYNOTE-054 (NCT02362594) trial data for pembrolizumab and observation, and network meta-analyses for other comparators. Post-recurrence transitions were modeled based on electronic medical records data and trials in advanced/metastatic melanoma. Utilities were derived using quality-of-life data from KEYNOTE-054 and literature. Costs of treatment, adverse events, disease management, and terminal care were included. RESULTS: Over a lifetime, pembrolizumab, ipilimumab, and observation were associated with QALYs of 9.24, 7.09, and 5.95 and total costs of $511,290, $992,721, and $461,422, respectively (2019 US dollars). Pembrolizumab was thus dominant (less costly, more effective) versus ipilimumab, with an incremental cost-effectiveness ratio of $15,155/QALY versus observation. In the BRAF+ subgroup, pembrolizumab dominated dabrafenib + trametinib and observation, decreasing costs by $62,776 and $11,250 and increasing QALYs by 0.93 and 3.10 versus these comparators, respectively. Results were robust in deterministic and probabilistic sensitivity analyses. CONCLUSIONS: As adjuvant treatment for resected stage III melanoma, pembrolizumab was found to be dominant and therefore cost-effective compared with the active comparators ipilimumab and dabrafenib + trametinib. Pembrolizumab increased costs relative to observation in the overall population, with sufficient incremental benefit to be considered cost-effective based on typical willingness-to-pay thresholds.

Cost-effectiveness analysis of pembrolizumab compared to standard of care as first line treatment for patients with advanced melanoma in Hong Kong.

BACKGROUND: Pembrolizumab has been shown to improve overall survival (OS) and progression free survival (PFS) compared to ipilimumab in patients with ipilimumab-naïve advanced melanoma; however, there are no published data on the cost-effectiveness for pembrolizumab compared to standard-of-care treatments currently used in Hong Kong for advanced melanoma. METHODS: A partitioned-survival model based on data from a recent randomized phase 3 study (KEYNOTE-006) and meta-analysis was used to derive time in PFS, OS, and post-progression survival for pembrolizumab and chemotherapy, such as dacarbazine (DTIC), temozolomide (TMZ), and the paclitaxel-carboplatin combination (PC). A combination of clinical trial data, published data, results of meta-analysis, and melanoma registry data was used to extrapolate PFS and OS curves. The base-case time horizon for the model was 30 years with costs and health outcomes discounted at a rate of 5% per year. Individual patient level data on utilities and frequencies of adverse events were obtained from the final analysis of KEYNOTE-006 (cut-off date: 3-Dec-15) for pembrolizumab. Cost data included drug acquisition, treatment administration, adverse event management, and clinical management of advanced melanoma. The distribution of patient weight from the Hong Kong population was applied to calculate the drug costs. Analyses were performed from a payer's perspective. The incremental cost effectiveness ratio (ICER) expressed as cost in US Dollars (USD) per quality-adjusted life years (QALYs) was the main outcome. RESULTS: In base-case scenario, the ICER for pembrolizumab as a first-line treatment for advanced melanoma was USD49,232 compared to DTIC, with the ICER values lower than cost-effectiveness threshold in Hong Kong. Results comparing pembrolizumab to TMZ and to PC were similar to that when compared to DTIC. Probability sensitivity analyses showed that 99% of the simulated ICERs were below three times the Gross Domestic Product (GDP) per capita for Hong Kong (currently at $119,274//QALY threshold). In a scenario analysis comparing pembrolizumab with ipilimumab, the estimated ICER was USD8,904. CONCLUSIONS: Pembrolizumab is cost-effective relative to chemotherapy (DTIC, TMZ and PC), and highly-cost-effective compared to ipilimumab, for the first-line treatment of advanced melanoma in Hong Kong.

An indirect treatment comparison of the efficacy of pembrolizumab versus competing regimens for the adjuvant treatment of stage III melanoma.

