Methodological Challenges in the Economic Evaluation of a Gene Therapy for RPE65-Mediated Inherited Retinal Disease: The Value of Vision.

The emergence of gene therapies challenge health economists to evaluate interventions that are often provided to a small patient population with a specific gene mutation in a single dose with high upfront costs and uncertain long-term benefits. The objective of this study was to illustrate the methodological challenges of evaluating gene therapies and their implications by discussing four economic evaluations of voretigene neparvovec (VN) for the treatment of RPE65-mediated inherited retinal disease. The checklist for economic evaluations of gene therapies of Drummond et al. was applied to the economic evaluations of VN performed by US Institute for Clinical and Economic Review, two country adaptations of the company model in the UK and the Netherlands, and another US publication. The main differences in methodological choices and their impact on cost-effectiveness results were assessed and further explored with sensitivity analyses using the Dutch model. To enable comparison between the economic evaluations, costs were converted to US dollars. Different methodological choices were made in the economic evaluations of VN resulting in large differences in the incremental cost-effectiveness ratio varying from US$79,618 to US$643,813 per QALY. The chosen duration of treatment effect, source of utility values, discount rate and model structure had the largest impact on the cost-effectiveness. This study underlines the findings from Drummond et al. that standard methods can be used to evaluate gene therapies. However, given uncertainty about (particularly long-term) outcomes of gene therapies, guidance is required on the acceptable extrapolation of treatment effect of gene therapies and on how to handle the uncertainty around this extrapolation in scenario and sensitivity analyses to aid health technology assessment research and align submissions of future gene therapies.

Economic Evaluations of Pharmacogenetic and Pharmacogenomic Screening Tests: A Systematic Review. Second Update of the Literature.

OBJECTIVE: Due to extended application of pharmacogenetic and pharmacogenomic screening (PGx) tests it is important to assess whether they provide good value for money. This review provides an update of the literature. METHODS: A literature search was performed in PubMed and papers published between August 2010 and September 2014, investigating the cost-effectiveness of PGx screening tests, were included. Papers from 2000 until July 2010 were included via two previous systematic reviews. Studies' overall quality was assessed with the Quality of Health Economic Studies (QHES) instrument. RESULTS: We found 38 studies, which combined with the previous 42 studies resulted in a total of 80 included studies. An average QHES score of 76 was found. Since 2010, more studies were funded by pharmaceutical companies. Most recent studies performed cost-utility analysis, univariate and probabilistic sensitivity analyses, and discussed limitations of their economic evaluations. Most studies indicated favorable cost-effectiveness. Majority of evaluations did not provide information regarding the intrinsic value of the PGx test. There were considerable differences in the costs for PGx testing. Reporting of the direction and magnitude of bias on the cost-effectiveness estimates as well as motivation for the chosen economic model and perspective were frequently missing. CONCLUSIONS: Application of PGx tests was mostly found to be a cost-effective or cost-saving strategy. We found that only the minority of recent pharmacoeconomic evaluations assessed the intrinsic value of the PGx tests. There was an increase in the number of studies and in the reporting of quality associated characteristics. To improve future evaluations, scenario analysis including a broad range of PGx tests costs and equal costs of comparator drugs to assess the intrinsic value of the PGx tests, are recommended. In addition, robust clinical evidence regarding PGx tests' efficacy remains of utmost importance.

Cost effectiveness of lanthanum carbonate in chronic kidney disease patients in Spain before and during dialysis.

