Epidemiology of Distal Renal Tubular Acidosis: A Study Using Linked UK Primary Care and Hospital Data.

INTRODUCTION: Distal renal tubular acidosis (dRTA), or RTA type 1, a rare inherited or acquired disease, is a disorder of the distal tubule caused by impaired urinary acid secretion. Due to associated conditions and nonspecific symptoms, dRTA may go undetected. This analysis aims to estimate the prevalence of dRTA in the UK Clinical Practice Research Datalink (CPRD) databases and extrapolate it to European Union Five (EU5) populations. METHODS: A retrospective analysis was conducted using the CPRD GOLD database and linked Hospital Episode Statistics (HES) data to identify diagnosed and potentially undiagnosed or miscoded patients (suspected patients). Patients' records with at least one diagnosis code for dRTA, RTA, specific autoimmune diseases, or renal disorders recorded between January 1987 and November 2017 were obtained and analyzed. An algorithm was developed to detect potentially undiagnosed/miscoded dRTA, based on associated conditions and prescriptions. RESULTS: A total of 216 patients with diagnosis of RTA or dRTA were identified (with 98 linked to hospital data), and 447 patients were identified as having suspected dRTA. dRTA prevalence for 2017 was estimated between 0.46 (recorded cases, of which 22.1% were considered primary) and 1.60 when including suspected cases (7.6% primary) per 10,000 people. Prescription and clinical records of diagnosed patients revealed a wide range of comorbidities and a need for pharmacological treatment to manage associated symptoms. CONCLUSION: The study provides new estimates of dRTA prevalence in Europe and suggests that patients may often be unreported or miscoded, potentially confounding appropriate disease management.

Estimating public health and economic benefits along 10 years of Fluzone® High Dose in the United States.

OBJECTIVE: The objective of this study was to estimate the public health and economic benefits (from a Medicare perspective) of Fluzone High-Dose® in the US elderly population, since its introduction in 2010. METHODS: A budget impact model was developed using a decision tree framework and applied over 9 influenza seasons (2010/11 to 2018/19). The decision tree model was designed to capture influenza cases, hospitalizations possibly related to influenza or laboratory confirmed influenza, and influenza-related deaths. The analysis included influenza vaccines recommended by ACIP since 2010: SD TIV (trivalent), SD QIV (quadrivalent), HD TIV, aTIV (adjuvanted), ccQIV (cell-cultured). Two strategies were compared to evaluate the impact of HD TIV: a 'with HD TIV' strategy representative of the US vaccine landscape, and a 'without HD TIV' where the absence of HD TIV was modelled. Clinical and economic inputs were based on public US data from the CDC and national databases, while data on vaccine effectiveness were extracted from published literature and clinical trials. The impact of HD TIV was further explored in five scenario analyses and deterministic sensitivity analyses (DSA). RESULTS: Over 10 years, it is estimated that HD TIV resulted in an averted 1,333,479 influenza cases, 769,476 medical visits, 40,004 ED presentations, 520,342 cardiorespiratory hospitalizations and 73,689 deaths and generated an absolute $4.6 billion in savings, translating into a return on investment of 214.4%. Hospitalizations costs represented 98.4% and 98.3% of the management costs in the 'with HD TIV' strategy and 'without HD TIV' strategy respectively. Hospitalizations and HD TIV relative vaccine efficacy vs SD TIV as a major cost driver were further confirmed in scenario analysis and DSA. HD TIV remained cost saving under all the scenarios. CONCLUSION: The model showed that HD TIV higher efficacy translated into increased averted health and economic outcomes. HD TIV represented a cost saving intervention from a payer perspective since its introduction.

Impact of childhood Dravet syndrome on care givers of patients with DS, a major impact on mothers.

