Health State Transition Research Articles

Health Utility during the First Two Years of Treatment of Hematological Malignancies

BackgroundThere are limited patient reported outcomes for acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) due to relatively low incidence rates and disease severity. Patient reported outcomes on health utility, a measure of quality of life weighted to the preferences of the general population, are however required for economic evaluation of interventions to diagnose and treat the diseases. This study was designed to report health utility outcomes from patients during their treatment for AML and MDS, for the first time. We sought to use the infrastructure of a multicentre study to report these outcomes in an otherwise inaccessible patient population and enable more accurate economic models.MethodsFollowing institutional research ethics board approval at six recruiting study centres across Canada, the Euroqol five dimensions (EQ5D) health utility instrument and socio-demographic questionnaires were administered by telephone or in person to eligible participants in a national clinical study (NCT01685619). These data were linked to the treatment outcomes and health state transitions of each participant during their treatment of AML or MDS. A longitudinal analysis of treatment effects and cross-sectional regression analyses were undertaken for data collected at four, quarterly time points over the first year following diagnosis, and two semi-annual points over the second year. We defined health utility for specific economic health states and the co-varying impacts from socio-demographic characteristics and treatment-related impacts.ResultsAt least one quality of life questionnaire was returned for 131 (96%) of the eligible patients who participated in the study. Response rates were greater than 60% at each of the scheduled time points. The median overall survival (468 days; 95% CI: 353-660) was reached over the 24 month term of follow-up. The most preferred health states involved greater than 12 months of survival (health utility > 0.78); the least preferred health states were reported for failed treatments and an initial AML diagnosis (health utility < 0.63). There were no significant differences found among utility outcomes that could be related to consolidation modality or remission induction intent. AML patients with 24 months of survival gained 0.037 more quality adjusted life years (QALYs) than MDS patients with equivalent survival time. An ordinary least squares regression model on the cross-sectional data suggests that having an MDS diagnosis was associated with a better short-term health utility while long term outcomes were greater for patients who survived 24 months after being diagnosed with AML (p<0.1).ConclusionsThis report on health utility outcomes was made possible only by collaboration with health economists and the infrastructure of a multicentre clinical study. The data suggest that survivors following 24 months of treatment for AML gained more QALYs than the survivors of MDS. The findings warrant further investigation due to the suggestion of equivalent health utility between treatments and to further validate the use of the EQ5D instrument in this disease area. DisclosuresSavoie:Jazz: Consultancy; Lundbeck: Consultancy; Amgen: Consultancy; BMS: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Pfizer: Consultancy; Celgene: Consultancy.

Cost-Effectiveness Analysis of Consolidation with Brentuximab Vendotin Versus Active Surveillance in Individuals with High-Risk Hodgkin Lymphoma Undergoing High Dose Chemotherapy with Stem Cell Rescue

IntroductionAlthough the majority of individuals diagnosed with Hodgkin's lymphoma (HL) are cured with first-line therapy, upwards of 20-30% of patients experience primary refractory disease or relapse after achieving remission. Autologous stem cell transplantation (ASCT) remains a curative option for R/R HL, but approximately 50% will experience HL recurrence followingASCT. A recent randomized double-blind trial (ATHERA) found post-ASCTconsolidation treatment with 16 cycles ofbrentuximabvedotin(BV) decreased the risk of HL progression compared to placebo. However, the impact of BV consolidation on overall survival, quality of life, and health care costs remains to be elucidated.MethodsWe constructed a Markov decision-analytic model from the US societal perspective to compare the costs and clinical outcomes associated with post-ASCTBV consolidation versus active surveillance with BV at time of HL progression. Patients entered our post-ASCTmodel receiving BV consolidation or active surveillance, with 4 additional 3-month health transition states used to model care until death (Figure 1). Results from theATHERAtrial informed the majority of our health state transition probabilities and our cohort characteristics.Rates of HL progression followingASCTwere extrapolated to 5 years using standard parametric modeling of reconstructed individual patient data derived from publishedATHERAresults.Our model also incorporated a number of recently published studies, including long term follow-up data of BV monotherapy in the salvage setting and separate reports supporting the use ofnivolumabfor R/R HL. All drug costs were calculated at 106% of average sales price and administrative costs were derived from the Medicare fee schedule. All future costs and benefits were discounted at 3% annually and a lifetime horizon was used to estimate cumulative healthcare costs and health utilities. Quality-adjusted utility, lifetime costs, and incremental cost-effectiveness ratios (ICERs) were calculated for each post-ASCTstrategy.ResultsReconstructed individual patient data from publishedATHERAresults was best fit using aGompertzdistribution. This parametric model predicted 5-year progression free survival to be 54% for BV consolidation compared to 43% for active surveillance. This reduction in HL progression translated intolonger overall survival (OS) for individuals receiving BV consolidation (mean [median] OS: 30.2 [36.6] vs 28.0 [29.9] years). After quality-of-life adjustments and standard future discounting, BV consolidation was associated with an improvement of 0.98 quality-adjusted-life years (QALYs) compared to active surveillance. However, the strategy of BV consolidation led to significantly higher healthcare costs ($330,833 vs $187,747), with anICERof $146,006/QALYfor BV consolidation compared to active surveillance. Model conclusions were stable on sensitivity analyses, including probabilistic sensitivity analysis where less than 5% of iterations found BV consolidation cost-effective at a level of $100,000/QALY.ConclusionsAlthough consolidation treatment with BV followingASCTappears to reduce the risk of HL recurrence and prolong survival, the strategy is associated with significant health care costs compared to active surveillance. Our analysis suggests the use of BV as consolidation therapy at current US pricing ($137/mg) is unlikely to be cost-effective at a willingness to pay of $100,000/QALY. However, if indication-specific pricing were implemented, our model estimates BV price reductions of 20% to 40% for the post-ASCTconsolidative setting would translate toICERsof $100,000/QALYand $50,000/QALY, respectively. Thus, for effective therapies such as BV, moderate reductions in current prices may produce cost-effective strategies. Ultimately, future indication-specific and value-based pricing has the potential to not only align drug prices to their value, but also continue to reward highly effective and innovative cancer therapy. [Display omitted] DisclosuresZeidan:Ariad: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria; Incyte: Consultancy, Honoraria. Gore:Celgene: Consultancy, Honoraria, Research Funding. Ma:Celgene Corporation: Consultancy. Davidoff:PhRMA: Research Funding. Huntington:Celgene: Consultancy, Honoraria; Oncosec Medical: Equity Ownership; Exelixis: Equity Ownership; Johnson & Johnson: Consultancy; Pharmacyclics: Honoraria; Geron: Equity Ownership.

