Cost-Effectiveness of Pembrolizumab as an Adjuvant Treatment in Colombia for Melanoma Patients with Lymph Node Involvement After Complete Resection.

INTRODUCTION: The KEYNOTE-054 trial found that adjuvant treatment with pembrolizumab improved recurrence-free survival versus placebo in completely resected high-risk stage III melanoma patients. We assessed the cost-effectiveness of adjuvant pembrolizumab in Colombia compared with watchful waiting, a widely used strategy despite the high risk of recurrence with surgery alone. METHODS: A four-health state [recurrence-free (RF), locoregional recurrence (LR), distant metastases (DM), and death) Markov model was developed to assess the lifetime medical costs and outcomes (3% annual discount), along with cost-effectiveness ratios (ICERs). The transitions from the RF and LR states were modeled using KEYNOTE-054 data, and those from the DM state were modeled using data from the KEYNOTE-006 trial and a network meta-analysis of advanced treatments received after adjuvant pembrolizumab and watchful waiting. The health state utilities were derived from KEYNOTE-054 Euro-QoL data and literature. Costs are expressed in 2021 Colombian pesos (COP). RESULTS: Over a 46-year time horizon, patients on adjuvant pembrolizumab and watchful waiting were estimated to gain 9.69 and 7.56 quality-adjusted life-years (QALYs), 10.83 and 8.65 life-years (LYs), and incur costs of COP 663,595,726 and COP 563,237,206, respectively. The proportion of LYs spent in RF state was 84.63% for pembrolizumab and 72.13% for watchful waiting, yielding lower subsequent treatment, disease management, and terminal care costs for pembrolizumab. Adjuvant pembrolizumab improved survival by 2.18 LYs and 2.13 QALYs versus watchful waiting. The ICER per QALY was COP 47,081,917, primarily driven by recurrence rates and advanced melanoma treatments. The deterministic sensitivity analysis results were robust and consistent across various reasonable inputs and alternative scenarios. At a willingness-to-pay threshold of COP 69,150,201 per QALY, the probability of pembrolizumab being cost-effective was 65.70%. CONCLUSION: Pembrolizumab is cost-effective as an adjuvant treatment compared to watchful waiting among patients with high-risk stage III melanoma after complete resection in Colombia.

Cost-effectiveness of pembrolizumab for the first-line treatment of recurrent or metastatic head and neck squamous cell carcinoma in the United States.

AIMS: Pembrolizumab, as monotherapy in first-line recurrent or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) with a combined positive score (CPS) ≥1 and in combination with platinum and 5-fluorouracil (5-FU) in the overall R/M HNSCC population, received US FDA approval based on the KEYNOTE-048 trial. Using public drug prices, from a US payer perspective, we evaluated the cost-effectiveness of each pembrolizumab regimen vs. cetuximab + platinum+5-FU (EXTREME regimen, trial comparator), cisplatin + docetaxel + cetuximab (TPEx regimen), cisplatin + paclitaxel, and platinum+5-FU. METHODS: A three-state partitioned-survival model was used to project costs and outcomes over 20 years with 3% annual discounting. Progression-free and overall survival were modeled using long-term extrapolation of KEYNOTE-048 data and, for alternative comparators, data from a network meta-analysis was used. Time-on-treatment was derived from KEYNOTE-048 or approximated using network meta-analysis progression-free survival estimates. Costs included first-line and subsequent treatments, disease management, adverse events, and terminal care costs. Utilities were derived from the KEYNOTE-048 Euro-QoL five-dimension data and using a US algorithm. RESULTS: In the CPS ≥1 R/M HNSCC population, pembrolizumab monotherapy was dominant vs. EXTREME and TPEx regimens, and cost-effective (at $100,000/QALY threshold) vs. platinum+5-FU ($86,827/QALY) and cisplatin + paclitaxel ($81,473/QALY). Pembrolizumab combination therapy in the overall R/M HNSCC population was dominant vs. TPEx regimen, and cost-effective vs. EXTREME regimen ($1769/QALY), platinum+5-FU ($81,989/QALY), and cisplatin + paclitaxel ($89,505/QALY). Sensitivity analyses showed a high cost-effectiveness probability for pembrolizumab at the $100,000/QALY threshold. CONCLUSIONS: First-line pembrolizumab monotherapy in patients with CPS ≥1, and pembrolizumab combination therapy in the overall R/M HNSCC population is cost-effective from the perspective of the US payers.