BACKGROUND: The aim of this study was to understand the impact of Dravet syndrome (DS) on patients with Dravet syndrome and their families, with a focus on the social and economic impact on both mothers and fathers. METHODS: A French language on-line survey was distributed (October 2014-January 2015) for completion by caregivers of patients aged <18 years with DS. The survey was hosted on the French Dravet Syndrome Alliance website, and the survey link was provided to patients and caregivers during clinics at the Necker Hospital (Paris, France). RESULTS: Survey responses were available for 91 patients (median age 7.6 years; 81.6% SCN1A mutation positive). Total seizure frequency was >2 per week for 16.1% of patients, 1-8 per month for 55.2% and < 1 per month for 28.7%; tonic-clonic and myoclonic were the most frequent seizure types. Patients showed various degrees of intellectual disability and DS had a high impact on concentration and school learning in 70.1% and 80.5%. In addition, patients showed appetite disorders in 73.6%, sleep disorders in 72.4% and behavior disorders in 62.1%. Most parents were married (80.5%) with higher rates than the French general population (53.5%). Educational achievement and socio-professional categories for the parents were higher than observed in the French general population, while monthly net income was similar. Preparation of medication was generally done by the mother and father (46.0% of patients) or the mother only (37.9%). Most caregivers reported very low or no difficulty with treatment preparation and low or no risk of error. Parents typically spent <30 min per day on treatment preparation and administration and around 4 h per week for attending therapy appointments. Although most patients and parents were perceived to have good general health, mothers had a worse perception of their own general health than fathers. Compared with fathers, mothers reported a greater impact of caring for a child with DS on their social life, relationships with family and friends, time and energy, and professional life. CONCLUSION: Families caring for a child with DS experience considerable social and economic impact, with an apparent greater burden of care on the mother than the father.

Cost-effectiveness analysis of the nine-valent HPV vaccine in Italy.

BACKGROUND: In Italy HPV vaccination with the quadrivalent vaccine (Gardasil®) is offered actively and free of charge to girls aged 12 since 2007. A nine-valent vaccine (Gardasil 9®) received the European market authorization in 2015 to protect, with only 2 doses, against around 90% of all HPV positive cancers, over 80% of high-grade precancerous lesions and 90% of genital warts caused by HPV types 6/11. METHODS: A dynamic transmission model simulating the natural history of HPV-infections was calibrated to the Italian setting and used to estimate costs and QALYs associated with vaccination strategies. The analyses compared two strategies with the nine-valent vaccine (cervical cancer screening and vaccination in girls only or vaccination in boys and girls) to four alternative strategies (cervical cancer screening and vaccination with quadrialent vaccine in girls only, in both boys and girls, with bivalent vaccine in girls and screening strategy only). The National Health Service perspective was considered. CONCLUSION: The switch to the nine-valent vaccine in Italy can further reduce the burden associated to cervical cancer and HPV-related diseases and is highly cost-effective. RESULTS: Compared to the current vaccination program with quadrivalent vaccine, the nine-valent vaccine in a programme including girls and boys shows further reductions of 17% in the incidence of cervical cancer, 35 and 14% in anal cancer for males and females, as well as over a million cases of genital warts avoided after 100 years. The new technology is associated with an ICER of 10,463€ per QALY gained in universal vaccination, decreasing to 4483€ when considering the vaccine switch for girls-only.

An estimate of the public health impact and cost-effectiveness of universal vaccination with a 9-valent HPV vaccine in Germany.

INTRODUCTION: Since 2007, the German Standing Vaccination Committee recommends HPV vaccination for girls aged 12-17 with a 2- (Cervarix®) or 4-valent (Gardasil®) vaccine. A 9-valent vaccine (Gardasil 9®) recently received a European market authorization in 2015. METHODS: A dynamic transmission model was calibrated to the German setting and used to estimate costs and QALYs associated with vaccination strategies. RESULTS: Compared to the current vaccination program, the 9-valent vaccine extended to boys shows further reductions of 24% in the incidence of cervical cancer, 30% and 14% in anal cancer for males and females, as well as over a million cases of genital warts avoided after 100 years. The new strategy is associated with an ICER of 22,987€ per QALY gained, decreasing to 329€ when considering the vaccine switch for girls-only. CONCLUSION: Universal vaccination with the 9-valent vaccine can yield significant health benefits when compared to the current program.