Toward More Efficient Surveillance of Barrett's Esophagus: Identification and Exclusion of Patients at Low Risk of Cancer.

Endoscopic surveillance of Barrett's esophagus (BE) is probably not cost-effective. A sub-population with BE at increased risk of high-grade dysplasia (HGD) or esophageal adenocarcinoma (EAC) who could be targeted for cost-effective surveillance was sought. The outcome for BE surveillance from 2003 to 2012 in a structured program was reviewed. Incidence rates and incidence rate ratios for developing HGD or EAC were calculated. Risk stratification identified individuals who could be considered for exclusion from surveillance. A health-state transition Markov cohort model evaluated the cost-effectiveness of focusing on higher-risk individuals. During 2067 person-years of follow-up of 640 patients, 17 individuals progressed to HGD or EAC (annual IR 0.8%). Individuals with columnar-lined esophagus (CLE) ≥2cm had an annual IR of 1.2% and >8-fold increased relative risk of HGD or EAC, compared to CLE <2cm [IR-0.14% (IRR 8.6, 95% CIs 4.5-12.8)]. Limiting the surveillance cohort after the first endoscopy to individuals with CLE ≥2cm, or dysplasia, followed by a further restriction after the second endoscopy-exclusion of patients without intestinal metaplasia-removed 296 (46%) patients, and 767 (37%) person-years from surveillance. Limiting surveillance to the remaining individuals reduced the incremental cost-effectiveness ratio from US$60,858 to US$33,807 per quality-adjusted life year (QALY). Further restrictions were tested but failed to improve cost-effectiveness. Based on stratification of risk, the number of patients requiring surveillance can be reduced by at least a third. At a willingness-to-pay threshold of US$50,000 per QALY, surveillance of higher-risk individuals becomes cost-effective.

Public health impact of comprehensive hepatitis C screening and treatment in the French baby-boomer population

Objective: To estimate the public health impact of comprehensive hepatitis C virus (HCV) screening and access to all-oral, interferon (IFN)-free direct-acting antivirals (DAAs) in the French baby-boomer population (1945–1965 birth cohorts).Methods: A sequential, multi-cohort, health-state transition model was developed to assess the impact of different hepatitis C screening and treatment strategies on clinical and economic outcomes in the 1945–1965 birth cohorts. Patients newly-diagnosed with chronic HCV were projected each year from 2016 to 2036 under three screening scenarios (70% [low], 75% [intermediate], and 80% [high] HCV awareness in 2036). Healthcare costs and clinical outcomes (number of liver-related deaths, quality-adjusted life-years [QALYs], life-years [LYs] spent in sustained virologic response [SVR] or with decompensated cirrhosis, hepatocellular carcinoma, or liver transplant) were compared among five treatment strategies (no antiviral therapy; IFN + ribavirin + protease inhibitor for fibrosis stages F2–F4, IFN-based DAAs for stages F2–F4, IFN-free DAAs for stages F2–F4, and IFN-free DAAs for stages F0–F4).Results: Diagnosis of HCV genotype 1 was projected for 4,953, 6,600, and 8,368 individuals in the low, intermediate, and high screening scenarios, respectively. In the intermediate scenario, IFN-free DAAs for stages F0–F4 had a favorable cost-effectiveness profile vs IFN-based or IFN-free treatment strategies for F2–F4 and offered the greatest return on investment (0.899 LYs gained in SVR and 0.933 QALYs per €10,000 invested).Conclusion: Comprehensive HCV screening and access to all-oral, IFN-free DAAs is a cost-effective strategy that could help diminish the upcoming burden of HCV in the French baby-boomer population.