AIMS: In Spain, the first line treatment of hyperphosphatemia in Chronic Kidney Disease (CKD) consists of calcium-based phosphate binders (CB). However, their use is associated with vascular calcification and an increased mortality risk. The aim of this study was to assess the incremental cost-effectiveness of second-line Lanthanum Carbonate (LC) treatment in patients not responding to CB (calcium carbonate and calcium acetate). MATERIAL AND METHODS: A lifetime Markov model was developed considering three health states (predialysis, dialysis and death). Transitions between states and efficacy data were obtained from randomized clinical trials and the European Dialysis and Transplant Association Annual report. Mortality rate was adjusted with the relative risk related to serum phosphorus levels. According to the Spanish healthcare system perspective, only medical direct costs were considered. Dialysis costs (2013 prices in Euros) were obtained from diagnosis-related groups. Drug costs were derived from ex-factory prices, adjusted with 7.5% mandatory rebate. Quality of life estimates were based on a published systematic review. Costs and benefits were discounted at 3%. Deterministic and probabilistic sensitivity analyses (PSA) were conducted. RESULTS: At the end of simulation, costs per patient with LC therapy were 1,169 and 5,044 with CB alone. 4.653 Quality Adjusted Life Years (QALYs) were gained per patient treated with LC, and 4.579 QALYs with CB. CB therapy is dominated by the LC strategy (i.e. lower costs, higher QALYs). Assuming a 30,000/QALY threshold, LC was dominant in 100% of PSA simulations. CONCLUSIONS: LC is a cost-effective second line treatment of hyperphosphatemia in CKD patients irrespective of dialysis status in Spain.

Medication monitoring and optimization: a targeted pharmacist program for effective and cost-effective improvement of chronic therapy adherence.

UNLABELLED:   BACKGROUND: Community pharmacies provide a promising platform for monitoring and improving therapy adherence and providing pharmaceutical care. Structured methods and appropriate software are important tools to increase pharmacist effectiveness and improve health outcomes. In 2006, the Medication Monitoring and Optimization (MeMO) program was introduced in several community pharmacies in the Netherlands. MeMO facilitates targeted and continuous patient-centered pharmaceutical care around chronic medication, such as for osteoporosis, cardiovascular disease, and asthma/chronic obstructive pulmonary disease (COPD). OBJECTIVES: To describe the MeMO program and summarize findings from publications on its effectiveness, patient satisfaction, and cost-effectiveness.  METHODS: In the first part of this article, the MeMO program is extensively described. In the second part, a review of the evidence of effectiveness, cost-effectiveness, and patient satisfaction of the MeMO program is provided. Evidence is based on 5 previously published articles. RESULTS: The MeMO program starts with structured counseling sessions with patients at the initiation and follow-up of chronic therapies. This process is followed by a continuous phase in which patients' therapy adherence is monitored on a monthly basis, using standardized search algorithms in the pharmacy database. When the algorithm detects a patient's discontinuation of therapy, tailored interventions are used to improve adherence and optimize pharmacotherapy. For osteoporosis patients, treatment discontinuation with bisphosphonates after 1 year dropped from 31.7% to 16.1% (P less than 0.001). This program was shown to be cost-effective in patients initiating osteoporotic therapy. Future scenarios with lower drug prices (e.g., from generic prescribing) result in cost savings for the MeMO program. For lipid-lowering drugs, the MeMO program has been shown to lower therapy discontinuation after 1 year from 25.9% to 13.6% (P less than 0.001). By extrapolating these results to patients' lifetimes, the intervention was estimated to be cost-effective, with gains for primary prevention of cardiovascular events, and even cost saving in secondary prevention. Results from the ongoing MeMO asthma/COPD program are promising, showing marked improvements in therapy control and quality of life for asthma and COPD patients. Almost all patients participating in MeMO programs are satisfied with the pharmacy team and have gained knowledge of the effectiveness and administration of their medications and the importance of therapy adherence. CONCLUSION: The MeMO program is an effective and structured method to improve patients' adherence to chronic medication in the field of osteoporosis, lipid-lowering drugs, and asthma/COPD and is well received by patients. By targeting the program toward nonadherent and high-risk patients, the program showed favorable cost-effectiveness.

Improving adherence to lipid-lowering therapy in a community pharmacy intervention program: a cost-effectiveness analysis.