Objective: To determine the efficacy of pembrolizumab relative to other treatments used in stage III melanoma by conducting a systematic literature review (SLR) and network meta-analysis (NMA). Methods: A SLR was conducted to identify randomized clinical trials (RCTs) evaluating approved adjuvant treatments including interferon-containing regimens, BRAF-inhibitors, and PD-L1 inhibitors in stage III melanoma patients. Relative treatment effects for recurrence-free survival (RFS) were synthesized with Bayesian NMA models that allowed for hazard ratios (HRs) to vary over time. Results: Included studies formed a connected network of evidence composed of eight trials. In high-risk stage III patients, the HR for pembrolizumab vs observation decreased significantly over time with the superiority of pembrolizumab over observation becoming statistically meaningful before 3 months. By 9 months, the HR for pembrolizumab vs observation was statistically significantly lower than the HR for most other treatments vs observation, with the exception of ipilimumab and biochemotherapy due to overlapping 95% credible intervals. In BRAF + patients, pembrolizumab was statistically significantly better than observation after 3 months. The HR for both BRAF-inhibitors vs observation increased significantly over time and pembrolizumab was statistically superior to both BRAF-inhibitors after 15 months. Conclusions: Pembrolizumab results in statistically significantly improved RFS compared to all competing regimens after 9 months, except ipilimumab and biochemotherapy, for the adjuvant treatment of stage III melanoma. However, point estimate HRs vs observation for pembrolizumab are much lower than those for ipilimumab. In BRAF + patients, the advantage of pembrolizumab versus competing interventions increases over time with respect to RFS.

Cost-effectiveness of pembrolizumab for the adjuvant treatment of resected high-risk stage III melanoma in the United States.

Aims: To evaluate the cost-effectiveness of adjuvant pembrolizumab relative to observation alone following complete resection of high-risk stage III melanoma with lymph node involvement, from a US health system perspective. Materials and methods: A Markov cohort model with four health states (recurrence-free, locoregional recurrence, distant metastases, and death) was developed to estimate costs, life-years, and quality-adjusted life-years (QALYs) associated with pembrolizumab vs observation over a lifetime (46-year) horizon. Using a parametric multi-state modeling approach, transition probabilities starting from recurrence-free were estimated based on patient-level data from KEYNOTE-054 (NCT02362594), a direct head-to-head phase 3 trial. Post-recurrence transition probabilities were informed by real-world retrospective data and clinical trials in advanced melanoma. Health state utilities and adverse event-related disutility were derived from KEYNOTE-054 trial data and published literature. Costs of drug acquisition and administration, adverse events, disease management, and terminal care were estimated in 2018 US dollars. Deterministic and probabilistic sensitivity analyses were conducted to assess robustness. Results: Over a lifetime horizon, adjuvant pembrolizumab and observation were associated with total QALYs of 9.24 and 5.95, total life-years of 10.54 and 7.15, and total costs of $489,820 and $440,431, respectively. The resulting incremental cost-effectiveness ratios (ICERs) for pembrolizumab vs observation were $15,009/QALY and $14,550/life-year. Across the range of input values and assumptions tested in deterministic sensitivity analyses, pembrolizumab ranged from being a dominant strategy to having an ICER of $57,449/QALY vs observation. The ICER was below a willingness-to-pay threshold of $100,000/QALY in 90.2% of probabilistic simulations. Limitations: Long-term extrapolation of outcomes was based on interim results from KEYNOTE-054, with a median follow-up of 15 months. Conclusions: Based on common willingness-to-pay benchmarks, pembrolizumab is highly cost-effective compared with observation alone for the adjuvant treatment of completely resected stage III melanoma in the US.

A review and validation of overall survival extrapolation in health technology assessments of cancer immunotherapy by the National Institute for Health and Care Excellence: how did the initial best estimate compare to trial data subsequently made available?