Economic evaluation of pegylated interferon plus ribavirin for treatment of chronic hepatitis C in Thailand: genotype 1 and 6.

BackgroundPegylated interferon alpha 2a, alpha 2b and ribavirin have been included to the National List of Essential Medicines (NLEM) for treatment of only chronic hepatitis C genotypes 2 and 3 in Thailand. This reimbursement policy has not covered for other genotypes of hepatitis C virus infection (HCV) especially for genotypes 1 and 6 that account for 30-50 % of all HCV infection in Thailand. Therefore, this research determined whether pegylated interferon alpha 2a or alpha 2b plus ribavirin is more cost-effective than a palliative care for treatment of HCV genotype 1 and 6 in Thailand.MethodsA cost-utility analysis using a model-based economic evaluation was conducted based on a societal perspective. A Markov model was developed to estimate costs and quality-adjusted life years (QALYs) comparing between the combination of pegylated interferon alpha 2a or alpha 2b and ribavirin with a usual palliative care for genotype 1 and 6 HCV patients. Health-state transition probabilities, virological responses, and utility values were obtained from published literatures. Direct medical and direct non-medical costs were included and retrieved from published articles and Thai Standard Cost List for Health Technology Assessment. The incremental cost-effectiveness ratio (ICER) was presented as costs in Thai baht per QALY gained.ResultsHCV treatment with pegylated interferon alpha 2a or alpha 2b plus ribavirin was dominant or cost-saving in Thailand compared to a palliative care. The ICER value was negative with lower in total costs (peg 2a- 747,718vs. peg 2b- 819,921 vs. palliative care- 1,169,121 Thai baht) and more in QALYs (peg 2a- 13.44 vs. peg 2b- 13.14 vs. palliative care- 11.63 years) both in HCV genotypes 1 and 6.ConclusionAs cost-saving results, the Subcommittee for Development of the NLEM decided to include both pegylated interferon alpha 2a and alpha 2b into the NLEM for treatment of HCV genotype 1 and 6 recently. Economic evaluation for these current drugs can be further applied to other novel medications for HCV treatment.

Cost-effectiveness of direct-acting antiviral regimen ombitasvir/paritaprevir/ritonavir in treatment-naïve and treatment-experienced patients infected with chronic hepatitis C virus genotype 1b in Japan

Objective: This study compared the cost-effectiveness of chronic hepatitis C virus (HCV) genotype 1b (GT1b) therapy ombitasvir/paritaprevir/ritonavir (OBV/PTV/r) vs daclatasvir + asunaprevir (DCV/ASV) and no treatment in patients without cirrhosis. Cost-effectiveness analyses (CEAs) that compared OBV/PTV/r against DCV/ASV and sofosbuvir/ledipasvir (SOF/LDV) in Y93H mutation-negative, GT1b patients with and without cirrhosis were also included.Methods: A health state transition model was developed to capture the natural history of HCV. A CEA over a lifetime horizon was performed from the perspective of the public healthcare payer in Japan. Costs, health utilities, and rates of disease progression were derived from published studies. Sustained virologic response (SVR) rates of OBV/PTV/r and DCV/ASV were extracted from Japanese clinical trials. Analyses were performed for treatment-naïve and -experienced patients. Alternative scenarios and input parameter uncertainty on the results were tested.Results: OBV/PTV/r exhibited superior clinical outcomes vs comparators. For OBV/PTV/r, DCV/ASV, and no treatment, the lifetime risk of decompensated cirrhosis in treatment-naïve patients without cirrhosis was 0.4%, 1.4%, and 9.2%, and hepatocellular carcinoma was 6.5%, 11.4%, and 49.9%, respectively. Quality-adjusted life years (QALYs) were higher in treatment-naïve and -experienced patients without cirrhosis treated with OBV/PTV/r (16.41 and 16.22) vs DCV/ASV (15.83 and 15.66) or no treatment (11.34 and 11.23). In treatment-naïve and -experienced patients without cirrhosis, the incremental cost-effectiveness ratios (ICERs) of OBV/PTV/r vs DCV/ASV were JPY 1,684,751/QALY and JPY 1,836,596/QALY, respectively; OBV/PTV/r was dominant compared with no treatment. In scenario analysis, including GT1b patients with and without cirrhosis who were Y93H mutation-negative, the ICER of OBV/PTV/r vs DCV/ASV was below the Japanese willingness-to-pay threshold of JPY 5 million/QALY, while the ICER of SOF/LDV vs OBV/PTV/r was above this threshold; thus, OBV/PTV/r was cost-effective.Conclusion: OBV/PTV/r appears to be a cost-effective treatment for chronic HCV GT1b infection against DCV/ASV. OBV/PTV/r dominates no treatment in patients without cirrhosis.