Cost Effectiveness of PD-L1-Based Test-and-Treat Strategy with Pembrolizumab as the First-Line Treatment for Metastatic NSCLC in Hong Kong.

BACKGROUND: Pembrolizumab, a monoclonal antibody against programmed death ligand 1 (PD-L1), is approved by several regulatory agencies for first-line treatment of metastatic non-small-cell lung cancer (NSCLC) with a PD-L1 tumor proportion score (TPS) ≥ 50% and no epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase genomic tumor aberrations. This study was conducted from the perspective of the Hospital Authority in Hong Kong and aimed to evaluate the cost effectiveness of a biomarker (PD-L1) test-and-treat strategy (BTS), in which patients with a TPS ≥ 50% received pembrolizumab and other patients received platinum doublet chemotherapy versus all patients receiving platinum doublet chemotherapy. METHODS: The model used a partitioned survival approach to estimate the incremental cost-effectiveness ratio (ICER) expressed as the cost per quality-adjusted life-year (QALY) gained. The clinical efficacy, utility and safety data were derived from the KN024 trial. Costs and health outcomes were projected over a 10-year time horizon and discounted at 3% per year. Costs for drug acquisition, PD-L1 testing, drug administration and disease management were used. Sensitivity analyses were conducted to evaluate the robustness of results. RESULTS: The BTS approach led to an increase of 0.29 QALYs at an additional cost of Hong Kong dollars (HK$) 249,077 (US$31,933) compared with platinum doublet chemotherapy, resulting in an ICER of HK$865,189 (US$110,922) per QALY gained. This is lower than the World Health Organization cost-effectiveness threshold of three times the 2016 gross domestic product (GDP) per capita for Hong Kong of HK$1017,819 (US$130,490). Probabilistic sensitivity analyses showed a 59.4% chance that the ICER would be below this threshold. CONCLUSION: First-line treatment with pembrolizumab in a BTS to identify patients with NSCLC with PD-L1 TPS ≥ 50% can be considered cost effective in Hong Kong compared with platinum doublet chemotherapy based on a three-times GDP per capita threshold. However, local data on clinical efficacy and safety were not available to estimate overall survival (OS) and progression-free survival (PFS) specific to patients with NSCLC in Hong Kong. Further, uncertainty is inherent in the survival projections/extrapolation of PFS and OS beyond the trial period, and future research may help to further inform these parameters.

Comparison of costs and outcomes of dapagliflozin with other glucose-lowering therapy classes added to metformin using a short-term cost-effectiveness model in the US setting.

OBJECTIVE: To compare 1-year costs and benefits of dapagliflozin (DAPA), a sodium-glucose cotransporter-2 (SGLT-2) inhibitor, with those of other treatments for type 2 diabetes (T2D), such as glucagon-like peptide-1 receptor agonists (GLP-1RAs), sulfonylureas (SUs), thiazolidinediones (TZDs), and dipeptidyl peptidase-4 inhibitors (DPP-4i), all combined with metformin. METHODS: A short-term decision-analytic model with a 1-year time horizon was developed from a payer's perspective in the United States setting. Costs and benefits associated with four clinical end-points (glycated hemoglobin [A1C], body weight, systolic blood pressure [SBP], and risk of hypoglycemia) were evaluated in the analysis. The impact of DAPA and other glucose-lowering therapy classes on these clinical end-points was estimated from a network meta-analysis (NMA). Data for costs and quality-adjusted life-years (QALYs) associated with a per-unit change in these clinical end-points were taken from published literature. Drug prices were taken from an annual wholesale price list. All costs were inflation-adjusted to December 2016 costs using the medical care component of the consumer price index. Total costs (both medical and drug costs), total QALYs, and incremental cost-effectiveness ratios (ICERs) were estimated. Sensitivity analyses (SA) were performed to explore uncertainty in the inputs. To assess face validity, results from the short-term model were compared with long-term models published for these drugs. RESULTS: The total annual medical cost for DAPA was less than that for GLP-1RA ($186 less), DPP-4i ($1,142 less), SU ($2,474 less), and TZD ($1,640 less). Treatment with DAPA resulted in an average QALY gain of 0.0107, 0.0587, 0.1137, and 0.0715 per treated patient when compared with GLP-1RA, DPP-4i, SU, and TZD, respectively. ICERs for DAPA vs SU and TZD were $19,005 and $25,835, respectively. DAPA was a cost-saving option when compared with GLP-1RAs and DPP-4is. Among all four clinical end-points, change in weight had the greatest impact on total annual costs and ICERS. Sensitivity analysis showed that results were robust, and results from the short-term model were found to be similar to those of published long-term models. CONCLUSION: This analysis showed that DAPA was cost-saving compared with GLP-1RA and DPP-4i, and cost-effective compared with SU and TZD in the US setting over 1 year. Furthermore, the results suggest that, among the four composite clinical end-points, change in weight and SBP had an impact on cost-effectiveness results.