Cost-effectiveness of everolimus plus reduced tacrolimus in de novo liver-recipients in the Italian setting.

INTRODUCTION: Long-term exposure to calcineurin inhibitor-based immunosuppressant (IS) therapy in liver transplant (LT) recipients is associated with renal complications. In the randomized trial H2304, everolimus + reduced-dose tacrolimus (EVR + rTAC) demonstrated equivalent efficacy and superior renal function compared to standard-dose tacrolimus. METHODS: To evaluate the cost-effectiveness of EVR + rTAC vs TAC, in de novo LT patients, a Markov model simulating both liver and kidney function was developed and estimated the long-term outcomes of IS following LT. The analysis used the Italian healthcare payer perspective. RESULTS: Patients treated with EVR + rTAC gained on average 1.92 years and 1.62 quality-adjusted life years (QALYs). The incremental cost-effectiveness ratios (ICER) were €35,851 and €42,567 for LY gained and QALY gained, respectively. For the hepatitis-c sub-population, the ICERs decreased to €22,519 and €30,658, respectively. CONCLUSION: EVR + rTAC improves survival and quality-of-life and is a cost-effective alternative to calcineurin-inhibitor monotherapy for patients requiring LT.

The use of Zostavax in Spain: the economic case for vaccination of individuals aged 50 years and older.

Background Population aging brings up a number of health issues, one of which is an increased incidence of herpes zoster (HZ) and its complication, post-herpetic neuralgia (PHN). Zostavax vaccine has recently become available to prevent HZ and PHN. This study evaluates the cost-effectiveness of vaccination against HZ in Spain considering a vaccination of the population aged 50 years and older and comparing this to the current situation where no vaccination is being administered. Methods An existing, validated, and published economic model was adapted to Spain using relevant local input parameters and costs from 2013. Results Vaccinating 30% of the Spanish population aged 50 years and older resulted in €16,577/QALY gained, €2025/HZ case avoided, and €5594/PHN case avoided under the third-party payer perspective. From a societal perspective, the ICERs increased by 6%, due to the higher price of the vaccine. The number needed to vaccinate to prevent one case was 20 for HZ, and 63 for PHN3. Sensitivity analyses showed that the model was most sensitive to the HZ and PHN epidemiological data, the health state utilities values, and vaccine price used. Conclusion Considering an acceptable range of cost-effectiveness of €30,000-€50,000 per QALY gained, vaccination of the 50+ population in Spain against HZ with a new vaccine, Zostavax, is cost-effective and makes good use of the valuable healthcare budget.

Systematic Literature Review and Meta-Analysis of Renal Function in Human Immunodeficiency Virus (HIV)-Infected Patients Treated with Atazanavir (ATV)-Based Regimens.

Some HIV antiretroviral therapies (ART) have been associated with renal toxicities, which become of increasing concern as HIV-infected patients age and develop comorbidities. The objective of this study was to evaluate the relative impact of atazanavir (ATV)-based regimens on the renal function of adult patients with HIV. We conducted a systematic literature review by searching PubMed, EMBASE, Cochrane library, and the CRD from 2000 until March 2013. Major HIV-related conferences occurring in the past two years were also searched. All randomized clinical trials and large cohort studies assessing renal function in treatment-naïve and/or treatment-experienced HIV patients on ATV-based regimens were included. Fixed-effect mixed-treatment network analyses were carried out on the most frequently reported renal outcomes. 23 studies met the inclusion criteria, and change in estimated glomerular filtration rate (eGFR) from baseline to 48 weeks was identified as the main outcome. Two networks including, respectively, six studies (using the Cockcroft-Gault method) and four studies (using MDRD and CKD-EPI) were analysed. With CG network, ATV/r + TDF/FTC was associated with lower impact on the decline of eGFR than ATV/cobicistat + TDF/FTC but with higher decrease in eGFR than ATV/r + ABC/3TC (difference in mean change from baseline in eGFR respectively +3.67 and -3.89). The use of ATV/cobicistat + TDF/FTC led to a similar decline in eGFR as EVG/cobicistat/TDF/FTC. With respect to third agents combined with TDF/FTC, ATV/r had a lower increase in eGFR in comparison to EFV, and no difference was shown when compared to SQV/r and DRV/r. The effect of ATV-based regimens on renal function at 48 weeks appears similar to other ART regimens and appears to be modest regardless of boosting agent or backbone, although TDF containing backbones consistently leads to greater decline in eGFR.