The Clinical and Economic Benefits of Co-Testing Versus Primary HPV Testing for Cervical Cancer Screening: A Modeling Analysis.

Background: Consensus United States cervical cancer screening guidelines recommend use of combination Pap plus human papillomavirus (HPV) testing for women aged 30 to 65 years. An HPV test was approved by the Food and Drug Administration in 2014 for primary cervical cancer screening in women age 25 years and older. Here, we present the results of clinical-economic comparisons of Pap plus HPV mRNA testing including genotyping for HPV 16/18 (co-testing) versus DNA-based primary HPV testing with HPV 16/18 genotyping and reflex cytology (HPV primary) for cervical cancer screening.Methods: A health state transition (Markov) model with 1-year cycling was developed using epidemiologic, clinical, and economic data from healthcare databases and published literature. A hypothetical cohort of one million women receiving triennial cervical cancer screening was simulated from ages 30 to 70 years. Screening strategies compared HPV primary to co-testing. Outcomes included total and incremental differences in costs, invasive cervical cancer (ICC) cases, ICC deaths, number of colposcopies, and quality-adjusted life years for cost-effectiveness calculations. Comprehensive sensitivity analyses were performed.Results: In a simulation cohort of one million 30-year-old women modeled up to age 70 years, the model predicted that screening with HPV primary testing instead of co-testing could lead to as many as 2,141 more ICC cases and 2,041 more ICC deaths. In the simulation, co-testing demonstrated a greater number of lifetime quality-adjusted life years (22,334) and yielded $39.0 million in savings compared with HPV primary, thereby conferring greater effectiveness at lower cost.Conclusions: Model results demonstrate that co-testing has the potential to provide improved clinical and economic outcomes when compared with HPV primary. While actual cost and outcome data are evaluated, these findings are relevant to U.S. healthcare payers and women's health policy advocates seeking cost-effective cervical cancer screening technologies.

Cost-benefits of incorporating levosimendan into cardiac surgery practice: German base case

Objective:To evaluate the cost-benefit of using levosimendan compared with dobutamine, in the perioperative treatment of patients undergoing cardiac surgery who require inotropic support.Methods:A two-part Markov model was designed to simulate health-state transitions of patients undergoing cardiac surgery, and estimate the short- and long-term health benefits of treatment. Hospital length of stay (LOS), mortality, medication, and adverse events were key clinical- and cost-inputs. Cost-benefits were evaluated in terms of costs and bed stays within the German healthcare system. Drug prices were calculated from the German Drug Directory (€/2014) and published literature, with a 3% annual discount rate applied. The base case analysis was for a 1-year time horizon.Results:The use of levosimendan vs dobutamine was associated with cost savings of €4787 per patient from the German hospital perspective due to reduced adverse events and shorter hospital LOS, leading to increased bed capacity and hospital revenue.Limitations:A pharmacoeconomic calculation for the specific situation of the German healthcare system that is based on international clinical trial carries a substantial risk of disregarding potentially relevant but unknown confounding factors (i.e., ICU-staffing, co-medications, standard-ICU care vs fast-tracking, etc.) that may either attenuate or increase the outcome pharmacoeconomic effects of a drug; however, since these conditions would also apply for patients treated with comparators, their net effects may not necessarily influence the conclusions.Conclusions:The use of levosimendan in patients undergoing cardiac surgery who require inotropic support appears to be cost-saving. The results of the analysis provide a strong rationale to run local clinical studies with pharmacoeconomic end-points which would allow a much more precise computation of the benefits of levosimendan.

Health state transitions among prescribed opiate patients accessing pharmacological treatment for opioid dependence in California, 2006–2010

Health state transitions among prescribed opiate patients accessing pharmacological treatment for opioid dependence in California, 2006–2010

Educational attainment and health transitions over the life course: testing the potential mechanisms.