Estimating the prevalence of generalized and partial lipodystrophy: findings and challenges.

BACKGROUND: Lipodystrophy (LD; non-human immunodeficiency virus [HIV]-associated) syndromes are a rare body of disorders for which true prevalence is unknown. Prevalence estimates of rare diseases are important to increase awareness and financial resources. Current qualitative and quantitative estimates of LD prevalence range from ~0.1 to 90 cases/million. We demonstrate an approach to quantitatively estimate LD prevalence (all, generalized, and partial) through a search of 5 electronic medical record (EMR) databases and 4 literature searches. METHODS: EMR and literature searches were conducted from 2012 to 2014. For the EMR database searches (Quintiles, IMS LifeLink, General Electric Healthcare, and Humedica EMR), LD cases were identified by the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) code 272.6 (United Kingdom General Practice Research Database used other diagnostic codes to identify LD) plus additional LD-associated clinical characteristics (patients with HIV or documented HIV treatment were excluded). Expert adjudication of cases was used for the Quintiles database only. Literature searches (PubMed and EMBASE) were conducted for each of the 4 major LD subtypes. Prevalence estimates were determined by extrapolating the total number of cases identified for each search to the database population (EMR search) and European population (literature search). RESULTS: The prevalence range of all LD across all EMR databases was 1.3-4.7 cases/million. For the adjudicated Quintiles search, the estimated prevalence of diagnosed LD was 3.07 cases/million (95% confidence interval [CI], 2.30-4.02), 0.23 cases/million (95% CI, 0.06-0.59) and 2.84 cases/million (95% CI, 2.10-3.75) for generalized lipodystrophy (GL) and partial lipodystrophy (PL), respectively. For all literature searches, the prevalence of all LD in Europe was 2.63 cases/million (0.96 and 1.67 cases/million for GL and PL, respectively). CONCLUSION: LD prevalence estimates are at the lower range of previously established numbers, confirming that LD is an ultra-rare disease. The establishment of diagnostic criteria and coding specific to the 4 major LD subtypes and future studies/patient registries are needed to further refine our estimates.

Public Health Impact and Cost-Effectiveness of Hepatitis A Vaccination in the United States: A Disease Transmission Dynamic Modeling Approach.