BACKGROUND: Pharmaceutical care in community pharmacies has been shown to improve adherence to chronic therapies. Long-term impact on clinical outcomes or medical cost savings, however, remains understudied.  OBJECTIVE: To estimate the cost-effectiveness of a pharmaceutical care intervention program in Dutch community pharmacies that improved patients' adherence to lipid-lowering therapy.  METHODS: An economic evaluation was performed using a time-dependent Markov model from the health care payer perspective. Participants were patients initiating lipid-lowering therapy for primary prevention (40%) or secondary prevention (60%) of cardiovascular events (CVEs). The intervention was the pharmaceutical care program MeMO (Medication Monitoring and Optimisation) in 9 community pharmacies in the Netherlands, based on continuous monitoring and optimization of lipid-lowering therapy in new patients. The follow-up period of the program was 1 year. The main outcome of the intervention program was discontinuation of lipid-lowering therapy. This outcome was extrapolated in the economic model to lifelong costs, quality of life, reductions in cardiovascular events, and incremental cost-effectiveness ratios. RESULTS: Patients in the MeMO program had a lower risk for therapy discontinuation, RR = 0.49 (0.37 to 0.66); the effectiveness was similar in primary and secondary prevention. In a cohort of 1,000 primary and secondary prevention patients, the MeMO program resulted in a reduction of 7 nonfatal strokes, 2 fatal strokes, 16 nonfatal myocardial infarctions (MIs), 7 fatal MIs, and 16 revascularizations over patients' lifetime. Additional medication, disease management, and intervention costs in the MeMO program were €411,000; the cost savings due to reduced CVEs were €443,000. The MeMO program resulted in 84 quality-adjusted life-years (QALYs) gained and net cost savings of €32,000. Clinical benefits and cost savings were highest in the secondary prevention population. CONCLUSION: Pharmaceutical care in community pharmacies can improve statin therapy adherence, resulting in better prevention of CVEs. The MeMO program resulted in considerable clinical benefits and net cost savings. Programs by community pharmacies targeted at improving adherence may provide good value for money, and health care insurers should consider reimbursing these activities.

A network meta-analysis of the relative efficacy of treatments for actinic keratosis of the face or scalp in Europe.

BACKGROUND: Several treatments are available for actinic keratosis (AK) on the face and scalp. Most treatment modalities were compared to placebo and therefore little is known on their relative efficacy. OBJECTIVES: To compare the different treatments for mild to moderate AK on the face and scalp available in clinical practice in Europe. METHODS: A network meta-analysis (NMA) was performed on the outcome "complete patient clearance". Ten treatment modalities were included: two 5-aminolaevulinic acid photodynamic therapies (ALA-PDT), applied as gel (BF-200 ALA) or patch; methyl-aminolevulinate photodynamic therapy (MAL-PDT); three modalities with imiquimod (IMI), applied as a 4-week or 16-week course with 5% imiquimod, or a 2-3 week course with 3.75% imiquimod; cryotherapy; diclofenac 3% in 2.5% hyaluronic acid; 0.5% 5-fluorouracil (5-FU); and ingenol mebutate (IMB). The only data available for 5% 5-FU was from one small study and was determined to be too limited to be reliably included in the analysis. For BF-200 ALA and MAL-PDT, data from illumination with narrow-band lights were selected as these are typically used in clinical practice. The NMA was performed with a random-effects Bayesian model. RESULTS: 25 trials on 5,562 patients were included in the NMA. All active treatments were significantly better than placebo. BF-200 ALA showed the highest efficacy compared to placebo to achieve total patient clearance. BF-200 ALA had the highest probability to be the best treatment and the highest SUCRA score (64.8% and 92.1%), followed by IMI 5% 4 weeks (10.1% and 74.2%) and 5-FU 0.5% (7.2% and 66.8%). CONCLUSIONS: This NMA showed that BF-200 ALA, using narrow-band lights, was the most efficacious treatment for mild to moderate AK on the face and scalp. This analysis is relevant for clinical decision making and health technology assessment, assisting the improved management of AK.