It has been shown that higher education associates with health outcomes, but the less is known about the specific mechanisms mediating this association. We examined whether higher education would associate with long-term health transitions from childhood to adulthood and whether health behaviors, self-esteem, social support and work-related health hazards could mediate or confound this association. The participants were from a population-based sample of 3596 men and women from the Young Finns study aged 3-18 years at the beginning of the study in 1980, and who responded to repeated surveys of educational attainment and self-rated health in four study phases from 1997 to 2012. The associations were tested using multistate Markov models for the health-state transition intensities. Our results suggested that a 1-year difference in education was related to a 16% higher transition probability from mediocre to good self-rated health over the 5-year follow-up. Depressive symptoms and job strain seemed to partly mediate or confound the association, but self-esteem and social support did not. These results suggest that educational attainment is associated with good self-rated health transitions from childhood to adulthood, and multiple processes rather than a single underlying mechanism are likely to drive the educational differences in self-rated health.

The Impact of Company-Level ART Provision to a Mining Workforce in South Africa: A Cost-Benefit Analysis.

BackgroundHIV impacts heavily on the operating costs of companies in sub-Saharan Africa, with many companies now providing antiretroviral therapy (ART) programmes in the workplace. A full cost–benefit analysis of workplace ART provision has not been conducted using primary data. We developed a dynamic health-state transition model to estimate the economic impact of HIV and the cost–benefit of ART provision in a mining company in South Africa between 2003 and 2022.Methods and FindingsA dynamic health-state transition model, called the Workplace Impact Model (WIM), was parameterised with workplace data on workforce size, composition, turnover, HIV incidence, and CD4 cell count development. Bottom-up cost analyses from the employer perspective supplied data on inpatient and outpatient resource utilisation and the costs of absenteeism and replacement of sick workers. The model was fitted to workforce HIV prevalence and separation data while incorporating parameter uncertainty; univariate sensitivity analyses were used to assess the robustness of the model findings. As ART coverage increases from 10% to 97% of eligible employees, increases in survival and retention of HIV-positive employees and associated reductions in absenteeism and benefit payments lead to cost savings compared to a scenario of no treatment provision, with the annual cost of HIV to the company decreasing by 5% (90% credibility interval [CrI] 2%–8%) and the mean cost per HIV-positive employee decreasing by 14% (90% CrI 7%–19%) by 2022. This translates into an average saving of US$950,215 (90% CrI US$220,879–US$1.6 million) per year; 80% of these cost savings are due to reductions in benefit payments and inpatient care costs. Although findings are sensitive to assumptions regarding incidence and absenteeism, ART is cost-saving under considerable parameter uncertainty and in all tested scenarios, including when prevalence is reduced to 1%—except when no benefits were paid out to employees leaving the workforce and when absenteeism rates were half of what data suggested. Scaling up ART further through a universal test and treat strategy doubles savings; incorporating ART for family members reduces savings but is still marginally cost-saving compared to no treatment. Our analysis was limited to the direct cost of HIV to companies and did not examine the impact of HIV prevention policies on the miners or their families, and a few model inputs were based on limited data, though in sensitivity analysis our results were found to be robust to changes to these inputs along plausible ranges.ConclusionsWorkplace ART provision can be cost-saving for companies in high HIV prevalence settings due to reductions in healthcare costs, absenteeism, and staff turnover. Company-sponsored HIV counselling and voluntary testing with ensuing treatment of all HIV-positive employees and family members should be implemented universally at workplaces in countries with high HIV prevalence.

A cost utility analysis of simeprevir used with peginterferon + ribavirin in the management of genotype 1 hepatitis C virus infection, from the perspective of the UK National Health Service

Introduction:Triple therapy using a protease inhibitor (PI) with peginterferon and ribavirin (PR) is increasingly used in patients with chronic hepatitis C virus (HCV) infection. The most recently introduced PI, simeprevir (SMV), offers high levels of viral eradication combined with a reduced overall duration of therapy. The objective of this study was to compare the cost-effectiveness of SMV + PR vs PR alone or in combination with telaprevir (TVR) or boceprevir (BOC) in patients infected with genotype 1 HCVMethod:A cost-utility model was constructed, incorporating two phases, capturing the efficacy of therapy in an initial treatment phase, followed by a long-term post-treatment Markov phase, capturing lifetime outcomes according to whether a sustained viral response (SVR) had been achieved on treatment. Dosage regimens were based on the EMA approved label for each treatment. SVR estimates and adverse event rates were derived from a mixed treatment comparison. Baseline characteristics were drawn from an analysis of a UK HCV data-set and clinician opinion. Health state transition probabilities, utilities, and health state costs were drawn from previously published economic analyses. The model considered direct health costs only, and the perspective was that of the UK National Health Service.Results:The model yielded an ICER for SMV + PR vs PR alone of £9725/QALY for treatment-naïve and £7819/QALY for treatment-experienced. Benefit was driven by increased likelihood of achieving SVR, with consequent long-term utility gains. SMV + PR dominated TVR + PR and BOC + PR in both patient groups. This principally reflected the QALY benefit of an increased likelihood of SVR with SMV, combined with lower overall drug costs, due to reduced mean treatment duration.Conclusion:Compared to other currently licensed treatment options, SMV + PR represents a cost effective treatment option for patients with chronic genotype 1 HCV infection.