OBJECTIVE: To assess the population-level impact and cost-effectiveness of hepatitis A vaccination programs in the United States. METHODS: We developed an age-structured population model of hepatitis A transmission dynamics to evaluate two policies of administering a two-dose hepatitis A vaccine to children aged 12 to 18 months: 1) universal routine vaccination as recommended by the Advisory Committee on Immunization Practices in 2006 and 2) Advisory Committee on Immunization Practices's previous regional policy of routine vaccination of children living in states with high hepatitis A incidence. Inputs were obtained from the published literature, public sources, and clinical trial data. The model was fitted to hepatitis A seroprevalence (National Health and Nutrition Examination Survey II and III) and reported incidence from the National Notifiable Diseases Surveillance System (1980-1995). We used a societal perspective and projected costs (in 2013 US $), quality-adjusted life-years, incremental cost-effectiveness ratio, and other outcomes over the period 2006 to 2106. RESULTS: On average, universal routine hepatitis A vaccination prevented 259,776 additional infections, 167,094 outpatient visits, 4781 hospitalizations, and 228 deaths annually. Compared with the regional vaccination policy, universal routine hepatitis A vaccination was cost saving. In scenario analysis, universal vaccination prevented 94,957 infections, 46,179 outpatient visits, 1286 hospitalizations, and 15 deaths annually and had an incremental cost-effectiveness ratio of $21,223/quality-adjusted life-year when herd protection was ignored. CONCLUSIONS: Our model predicted that universal childhood hepatitis A vaccination led to significant reductions in hepatitis A mortality and morbidity. Consequently, universal vaccination was cost saving compared with a regional vaccination policy. Herd protection effects of hepatitis A vaccination programs had a significant impact on hepatitis A mortality, morbidity, and cost-effectiveness ratios.

Cost-effectiveness of a pentavalent rotavirus vaccine in Japan.

OBJECTIVE: To evaluate the impact of universal vaccination with a pentavalent rotavirus vaccine (RV5) on the healthcare burden and costs associated with rotavirus gastroenteritis (RGE) in Japan. METHODS: The model included a hypothetical cohort of 1,091,156 children followed for their first 5 years of life. In the absence of universal vaccination, there were 19 deaths, 78,000 hospitalizations, and 678,000 outpatient visits due to RGE. The efficacy of RV5 is based on international clinical trial data, which was similar to the efficacy observed in clinical trials conducted in Japan. The primary outcome measure is the cost per quality-adjusted-life-year (QALY) gained. In the base case, the QALY loss per 1000 RGE episodes included 2.2 for children and 1.8 per parent. RESULTS: Universal vaccination is projected to reduce hospitalizations by 92%, outpatient visits by 74%, and work-loss days by 73%. For the base case analysis, the total vaccination cost was ¥26 billion. The estimated reduction in medical costs was ¥16 billion. Of 2500 QALYs gained with the vaccination program, approximately half are directly attributed to the child. In the base case analysis, the incremental cost-effectiveness ratio (ICER) for vaccination vs. no vaccination is ¥4 million and ¥2 million per quality-adjusted life year (QALY) gained from the healthcare payer and societal perspectives, respectively. The ICERs are ¥8 million and ¥4 million if parental disutilities are excluded. KEY LIMITATION: The QALY decrements for children and parents were evaluated using different instruments, and the QALY decrements do not vary based on episode severity. Given the interdependence between children and their parents, excluding parental disutilities may under-estimate the impact of RGE. CONCLUSION: Universal vaccination with RV5 in Japan is projected to have a substantial public health impact and may be cost-effective from both the payer and societal perspectives if parental disutilities are included in the cost-effectiveness ratios.

Cost-effectiveness of stockpiling 23-valent pneumococcal polysaccharide vaccine to prevent secondary pneumococcal infections among a high-risk population in the United States during an influenza pandemic.