Cost-effectiveness analysis of a vaccination program for the prevention of herpes zoster and post-herpetic neuralgia in adults aged 50 and over in Germany.

Herpes zoster (HZ; shingles) is a common viral disease that affects the nerves and surrounding skin causing a painful dermatomal rash and leading to debilitating complications such as, mainly, post-herpetic neuralgia (PHN). Currently, there is no effective treatment for HZ and PHN. The objective of this study was to assess the cost-effectiveness of a HZ vaccination program in Germany. An existing Markov Model was adapted to the German healthcare setting to compare a vaccination policy to no vaccination on a lifetime time-horizon, considering 2 scenarios: vaccinating people starting at the age of 50 or at the age of 60 years, from the perspective of the statutory health insurance (SHI) and the societal perspective. According to the perspective, vaccinating 20% of the 60+ German population resulted in 162,713 to 186,732 HZ and 31,657 to 35,793 PHN cases avoided. Corresponding incremental cost-effectiveness ratios (ICER) were 39,306 €/QALY from the SHI perspective and 37,417 €/QALY from a societal perspective. Results for the 50+ German population ranged from 336,468 to 394,575 HZ and from 48,637 to 56,087 PHN cases avoided from the societal perspective. Corresponding ICER were 39,782 €/QALY from a SHI perspective and 32,848 €/QALY from a societal perspective. Sensitivity analyses showed that results are mainly impacted by discount rates, utility values and use of alternative epidemiological data.The model indicated that a HZ vaccination policy in Germany leads to significant public health benefits and could be a cost-effective intervention. The results were robust and consistent with local and international existing literature.

Cost utility of telaprevir-PR (peginterferon-ribavirin) versus boceprevir-PR and versus PR alone in chronic hepatitis C in The Netherlands.

BACKGROUND: The hepatitis C virus may lead to cirrhosis, liver cancer, liver transplant, and increased mortality. With standard treatment peginterferon-alpha and ribavirin (PR), sustained viral response (SVR) was less than 50 %. SVR rates improve greatly when PR is combined with telaprevir or boceprevir. OBJECTIVES: The aim of this study was to assess the cost utility of telaprevir-peginterferon-ribavirin (TPR) versus PR and boceprevir-peginterferon-ribavirin (BPR) in treatment-naïve (TN) and treatment-experienced (TE) adults with chronic hepatitis C in the Netherlands. METHODS: A Markov model with a lifelong time horizon and annual cycles was developed. Clinical data stemmed from phase III trials (TPR vs PR, BPR vs PR). A mixed treatment comparison (MTC) was developed to compare TPR and BPR indirectly. Unit costs and utilities based on EQ-5D were established in a Dutch cross-sectional study. Cost per quality-adjusted life-years (QALYs) was calculated according to the societal perspective. RESULTS: Treating TN patients with TPR generates 1.12 additional QALYs with €333 additional cost compared with PR, resulting in an incremental cost-utility ratio of €299/QALY. In TE patients, TPR dominates PR with cost savings (-€7,819) and 1.63 additional QALYs. TPR dominates BPR yielding additional QALYs (0.26 in TN; 0.71 in TE) and cost savings (-€7,296, -€18,144, respectively). CONCLUSIONS: TPR seems a cost-effective alternative to PR in TN patients and dominant in TE patients. TPR was a dominant, more effective and less costly alternative to BPR in both patient types. The cost effectiveness of both TPR and BPR is well below generally accepted willingness-to-pay thresholds and may be considered cost effective.