Cost-utility analysis of certolizumab pegol versus alternative tumour necrosis factor inhibitors available for the treatment of moderate-to-severe active rheumatoid arthritis in Spain.

BackgroundCertolizumab pegol, a PEGylated tumour necrosis factor (TNF)-inhibitor, improves the clinical signs and symptoms of rheumatoid arthritis (RA) when used in combination with methotrexate or as monotherapy. This study evaluatedthe cost-utility of certolizumab pegol versusTNF-inhibitors plus methotrexate in the treatment of moderate-to-severe RA in Spain.MethodsA Markov cohort health state transition model was developed to evaluate the cost-utility (costs and quality-adjusted life years [QALYs]) of certolizumab pegol versus other TNF-inhibitors licensed in Spain in 2009. Efficacy was measured using the American College of Rheumatology (ACR) responses at 6 months, based on adjusted indirect comparisons from published clinical trials. Utilities were derived from EQ-5D data from certolizumab pegol RA clinical trials. Clinical history and resource use data came from published literature. Unit costs were taken from Spanish databases or published data (cost year 2009). Base case analyses were conducted from the payer perspective, with a lifetime horizon, 3.5 % annual discounting rates for costs and outcomes, and 3 % inflation rate for 2009 onwards. One-way sensitivity analyses were conducted.ResultsThe average lifetime costs for certolizumab pegol, etanercept, adalimumab (every 2 weeks and weekly) and infliximab (3 mg/kg and 5 mg/kg) in combination with methotrexate were €140,971, €141,197, €139,148, €164,741, €136,961 and €152,561, respectively. The QALYs gained were 6.578, 6.462, 6.430 (for both adalimumab doses), 6.430, and 6.318 (for both infliximab doses), respectively. At a €30,000/QALY willingness-to-pay threshold, certolizumab pegol plus methotrexate dominated adalimumab weekly, etanercept, and infliximab 5 mg/kg, and was cost-effective versus adalimumab every 2 weeks and infliximab 3 mg/kg (all with methotrexate), with estimated ICERs of €12,346/QALY and €15,414/QALY, respectively. Certolizumab pegol monotherapy was more cost-effective versus adalimumab, and less expensive with similar health gains versus etanercept (6.416 QALYs vs 6.492). Univariate analysis showed ICERs to be sensitive to changes in time horizon, ACR response time point, baseline Heath Assessment Questionnaire (HAQ) score, and rate of HAQ-disability index deterioration after discontinuing treatment.ConclusionsThis analysis shows that certolizumab pegol is cost-effective compared with other TNF-inhibitors recommended in Spain for the treatment of RA.

Evaluation of disease burden and response to treatment in adults with type 1 gaucher disease using a validated disease severity scoring system (DS3)

BackgroundGD1-DS3 is an integrated assessment of type 1 Gaucher disease (GD1) burden based on bone, hematologic and visceral domains. We investigated this disease severity scoring system (DS3) methodology for initial assessment, long-term follow-up and evaluation of treatment responses.MethodsWe enrolled 133 treated adult GD1 patients. Baseline DS3 scores were calculated near the initial treatment date and patients stratified by severity as marked (DS3 6.00-19.00), moderate (DS3 3.00-5.99), mild (DS3 < 3.00). Follow-up scores were calculated annually. Minimal clinically important improvement (MCII), is defined as ΔDS3 of -3.1.ResultsPatient characteristics: N370S was the most common allele (118 patients had at least one), 52 were N370S/N370S (48/52 were Ashkenazi Jews), N370S/L444P was the most common genotype among non-Jews. Median age of treatment: 45 years; median follow-up: 14 years. Baseline DS3 scores: Patients with marked disease (N = 58; median 7.84) were least likely to be N370S homozygous (19 %) and most likely to have had splenectomy (53 %), early age at diagnosis (median 18 years) and major pre-treatment bone pathology (76 %). Among patients with moderate disease (N = 53; median 4.33), 49 % were N370S/N370S, 15.1 % had splenectomy and 17 % had major bone disease. Median age at diagnosis: 32 years. No patient with mild disease (N = 22; median 2.4) had splenectomy or major skeletal disease. Median age at diagnosis: 40 years. 68 % were N370S homozygous. Response to treatment: Health-state transitions occurred primarily during the early treatment years. At Year 5, among 48 evaluable patients with marked baseline disease, eight were unchanged in severity status whereas 40 had MCII of varying degrees with 11 scored as mild. Among 42 evaluable moderate patients, none worsened, 16 remained moderate and 26 improved to mild. Among 16 evaluable mild patients, 14 remained so and 2 had DS3 scores in the low moderate range.ConclusionsDS3 is effective for assessing disease burden in GD1 and for monitoring response. ERT was associated with MCII in DS3 scores in patients with high severity. Nevertheless, despite better DS3 scores with treatment, GD1 patients especially those with splenectomy and pre-treatment bone pathology, continued to have bone complications.