BACKGROUND: Secondary bacterial infections (especially pneumococcal infections) were a major cause of death during prior influenza pandemics. One strategy to prevent pneumococcal infections in adults during a future pandemic is to stockpile 23-valent pneumococcal polysaccharide vaccine (PPSV23). Stockpiling a pneumococcal vaccine can ensure that it is available when needed most-that is, at the onset of a pandemic. OBJECTIVE: The purpose of this article was to project the health and economic impact of stockpiling PPSV23 to prevent secondary pneumococcal infections among high-risk adults aged 18 to 64 years during an influenza pandemic within the United States. METHODS: A cost-effectiveness model was developed to evaluate the health and economic effects of stockpiling PPSV23 versus not stockpiling this vaccine for preventing secondary pneumococcal infections among 20 million high-risk US adults aged 18 to 64 years during an influenza pandemic. The model was used to project the number of pneumococcal cases, hospitalizations, deaths, and days of work loss averted. Three health outcomes (deaths, hospitalizations, and outpatient care) were estimated from secondary pneumococcal infections. To assess the overall effectiveness of the different strategies, the quality-adjusted life-year (QALY) was used as a measure of these 3 health outcomes. The results are presented for 3 scenarios based on the pandemic severity and anticipated prepandemic influenza vaccine availability: base case, more-severe case, and less-severe case. RESULTS: In the base-case scenario, vaccinating 20 million high-risk adults with PPSV23 avoided 2858 deaths, 878 hospitalizations, 41,881 pneumococcal pneumonia cases, and 232,891 days of work loss during a pandemic. Under the more-severe case scenario, vaccination avoided 21,921 deaths, 10,280 hospitalizations, 70,345 pneumococcal cases, and approximately 1.12 million days of work loss. Under the less-severe case scenario, pneumococcal vaccination avoided 715 deaths, 219 hospitalizations, 10,470 pneumococcal cases, and 58,235 days of work loss. The incremental cost-effectiveness ratio for stockpiling PPSV23 versus no stockpiling for the base-case and less-severe case scenarios was $39,946 and $198,653 per QALY, respectively. For the more-severe case scenario, stockpiling PPSV23 was cost saving. Probabilistic sensitivity analyses found that the range of incremental cost-effectiveness ratio values was broad due to the large uncertainty regarding the timing and impact of the next pandemic. In addition, the shelf life of PPSV23 and stockpile management substantially influenced the cost-effectiveness ratio. CONCLUSIONS: For severe pandemics or pandemics in which prepandemic influenza vaccine is unavailable, stockpiling of PPSV23 can be a cost-effective strategy for reducing the health and economic burden associated with secondary pneumococcal infections in a high-risk US population. However, for a mildly severe pandemic in which prepandemic influenza vaccine is available, stockpiling of PPSV23 may not be cost-effective.

Estimating the risk of rabies transmission to humans in the U.S.: a Delphi analysis.

BACKGROUND: In the United States, the risk of rabies transmission to humans in most situations of possible exposure is unknown. Controlled studies on rabies are clearly not possible. Thus, the limited data on risk has led to the frequent administration of rabies post-exposure prophylaxis (PEP), often in inappropriate circumstances. METHODS: We used the Delphi method to obtain an expert group consensus estimate of the risk of rabies transmission to humans in seven scenarios of potential rabies exposure. We also surveyed and discussed the merits of recommending rabies PEP for each scenario. RESULTS: The median risk of rabies transmission without rabies PEP for a bite exposure by a skunk, bat, cat, and dog was estimated to be 0.05, 0.001, 0.001, and 0.00001, respectively. Rabies PEP was unanimously recommended in these scenarios. However, rabies PEP was overwhelmingly not recommended for non-bite exposures (e.g. dog licking hand but unavailable for subsequent testing), estimated to have less than 1 in 1,000,000 (0.000001) risk of transmission. CONCLUSIONS: Our results suggest that there are many common situations in which the risk of rabies transmission is so low that rabies PEP should not be recommended. These risk estimates also provide a key parameter for cost-effective models of human rabies prevention and can be used to educate health professionals about situation-specific administration of rabies PEP.

Estimates of US influenza-associated deaths made using four different methods.

BACKGROUND: A wide range of methods have been used for estimating influenza-associated deaths in temperate countries. Direct comparisons of estimates produced by using different models with US mortality data have not been published. OBJECTIVE: Compare estimates of US influenza-associated deaths made by using four models and summarize strengths and weaknesses of each model. METHODS: US mortality data from the 1972-1973 through 2002-2003 respiratory seasons and World Health Organization influenza surveillance data were used to estimate influenza-associated respiratory and circulatory deaths. Four models were used: (i) rate-difference (using peri-season or summer-season baselines), (ii) Serfling least squares cyclical regression, (iii) Serfling-Poisson regression, (iv) and autoregressive integrated moving average models. RESULTS: Annual estimates of influenza-associated deaths made using each model were similar and positively correlated, except for estimates from the summer-season rate-difference model, which were consistently higher. From the 1976/1977 through the 2002/2003 seasons the, the Poisson regression models estimated that an annual average of 25,470 [95% confidence interval (CI) 19,781-31,159] influenza-associated respiratory and circulatory deaths [9.9 deaths per 100,000 (95% CI 7.9-11.9)], while peri-season rate-difference models using a 15% threshold estimated an annual average of 22,454 (95% CI 16,189-28,719) deaths [8.6 deaths per 100,000 (95% CI 6.4-10.9)]. CONCLUSIONS: Estimates of influenza-associated mortality were of similar magnitude. Poisson regression models permit the estimation of deaths associated with influenza A and B, but require robust viral surveillance data. By contrast, simple peri-season rate-difference models may prove useful for estimating mortality in countries with sparse viral surveillance data or complex influenza seasonality.