Cost-effectiveness of telaprevir in combination with pegylated interferon alpha and ribavirin in previously untreated chronic hepatitis C genotype 1 patients.

BACKGROUND: Telaprevir (T, TVR) is a direct-acting antiviral (DAA) used for the treatment of genotype 1 chronic hepatitis C virus (HCV) infection. The sustained virological response (SVR) rates, i.e., undetectable HCV RNA levels 24 weeks after the end of treatment, is what differentiate treatments. This analysis evaluated the cost-effectiveness of TVR combined with pegylated interferon (Peg-IFN) alfa-2a plus ribavirin (RBV), with Peg-IFN and RBV (PR) alone or with boceprevir (B, BOC) plus Peg-IFN alfa-2b and RBV, in naïve patients. METHODS: A Markov cohort model of chronic HCV disease progression reflected the pathway of naïve patients initiating anti-HCV therapy. SVR rates were derived from a mixed-treatment comparison including results from Phase II and III trials of TVR and BOC, and trials comparing both PR regimens. SVR has significant impact on survival, quality-of-life, and costs. Incremental cost per life year (LY) gained and quality-adjusted-life-year (QALY) gained were computed at lifetime, adopting the (National Health Service) NHS perspective. Cost and health outcomes were discounted at 3.5%. Uncertainty was assessed using deterministic and probabilistic sensitivity analyses. Sub-group analyses were also performed by interleukin (IL)-28B genotype and fibrosis stage. RESULTS: Higher costs and improved outcomes were associated with T/PR relative to PR alone, resulting in an ICER of £12,733 per QALY gained. T/PR retained a significant SVR advantage over PR alone and was cost-effective regardless of IL-28B genotype and fibrosis stages. T/PR regimen 'dominated' B/PR, generating 0.2 additional QALYs and reducing lifetime cost by £2758. Sensitivity analyses consistently resulted in ICERs less than £30,000/QALY for the T/PR regimen over PR alone. LIMITATIONS: No head-to-head trial provides direct evidence of better efficacy of T/PR vs B/PR. CONCLUSION: The introduction of TVR-based therapy for genotype 1 HCV patients is cost-effective for naïve patients at the £30,000 willingness-to-pay threshold, regardless of IL-28B genotype or fibrosis stage.

Cost-effectiveness of telaprevir in combination with pegylated interferon alpha and ribavirin in treatment-experienced chronic hepatitis C genotype 1 patients.

BACKGROUND: Telaprevir (TVR,T) and boceprevir (BOC,B) are direct-acting antivirals (DAAs) used for the treatment of chronic genotype 1 hepatitis C virus (HCV) infection. This analysis evaluated the cost-effectiveness of TVR combined with pegylated interferon (Peg-IFN) alfa-2a plus ribavirin (RBV) compared with Peg-IFN alfa-2a and RBV (PR) alone or BOC plus Peg-IFN alfa-2b and RBV in treatment-experienced patients. METHODS: A Markov cohort model of chronic genotype 1 HCV disease progression reflected the pathway of experienced patients retreated with DAA therapy. The population was stratified by previous response to treatment (i.e., previous relapsers, partial responders, and null responders). Sustained virologic response (SVR) rates were derived from a mixed-treatment comparison that included results from separate Phase III trials of TVR and BOC. Incremental cost per life year (LY) gained and quality-adjusted-life-year (QALY) gained were computed at lifetime, adopting the NHS perspective. Costs and health outcomes were discounted at 3.5%. Uncertainty was assessed using deterministic and probabilistic sensitivity analyses. Sub-group analyses were carried out by interleukin (IL)-28B genotype. RESULTS: Higher costs and improved outcomes were associated with T/PR relative to PR alone for all experienced patients (ICER of £6079). T/PR was cost-effective for each sub-group population with high SVR advantage in relapsers (ICER of £2658 vs £7593 and £20,875 for partial and null responders). T/PR remained cost-effective regardless of IL-28B sub-type. Compared to B/PR, T/PR prolonged QALYs by 0.57 and reduced lifetime costs by £13,960 for relapsers. For partial responders T/PR was less costly but less efficacious than B/PR, equating to an ICER of £128,117 per QALY gained. LIMITATIONS: No head-to-head trial provides direct evidence of better efficacy of T/PR vs B/PR. CONCLUSION: T/PR is cost-effective compared with PR alone in experienced patients regardless of treatment history and IL-28B genotype. Compared to B/PR, T/PR is always cost-saving but only more effective in relapsers.