Improving inhaler adherence in patients with chronic obstructive pulmonary disease: a cost-effectiveness analysis.

BACKGROUND: The PHARMACOP-intervention significantly improved medication adherence and inhalation technique for patients with COPD compared with usual care. This study aimed to evaluate its cost-effectiveness. METHODS: An economic analysis was performed from the Belgian healthcare payer's perspective. A Markov model was constructed in which a representative group of patients with COPD (mean age of 70 years, 66% male, 43% current smokers and mean Forced Expiratory Volume in 1 second of % predicted of 50), was followed for either receiving the 3-month PHARMACOP-intervention or usual care. Three types of costs were calculated: intervention costs, medication costs and exacerbation costs. Outcome measures included the number of hospital-treated exacerbations, cost per prevented hospital-treated exacerbation and cost per Quality Adjusted Life-Year. Follow-up was 1 year in the basecase analysis. Sensitivity and scenario analyses (including long-term follow-up) were performed to assess uncertainty. RESULTS: In the basecase analysis, the average overall costs per patient for the PHARMACOP-intervention and usual care were €2,221 and €2,448, respectively within the 1-year time horizon. This reflects cost savings of €227 for the PHARMACOP-intervention. The PHARMACOP-intervention resulted in the prevention of 0.07 hospital-treated exacerbations per patient (0.177 for PHARMACOP versus 0.244 for usual care). Results showed robust cost-savings in various sensitivity analyses. CONCLUSIONS: Optimization of current pharmacotherapy (e.g. close monitoring of inhalation technique and medication adherence) has been shown to be cost-saving and should be considered before adding new therapies.

Clinical and economic impact of non-adherence in COPD: a systematic review.

BACKGROUND: Medication for Chronic Obstructive Pulmonary Disease (COPD) has shown to substantially reduce symptoms and slow progression of disease. However, non-adherence to medication is common and associated with worsened clinical and economic outcomes. OBJECTIVE: The objective of this study was to perform a systematic review of published literature to assess the impact of non-adherence to COPD medication on clinical and economic outcomes. METHODS: A search in PubMed and Web of Science databases was conducted of original studies published from database inception to 2012. Studies must report on the association between adherence to COPD medication and outcomes, published in English in peer-reviewed journals and full texts needed to be available. RESULTS: Twelve full articles were included in the review. Most studies were retrospective database studies. Seven studies reported on the association between adherence and clinical outcomes, two on mortality, three on costs, four on quality of life and one on work productivity. Results indicated a clear association between adherence and both clinical and economic outcomes. Evidence from studies revealed increased hospitalizations, mortality, quality of life and loss of productivity among non-adherent patients. CONCLUSION: This review revealed a clear association between non-adherence to COPD medication and worsened clinical and economic outcomes making non-adherent patients a priority for cost-effective interventions.

Cost-effectiveness of lanthanum carbonate in the treatment of hyperphosphatemia in dialysis patients: a Canadian payer perspective.