Cost-utility of denosumab for the treatment of postmenopausal osteoporosis in Spain.

BackgroundThe objective of this study was to estimate the cost-effectiveness of denosumab for fracture prevention compared with no treatment, generic bisphosphonates, and strontium ranelate in a cohort of osteoporotic postmenopausal women in Spain.MethodsA Markov model represented the possible health state transitions of Spanish postmenopausal women from initiation of fracture prevention treatment until age 100 years or death. The perspective was that of the Spanish National Health System. Fracture efficacy data for denosumab were taken from a randomized controlled trial. Fracture efficacy data for alendronate, ibandronate, risedronate, and strontium ranelate were taken from an independent meta-analysis. Data on the incidence of fractures in Spain were either taken from the published literature or derived from Swedish data after applying a correction factor based on the reported incidence from each country. Resource use in each health state was obtained from the literature, or where no data had been published, conservative assumptions were made. Utility values for the various fracture health states were taken from published sources. The primary endpoints of the model were life-years gained, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios for denosumab against the comparators.ResultsDenosumab reduced the risk of fractures compared with either no treatment or the other active interventions, and produced the greatest gains in life-years and QALYs. With an annual acquisition cost of €417.34 for denosumab, the incremental cost-effectiveness ratios for denosumab versus no treatment, alendronate, risedronate, and ibandronate were estimated at €6,823, €16,294, €4,895, and €2,205 per QALY gained, respectively. Denosumab dominated strontium ranelate. Sensitivity analyses confirmed the robustness of these findings.ConclusionOur analyses show that denosumab is a cost-effective intervention for fracture prevention in osteoporotic postmenopausal women in Spain compared with alendronate and risedronate, and is a dominant treatment option compared with strontium ranelate.

Cost effectiveness of endometrial ablation with the NovaSure(®) system versus other global ablation modalities and hysterectomy for treatment of abnormal uterine bleeding: US commercial and Medicaid payer perspectives.

ObjectivesAbnormal uterine bleeding (AUB) interferes with physical, emotional, and social well-being, impacting the quality of life of more than 10 million women in the USA. Hysterectomy, the most common surgical treatment of AUB, has significant morbidity, low mortality, long recovery, and high associated health care costs. Global endometrial ablation (GEA) provides a surgical alternative with reduced morbidity, cost, and recovery time. The NovaSure® system utilizes unique radiofrequency impedance-based GEA technology. This study evaluated cost effectiveness of AUB treatment with NovaSure ablation versus other GEA modalities and versus hysterectomy from the US commercial and Medicaid payer perspectives.MethodsA health state transition (semi-Markov) model was developed using epidemiologic, clinical, and economic data from commercial and Medicaid claims database analyses, supplemented by published literature. Three hypothetical cohorts of women receiving AUB interventions were simulated over 1-, 3-, and 5-year horizons to evaluate clinical and economic outcomes for NovaSure, other GEA modalities, and hysterectomy.ResultsModel analyses show lower costs for NovaSure-treated patients than for those treated with other GEA modalities or hysterectomy over all time frames under commercial payer and Medicaid perspectives. By Year 3, cost savings versus other GEA were $930 (commercial) and $3,000 (Medicaid); cost savings versus hysterectomy were $6,500 (commercial) and $8,900 (Medicaid). Coinciding with a 43%–71% reduction in need for re-ablation, there were 69%–88% fewer intervention/reintervention complications for NovaSure-treated patients versus other GEA modalities, and 82%–91% fewer versus hysterectomy. Furthermore, NovaSure-treated patients had fewer days of work absence and short-term disability. Cost-effectiveness metrics showed NovaSure treatment as economically dominant over other GEA modalities in all circumstances. With few exceptions, similar results were shown for NovaSure treatment versus hysterectomy.ConclusionModel results demonstrate strong financial favorability for NovaSure ablation versus other GEA modalities and hysterectomy from commercial and Medicaid payer perspectives. Results will interest clinicians, health care payers, and self-insured employers striving for cost-effective AUB treatments.