BACKGROUND: Validation of overall survival (OS) extrapolations of immune-checkpoint inhibitors (ICIs) during the National Institute for Health and Care Excellence (NICE) Single Technology Assessment (STA) process is limited due to data still maturing at the time of submission. Inaccurate extrapolation may lead to inappropriate decision-making. The availability of more mature trial data facilitates a retrospective analysis of the plausibility and validity of initial extrapolations. This study compares these extrapolations to subsequently available longer-term data. METHODS: A systematic search of completed NICE appraisals of ICIs from March 2000 to December 2017 was performed. A targeted search was also undertaken to procure published OS data from the pivotal clinical trials for each identified STA made available post-submission to NICE. Initial Kaplan-Meier curves and associated extrapolations from NICE documentation were extracted to compare the accuracy of OS projections versus the most mature data. RESULTS: The review identified 11 STAs, of which 10 provided OS data upon submission to NICE. The extrapolations undertaken considered parametric or piecewise survival models. Additional data cut-offs provided a mean of 18 months of OS beyond the end of the original data. Initial extrapolations typically under-estimated OS from the most mature data cut-off by 0.4-2.7%, depending on the choice of assessment method and use of the manufacturer- or ERG-preferred extrapolation. CONCLUSION: Long-term extrapolation of OS is required for NICE STAs based on initial immature OS data. The results of this study demonstrate that the initial OS extrapolations employed by manufacturers and ERGs generally predicted OS reasonably well when compared to more mature data (when available), although on average they appeared to underestimate OS. This review and validation shows that, while the choice of OS extrapolation is uncertain, the methods adopted are generally aligned with later-published follow-up data and appear appropriate for informing HTA decisions.

Revisión sistemática de utilidades relacionadas con la salud en España: el caso de la salud mental / Systematic review of health-related utilities in Spain: the case of mental health

Objetivo Dada la carencia de un registro de utilidades en población española para su uso en evaluaciones económicas, se desarrolló una revisión sistemática de utilidades o preferencias por estados de salud obtenidas de población española con el fin último de crear un catálogo accesible a los investigadores. En este artículo se detallan las utilidades relacionadas con la salud mental. Método Revisión sistemática de la literatura, con búsquedas en MEDLINE, CRD, Embase, PsycINFO, CINAHL, Cochrane y otras bases de datos. La estrategia de búsqueda combinó términos relacionados con utilidades y con España. Los criterios de inclusión eran población residente, afectada o no por alguna enfermedad; utilidades valoradas con cuestionarios validados en España (EQ-5D, HUI, SF-6D) o siguiendo técnicas directas (equivalencia temporal, standard gamble, escala visual analógica). Se realizó una síntesis narrativa de los artículos incluidos, detallando los resultados relacionados con problemas de salud mental. Resultados Se incluyeron 103 estudios, de los que se extrajeron 742 utilidades. Se identificaron 69 utilidades relacionadas con trastornos mentales y del comportamiento, extraídas de 12 estudios. El instrumento más empleado fue el cuestionario EQ-5D. Gran parte de los artículos excluidos evaluaba la calidad de vida, pero sin ofrecer el valor de la utilidad. Conclusiones La presente revisión añade valor al estudio de las utilidades en España mediante la recopilación de valores que puedan ser incluidos en evaluaciones económicas, permitiendo además identificar lagunas en la investigación en este campo. Los valores relacionados con la salud mental identificados se asemejan a otros informados en la literatura internacional (AU)

Objectives Currently, there is no registry of utility values for the Spanish population that could potentially be used in economic evaluations. Consequently, a systematic review of utilities or preferences for health states in the Spanish population was conducted. The results related to mental health are reported. Methods A systematic review of the literature was conducted. The main databases searched were MEDLINE, CRD, Embase, PsycINFO, CINAHL, and Cochrane. The search strategy combined terms related to utilities and Spain. The inclusion criteria comprised the resident population in Spain, whether affected by any disease or not; the reported utilities had to be evaluated through a tool validated in Spain (i.e., EQ-5D, HUI, SF-6D) and/or following accepted techniques (e.g., time trade-off, standard gamble, or the visual analog scale). A narrative synthesis of articles was undertaken and the results related to mental health summarized. Results A total of 103 articles were finally included, from which 742 utility values were extracted. Sixty-nine utility values related to mental health and behavioral disorders were extracted from 12 studies. The most widely used tool was the E5-QD questionnaire. Most of the excluded articles evaluated quality of life but did not provide an estimation of utilities. Conclusions This review adds value to research on utilities in Spain by gathering values to be included in economic evaluations, as well as by identifying research gaps in this field. The utility values related to mental health identified in this study are similar to those reported in international publications (AU)

[Systematic review of health-related utilities in Spain: the case of mental health]. / Revisión sistemática de utilidades relacionadas con la salud en España: el caso de la salud mental.