BACKGROUND: Hyperphosphatemia is a common and potentially harmful condition in patients with end-stage kidney disease. In Canada, first-line treatment of hyperphosphatemia consists primarily of calcium carbonate (CC). Lanthanum carbonate (LC) and sevelamer hydrochloride (SH) are non-calcium phosphate binders that have been used as second-line therapy in patients intolerant of or not responsive to CC. OBJECTIVES: The primary objective of the present study was to assess the costs and clinical benefits of second-line use of LC after therapy failure with CC in patients receiving dialysis, from a Canadian payer perspective. The secondary objective was to perform an economic comparison between second-line LC therapy and second-line SH therapy, from a Canadian payer perspective. Short-term outcomes were treatment response and cost per additional responder, and long-term outcomes were survival, number of all-cause hospitalizations, and quality of life. METHODS: A cost-effectiveness Markov model was populated with simulated cohorts of 1000 patients receiving incident dialysis, followed life-long. Patients not responsive to CC with a serum phosphate concentration >1.78 mmol/L (>5.5 mg/dL) received a trial regimen with LC. Patients not responsive to LC returned to CC therapy. Patient data from a randomized controlled trial of 800 patients receiving dialysis were used. Extensive (probabilistic) sensitivity analyses were performed. When available, model parameters were based on Canadian data or from a Canadian perspective. All costs are in 2010 Canadian dollars (C$). RESULTS: Results of the model estimated that in patients responsive to second-line LC therapy, survival increased, on average, 0.44 years (95% confidence interval [CI], 0.35-0.54) per patient when compared with continued CC therapy. The mean (range) costs per patient in the first year of treatment with LC was C$2600 (C$2400-C$2800). Over patients' lifetimes, the second-line LC strategy resulted in a gain of 48.8 (37.1-61.3) life-years and 29.3 (21.4-38.1) quality-adjusted life-years (QALYs). The cost-effectiveness of the second-line LC strategy was C$7900 (C$1800-C$14,600) per life-year and C$13,200 (C$3000-C$25,100) per QALY gained. Most sensitivity analyses did not change the cost-effectiveness outcomes; however, including unrelated future costs raised the incremental cost-effectiveness ratio to C$159,500 (95% confidence interval, C$133,300-C$191,600) per QALY gained. Compared with second-line SH therapy, second-line LC therapy had similar effectiveness and was 23% less expensive. CONCLUSIONS: Second-line treatment with LC is cost-effective in the treatment of end-stage kidney disease in patients with hyperphosphatemia, from a Canadian payer perspective. Second-line treatment with LC is less expensive, with similar effectiveness as second-line treatment with SH. The primary limitation of health economic evaluations of phosphate binders is the relative scarcity of clinical data on the association between phosphate concentration and long-term outcome.

Cost-effectiveness of lanthanum carbonate in the treatment of hyperphosphatemia in chronic kidney disease before and during dialysis.

OBJECTIVES: Hyperphosphatemia is a common and harmful condition in patients with chronic kidney disease (CKD). We determined the cost-effectiveness of the noncalcium-based phosphate binder lanthanum carbonate (LC) as second-line treatment of hyperphosphatemia after therapy failure with calcium-based binders (CB). METHODS: Two CKD populations were modeled: 1) predialysis CKD patients and 2) incident dialysis patients. Patients not responding to CB with a serum phosphate (SP) level >5.5 mg/dl received a trial with LC. Patients not responding to LC (SP >4.6 mg/dl) returned to CB treatment. Patient-level data were obtained from clinical trials in predialysis and dialysis. Time-dependent, life-long Markov models (discounting at 3.5% annually) were developed, using a UK National Health Service perspective. RESULTS: The health gains with second-line LC treatment compared to CB treatment were 44 and 56 quality-adjusted life-years (QALYs) for the predialysis and incident dialysis populations, respectively. Second-line LC was a cost-saving strategy in the predialysis population because of the cost-savings of delayed CKD progression. Second-line LC was cost-effective at £6900 (90% probability interval: £5800-£8300) per QALY gained in the dialysis population. Results were robust to plausible variations in other model parameters; inclusion of future unrelated dialysis costs had a large influence on cost-effectiveness estimates. CONCLUSIONS: Second-line treatment with LC is associated with considerable clinical benefits and good value for money in CKD, irrespective of dialysis status. These results support Kidney Disease Outcomes Quality Initiative guidelines to treat CKD patients with hyperphosphatemia irrespective of dialysis status.

Using a genetic, observational study as a strategy to estimate the potential cost-effectiveness of pharmacological CCR5 blockade in dialysis patients.