Evaluation of Disease Burden and Response to Treatment in Adults with Type 1 Gaucher Disase Using a Validated DS3 Severity Score Index

Evaluation of Disease Burden and Response to Treatment in Adults with Type 1 Gaucher Disase Using a Validated DS3 Severity Score Index

Characterizing longitudinal health state transitions among heroin, cocaine, and methamphetamine users

AimsCharacterize longitudinal patterns of drug use careers and identify determinants of drug use frequency across cohorts of primary heroin, methamphetamine (MA) and cocaine users. DesignPooled analysis of prospective cohort studies. SettingsIllicit drug users recruited from community, criminal justice and drug treatment settings in California, USA. ParticipantsWe used longitudinal data on from five observational cohort studies featuring primary users of heroin (N=629), cocaine (N=694) and methamphetamine (N=474). The mean duration of follow-up was 20.9 years. MeasurementsMonthly longitudinal data was arranged according to five health states (incarceration, drug treatment, abstinence, non-daily and daily use). We fitted proportional hazards (PH) frailty models to determine independent differences in successive episode durations. We then executed multi-state Markov (MSM) models to estimate probabilities of transitioning between health states, and the determinants of these transitions. FindingsAcross primary drug use types, PH frailty models demonstrated durations of daily use diminished in successive episodes over time. MSM models revealed primary stimulant users had more erratic longitudinal patterns of drug use, transitioning more rapidly between periods of treatment, abstinence, non-daily and daily use. MA users exhibited relatively longer durations of high-frequency use. Criminal engagement had a destabilizing effect on health state durations across drug types. Longer incarceration histories were associated with delayed transitions toward cessation. ConclusionsPH frailty and MSM modeling techniques provided complementary information on longitudinal patterns of drug abuse. This information can inform clinical practice and policy, and otherwise be used in health economic simulation models, designed to inform resource allocation decisions.

Modelling Cost Effectiveness in Neovascular Age-Related Macular Degeneration: The Impact of Using Contrast Sensitivity vs. Visual Acuity

BackgroundThe cost utility of treatments of age-related macular degeneration (AMD) is commonly assessed using health state transition models defined by levels of visual acuity. However, there is evidence that another measure of visual function, contrast sensitivity, may be better associated with utility than visual acuity. This paper investigates the difference in cost effectiveness resulting from models based on visual acuity and contrast sensitivity using the example of bevacizumab (Avastin) for neovascular AMD. The implications of the choice of outcome on structural uncertainty in the model are investigated.MethodHealth state transition Markov models based on levels of visual acuity and contrast sensitivity are used to represent the costs, health utilities and outcomes of the Avastin for choroidal neovascular age-related macular degeneration (ABC) trial. Health states are associated with costs and utilities based on literature values. Treatment outcomes from the ABC trial are used to predict transitions between states in both models. Total costs and quality-adjusted life-years (QALYs) are calculated for a cohort of patients treated over a defined number of model cycles.ResultsOver a 5-year time horizon, a contrast sensitivity model predicts a statistically significant (p < 0.05) 25 % greater QALY gain than the visual acuity model based on 10,000 Monte Carlo simulations. Bevacizumab is more effective and less costly than the comparator in the contrast sensitivity model and the visual acuity model.ConclusionThere is considerable structural uncertainty associated with the choice of outcome for modelling the cost effectiveness of AMD treatments. Bevacizumab has a higher incremental QALY gain and more favourable incremental cost-effectiveness ratio when cost effectiveness is assessed using contrast sensitivity outcomes compared with using visual acuity outcomes. Previous cost-effectiveness analyses may have underestimated the cost effectiveness of anti-vascular endothelial growth factor (anti-VEGF) therapy.

Cost-effectiveness of Telaprevir Combination Therapy for Chronic Hepatitis C

ObjectiveTo explore the expected long-term health and economic outcomes of telaprevir (TVR) plus peginterferon alfa-2a and ribavirin (PR), a regimen that demonstrated substantially increased sustained virologic response (SVR) compared with PR alone in adults with chronic genotype 1 hepatitis C virus (HCV) and compensated liver disease in the Phase III studies ADVANCE (treatment-naïve patients) and REALIZE (relapsers, partial responders, and null responders to previous PR treatment).Study DesignA decision-analytic model was developed to assess the cost-effectiveness of TVR+PR vs. PR in the United States (US).MethodsPatients first moved through the 72-week decision-tree treatment phase of the model and then entered the cyclic Markov post-treatment phase. Clinical data (patient characteristics, SVR rates, and adverse event rates and durations) were obtained from ADVANCE and REALIZE. Health-state transition probabilities, drug and other costs (in 2012/2013 US dollars), and utility values were obtained from the trials, published studies, and publicly available sources. Outcomes were discounted at 3% per year.ResultsRegardless of treatment history, patients receiving TVR+PR were projected to experience fewer liver-disease complications, more life-years, and more quality-adjusted life-years (QALYs) than patients receiving PR. In prior relapsers, TVR+PR was dominant, with lower total medical costs and more QALYs. For the other patient subgroups, incremental costs per QALY gained were between $16,778 (treatment-naïve patients) and $34,279 (prior null responders). Extensive sensitivity analyses confirmed robust model results.ConclusionsAt standard willingness-to-pay thresholds, TVR+PR represents a cost-effective treatment option compared with PR alone for patients with chronic genotype 1 HCV and compensated liver disease in the US. Future analyses are needed to compare TVR+PR with all existing HCV treatment options.