OBJECTIVES: Currently, there is no registry of utility values for the Spanish population that could potentially be used in economic evaluations. Consequently, a systematic review of utilities or preferences for health states in the Spanish population was conducted. The results related to mental health are reported. METHODS: A systematic review of the literature was conducted. The main databases searched were MEDLINE, CRD, Embase, PsycINFO, CINAHL, and Cochrane. The search strategy combined terms related to utilities and Spain. The inclusion criteria comprised the resident population in Spain, whether affected by any disease or not; the reported utilities had to be evaluated through a tool validated in Spain (i.e., EQ-5D, HUI, SF-6D) and/or following accepted techniques (e.g., time trade-off, standard gamble, or the visual analog scale). A narrative synthesis of articles was undertaken and the results related to mental health summarized. RESULTS: A total of 103 articles were finally included, from which 742 utility values were extracted. Sixty-nine utility values related to mental health and behavioral disorders were extracted from 12 studies. The most widely used tool was the E5-QD questionnaire. Most of the excluded articles evaluated quality of life but did not provide an estimation of utilities. CONCLUSIONS: This review adds value to research on utilities in Spain by gathering values to be included in economic evaluations, as well as by identifying research gaps in this field. The utility values related to mental health identified in this study are similar to those reported in international publications.

Cost-effectiveness of polysaccharide pneumococcal vaccination in people aged 65 and above in Poland.

INTRODUCTION: Invasive pneumococcal disease is associated with substantial morbidity, mortality and cost implications, which could be reduced by vaccination. AIM: To assess the cost-effectiveness of a 23-valent pneumococcal vaccine in the elderly (65 and older) in Poland. METHODS: A Markov model with a 1-year cycle length was developed, allowing up to 10 cohorts to enter the model over the lifetime horizon (35 years). In the base case, costs and benefits were assessed using the public health care payer (NFZ) perspective. The analysis included routine vaccination of all elderly and high-risk (HR) elderly versus no vaccination. The analysis assumed that the government would reimburse 50% of the vaccine price. Costs and benefits were discounted 5%, with costs expressed in 2009 Polish Zloty (PLN). Extensive sensitivity analyses were carried out. RESULTS: PPV23 vaccination targeting all elderly and HR elderly in Poland would avoid 8,935 pneumococcal infections, 2,542 hospitalisations, 671 deaths and 5,886 infections, 1,673 hospitalisations and 441 deaths respectively. The incremental cost per QALY gained would be PLN 3,382 in all elderly and PLN2,148 in HR elderly. CONCLUSION: Vaccinating adults 65 and older regardless of risk status with a 23-valent pneumococcal vaccine, is cost-effective, resulting in clinical and economic benefits including a non-negligible reduction of ambulatory doctor visits, hospitalizations and, deaths in Poland.

Psychosocial interventions for non-professional carers of people with Parkinson's disease: a systematic scoping review.

AIM: This paper is a report of a scoping review to systematically identify and collate the evidence on psychosocial interventions for non-professional carers of people with Parkinson's disease. BACKGROUND: Carers are critical to people with Parkinson's disease maintaining independent living and quality of life. Parkinson's disease imposes a challenging constellation of symptoms and no summary of effective interventions for carers and their unique support needs exists. DATA SOURCES: Thirty electronic databases were searched from their inception to July 2006, and bibliographies and specific internet sites were scanned. METHODS: Eligible studies were categorized according to design, type of economic evaluation where applicable, number of participants, country of evaluation, intervention, orientation, provider, setting, method of delivery, carer population, patient population, carer outcomes, patient outcomes and authors' conclusions. Data were extracted by one reviewer and checked by another reviewer; discrepancies were resolved through discussion or arbitration by a third reviewer. FINDINGS: Thirty studies met the inclusion criteria. Most investigated relatively unique interventions involving multiple elements; the majority were not aimed primarily at carers but were embedded in patient treatment programmes. Many were pilot studies, employing weak research designs and involving very small numbers of participants and most were not designed to assess the clinical or cost effectiveness of the intervention for the carers. CONCLUSION: Several interventions merit further investigation but there is currently little evidence to show which approaches are effective and cost effective in supporting carers. Future studies need to employ appropriate and rigorous research designs with adequate samples and outcome measures, and with more focus on the carer.