BACKGROUND AND OBJECTIVE: Randomized clinical trials are expensive and time consuming. Therefore, strategies are needed to prioritise tracks for drug development. Genetic association studies may provide such a strategy by considering the differences between genotypes as a proxy for a natural, lifelong, randomized at conception, clinical trial. Previously an association with better survival was found in dialysis patients with systemic inflammation carrying a deletion variant of the CC-chemokine receptor 5 (CCR5). We hypothesized that in an analogous manner, pharmacological CCR5 blockade could protect against inflammation-driven mortality and estimated if such a treatment would be cost-effective. METHODS: A genetic screen and treat strategy was modelled using a decision-analytic Markov model, in which patients were screened for the CCR5 deletion 32 polymorphism and those with the wild type and systemic inflammation were treated with pharmacological CCR5 blockers. Kidney transplantation and mortality rates were calculated using patient level data. Extensive sensitivity analyses were performed. RESULTS: The cost-effectiveness of the genetic screen and treat strategy was &OV0556;18 557 per life year gained and &OV0556;21 896 per quality-adjusted life years gained. Concordance between the genetic association and pharmacological effectiveness was a main driver of cost-effectiveness. Sensitivity analyses showed that even a modest effectiveness of pharmacological CCR5 blockade would result in a treatment strategy that is good value for money. CONCLUSION: Pharmacological blockade of the CCR5 receptor in inflamed dialysis patients can be incorporated in a potentially cost-effective screen and treat programme. These findings provide formal rationale for clinical studies. This study illustrates the potential of genetic association studies for drug development, as a source of Mendelian randomized evidence from an observational setting.

Review of regulatory recommendations for orphan drug submissions in the Netherlands and Scotland: focus on the underlying pharmacoeconomic evaluations.

BACKGROUND: Pharmacoeconomic evaluations of new drug therapies are often required for reimbursement or guidance decisions. However, for orphan drugs, country-specific requirements exist. In the Netherlands, orphan drug developers can be exempted from providing a full pharmacoeconomic evaluation, whereas in Scotland, no such exceptions can be made, although additional modifying factors specific to orphan products may be considered. OBJECTIVE: The aim of the present work was to identify differences in the outcomes of the recommendations for orphan drugs for rare diseases between 2 European countries: Scotland and the Netherlands. METHODS: All orphan drug reports to the Dutch Committee for Pharmaceutical Assistance (Commissie Farma-ceutische Hulp [CFH]) and orphan drugs guidance issued by the Scottish Medicines Consortium (SMC) through May 2009 were reviewed from the respective organizations' Web sites. The following were gathered from the pharmacoeconomic analyses and recommendations for reimbursement in the Netherlands or guidance for drug use in Scotland: drug indication, outcome of pharmacoeconomic evaluation, recommendation, and exact date. RESULTS: Dossiers for 38 orphan drugs were submitted to the CFH; 37 were submitted to the SMC. Only 1 submission to the CFH included a full pharmacoeconomic analysis; all other reports included only a cost analysis. Twenty-four submissions to the SMC were accompanied by a full pharmacoeconomic evaluation; no information could be obtained for 4 drugs. The remaining reports either did not include a cost-effectiveness analysis or were deemed insufficient by the SMC. Forty-three percent (10/23) of the cost-utility analyses submitted to the SMC reported an unfavorable outcome of more than £30,000/ quality-adjusted life-year (QALY) gained; of these, only 2 (20%) reporting incremental cost-utility ratios of £43.717 to £81.000 were granted a restricted positive recommendation. The CFH gave positive recommendations for reimbursement for 36 of 38 submissions (95%). Of the 37 orphan drugs submitted to the SMC, 19 (51%) received a positive recommendation for use. Seventy-three percent (8/11) of submissions to the SMC with an unfavorable cost-effectiveness estimate (ie, more than £30,000 [€34,000 or US $48,000] per QALY gained) received a negative recommendation for reimbursement. CONCLUSIONS: Ninety-five percent of orphan drug submissions were approved for reimbursement in the Netherlands, compared with 51% in Scotland, during the period of interest. Moreover, cost-effectiveness or cost-utility analyses were included in 24 of 37 submissions in Scotland, compared with only 1 of 38 in the Netherlands.