Cost effectiveness of rabies post exposure prophylaxis in the United States.

There is growing concern in the United States about the excessive use of rabies post exposure prophylaxis (PEP) treatment. In this paper we have estimated the cost effectiveness of rabies PEP treatment under various scenarios of rabies transmission. When the risk of a patient getting rabies is deemed greater than 0.7%, then giving PEP will be cost saving (societal perspective). For lower risks of transmission, cost effectiveness estimates ranged from approximately $500,000 per life saved to $billions. The uncertainty caused by the wide range of cost effectiveness can only be resolved through analysis of data describing rabies transmission risk in a variety of scenarios.

Human rabies prevention--United States, 2008: recommendations of the Advisory Committee on Immunization Practices.

These recommendations of the Advisory Committee on Immunization Practices (ACIP) update the previous recommendations on human rabies prevention (CDC. Human rabies prevention--United States, 1999: recommendations of the Advisory Committee on Immunization Practices. MMWR 1999;48 [No. RR-1]) and reflect the status of rabies and antirabies biologics in the United States. This statement 1) provides updated information on human and animal rabies epidemiology; 2) summarizes the evidence regarding the effectiveness/efficacy, immunogenicity, and safety of rabies biologics; 3) presents new information on the cost-effectiveness of rabies postexposure prophylaxis; 4) presents recommendations for rabies postexposure and pre-exposure prophylaxis; and 5) presents information regarding treatment considerations for human rabies patients. These recommendations involve no substantial changes to the recommended approach for rabies postexposure or pre-exposure prophylaxis. ACIP recommends that prophylaxis for the prevention of rabies in humans exposed to rabies virus should include prompt and thorough wound cleansing followed by passive rabies immunization with human rabies immune globulin (HRIG) and vaccination with a cell culture rabies vaccine. For persons who have never been vaccinated against rabies, postexposure antirabies vaccination should always include administration of both passive antibody (HRIG) and vaccine (human diploid cell vaccine [HDCV] or purified chick embryo cell vaccine [PCECV]). Persons who have ever previously received complete vaccination regimens (pre-exposure or postexposure) with a cell culture vaccine or persons who have been vaccinated with other types of vaccines and have previously had a documented rabies virus neutralizing antibody titer should receive only 2 doses of vaccine: one on day 0 (as soon as the exposure is recognized and administration of vaccine can be arranged) and the second on day 3. HRIG is administered only once (i.e., at the beginning of antirabies prophylaxis) to previously unvaccinated persons to provide immediate, passive, rabies virus neutralizing antibody coverage until the patient responds to HDCV or PCECV by actively producing antibodies. A regimen of 5 1-mL doses of HDCV or PCECV should be administered intramuscularly to previously unvaccinated persons. The first dose of the 5-dose course should be administered as soon as possible after exposure (day 0). Additional doses should then be administered on days 3, 7, 14, and 28 after the first vaccination. Rabies pre-exposure vaccination should include three 1.0-mL injections of HDCV or PCECV administered intramuscularly (one injection per day on days 0, 7, and 21 or 28). Modifications were made to the language of the guidelines to clarify the recommendations and better specify the situations in which rabies post- and pre-exposure prophylaxis should be administered. No new rabies biologics are presented, and no changes were made to the vaccination schedules. However, rabies vaccine adsorbed (RVA, Bioport Corporation) is no longer available for rabies postexposure or pre-exposure prophylaxis, and intradermal pre-exposure prophylaxis is no longer recommended because it is not available in the United States.