Cost-effectiveness of Triple Therapy with Telaprevir for Chronic Hepatitis C Virus Patients in Germany.

Background: About 400,000-500,000 people are infected with hepatitis C in Germany. Long-term consequences are the development of liver cirrhosis and hepatocellular carcinoma. The introduction of first generation protease inhibitors has significantly improved the treatment of hepatitis C genotype 1 patients. The aim of the study was to assess the cost-effectiveness of triple therapy with telaprevir in Germany. Methods: We used a Markov model on disease progression and natural history to assess the cost-effectiveness of triple therapy with telaprevir compared to standard treatment with pegylated interferon and ribavirin. Model structure and inputs were discussed with clinical experts. Deterministic and probabilistic sensitivity analyses were performed to verify the robustness of results. Results: The base-case analyses shows that triple therapy results in higher costs (untreated patients: €48,446 vs. €30,691; previously treated patients: €63,228 vs. €48,603) and better outcomes (untreated patients: 16.85 qualily of life years [QALYs] vs. 15.97 QALYs; previously treated patients: 14.16 QALYs vs. 12.89 QALYs). The incremental cost-effectiveness ratio (ICER) was €20,131 per QALY and €30,567 per life year gained (LYG) for previously untreated patients. ICER in treatment experienced patients was €7,664 per QALY for relapse patients, €12,506 per QALY for partial responders and €28,429 per QALY for null responders. Results were robust in sensitivity analyses. Conclusion: Although triple therapy with telaprevir leads to additional costs, there is a high probability of being cost-effective for different thresholds. This health economic analysis makes an important contribution to current debates on cost savings and efficient resource allocation in the German healthcare sector.

Cost-effectiveness of highly purified omega-3 polyunsaturated fatty acid ethyl esters in the treatment of chronic heart failure: results of Markov modelling in a UK setting.

AIMS: A recent randomized placebo-controlled clinical trial has reported reductions in mortality and hospitalizations in patients with chronic heart failure (CHF) who were prescribed highly purified omega-3 polyunsaturated fatty acid ethyl esters (n-3 PUFA). This study aimed at evaluating the cost and benefits associated with their use in the treatment of CHF in a UK setting. METHODS AND RESULTS: Results from a recent clinical trial were used to develop a Markov model to project clinical outcomes while capturing relevant costs and patient quality of life. The model captured outcomes over a lifetime horizon from a UK National Health Service perspective, with direct costs accounted in 2009 GBP (£) and discounted at 3.5% together with clinical benefits. Results are presented in terms of life expectancy, quality-adjusted life expectancy, direct costs, and incremental cost-effectiveness ratios. In addition to standard therapy, n-3 PUFA vs. placebo increased lifetime direct costs by £993 (≈€1150), with additional quality-adjusted life expectancy of 0.079 quality-adjusted life years (QALYs), and mean lifetime costs of £12,636 (≈€14,600) per QALY gained. Probabilistic sensitivity analyses suggested a 60% likelihood of n-3 PUFA being regarded as cost-effective versus placebo at a willingness-to-pay threshold of £30,000 (≈€34,600) per QALY gained. CONCLUSIONS: By currently accepted standards of value for money in the UK; the addition of n-3 PUFA to optimal medical therapy for patients with heart failure is likely to be cost-effective.