Duplex ultrasonography, magnetic resonance angiography, and computed tomography angiography for diagnosis and assessment of symptomatic, lower limb peripheral arterial disease: systematic review.

OBJECTIVES: To determine the diagnostic accuracy of duplex ultrasonography, magnetic resonance angiography, and computed tomography angiography, alone or in combination, for the assessment of lower limb peripheral arterial disease; to evaluate the impact of these assessment methods on management of patients and outcomes; and to evaluate the evidence regarding attitudes of patients to these technologies and summarise available data on adverse events. DESIGN: Systematic review. METHODS: Searches of 11 electronic databases (to April 2005), six journals, and reference lists of included papers for relevant studies. Two reviewers independently selected studies, extracted data, and assessed quality. Diagnostic accuracy studies were assessed for quality with the QUADAS checklist. RESULTS: 107 studies met the inclusion criteria; 58 studies provided data on diagnostic accuracy, one on outcomes in patients, four on attitudes of patients, and 44 on adverse events. Quality assessment highlighted limitations in the methods and quality of reporting. Most of the included studies reported results by arterial segment, rather than by limb or by patient, which does not account for the clustering of segments within patients, so specificities may be overstated. For the detection of stenosis of 50% or more in a lower limb vessel, contrast enhanced magnetic resonance angiography had the highest diagnostic accuracy with a median sensitivity of 95% (range 92-99.5%) and median specificity of 97% (64-99%). The results were 91% (89-99%) and 91% (83-97%) for computed tomography angiography and 88% (80-98%) and 96% (89-99%) for duplex ultrasonography. A controlled trial reported no significant differences in outcomes in patients after treatment plans based on duplex ultrasonography alone or conventional contrast angiography alone, though in 22% of patients supplementary contrast angiography was needed to form a treatment plan. The limited evidence available suggested that patients preferred magnetic resonance angiography (with or without contrast) to contrast angiography, with half expressing no preference between magnetic resonance angiography or duplex ultrasonography (among patients with no contraindications for magnetic resonance angiography, such as claustrophobia). Where data on adverse events were available, magnetic resonance angiography was associated with the highest proportion of adverse events, but these were mild. The most severe adverse events, although rare, were mainly associated with contrast angiography. CONCLUSIONS: Contrast enhanced magnetic resonance angiography seems to be more specific than computed tomography angiography (that is, better at ruling out stenosis over 50%) and more sensitive than duplex ultrasonography (that is, better at ruling in stenosis over 50%) and was generally preferred by patients over contrast angiography. Computed tomography angiography was also preferred by patients over contrast angiography; no data on patients' preference between duplex ultrasonography and contrast angiography were available. Where available, contrast enhanced magnetic resonance angiography might be a viable alternative to contrast angiography.

Economic evaluation databases as an aid to healthcare decision makers and researchers.

Economic evaluation databases have been developed to assist in setting priorities and facilitating research within the healthcare sector. This paper presents an overview of the major databases of economic evaluations currently available (HEED, NHS EED, the CEA Registry, CODECS, PEDE, EURONHEED and JEED). It describes the key features of each database and the main user groups. It also presents evidence of the value of access to economic evaluation databases, particularly for the researchers and decision makers who form their main target audience. The research available shows that both decision makers and researchers find economic evaluation databases helpful as a source of information. However, database producers may also need to better understand the requirements of their users and consider adaptations to their products.