Cost-effectiveness of ACE inhibitor therapy to prevent dialysis in nondiabetic nephropathy: influence of the ACE insertion/deletion polymorphism.

INTRODUCTION: End-stage renal disease is associated with high health-care costs and low quality of life compared with chronic kidney disease. The renoprotective effectiveness of angiotensin-converting enzyme inhibitors (ACEi) is largely determined by the ACE insertion/deletion (I/D) polymorphism. We determined the cost-effectiveness of ACEi therapy in nondiabetic nephropathy for the ACE II/ID and for the ACE DD genotype separately. Furthermore, we considered a selective screen-and-treat strategy in which patients are prescribed alternative, more effective, therapy based on their ACE (I/D) polymorphism. METHODS: Time-dependent Markov models were constructed; cohorts of 1000 patients were followed for 10 years. Data were mainly gathered from the Ramipril Efficacy In Nephropathy trial. Both univariate and probabilistic sensitivity analyses were performed. RESULTS: ACEi therapy dominated placebo in both the ACE II/ID group (euro15 826, and 0.091 quality-adjusted life years gained per patient) and the ACE DD group (euro105 104 and 0.553 quality-adjusted life years gained). Sensitivity analyses showed 30.2% probability of ACEi being not cost-effective in the ACE II/ID group, against an almost 100% probability of cost-effectiveness in the ACE DD group. A selective screen-and-treat strategy should incorporate an alternative therapy for patients with the ACE II/ID genotype with an at least 9.1% increase in survival time compared with ACEi therapy to be cost-effective. Sensitivity analyses show that higher effectiveness and lower costs of the alternative therapy improve the cost-effectiveness of a screening strategy. CONCLUSION: ACEi therapy is a cost-saving treatment compared with placebo in nondiabetic nephropathy, irrespective of ACE (I/D) genotype. However, ACEi therapy saved more costs and more health gains were achieved in the ACE DD genotype than in the ACE II/ID genotype. An alternative treatment featuring a modest increase in effectiveness compared with ACEi therapy for patients with the ACE II/ID genotype can be incorporated in a cost-effective or even cost-saving screen-and-treat strategy.

Cost-effectiveness of varicella vaccination programs: an update of the literature.

Varicella is one of the most common infectious diseases in childhood, caused by the varicella zoster virus. Although vaccines are available, there are only a few countries with an early-childhood vaccination program. Most countries mainly focus on vaccination of high-risk groups, such as susceptible healthcare workers. One of the main concerns with a routine early-childhood vaccination program is a potential (temporal) increase of the incidence of herpes zoster among elderly adults. In this review, we focus on the cost-effectiveness of varicella vaccination and on the methodology used in the health-economic studies. In particular, we focus on the perspective adopted, type of model used, the modeled effect on herpes zoster, the vaccine efficacy and price, and on the value of time lost by infection. The vast majority of studies show vaccination of high-risk groups - including susceptible adolescents - to be cost saving. Routine early-childhood vaccination programs are always cost saving if indirect costs of production losses are included, or cost effective, as long as the potential negative effects on zoster are not taken into account. We note that most studies included in the review used old vaccine prices and a single dose of the varicella vaccine, whereas multiple doses are now becoming the standard. Despite that, those aspects limit the timeliness of our review and we believe that the current work does provide useful insights in the cost-effectiveness of varicella vaccination.

Pharmacoeconomic evaluations of pharmacogenetic and genomic screening programmes: a systematic review on content and adherence to guidelines.

The fields of pharmacogenetics and pharmacogenomics have become important practical tools to progress goals in medical and pharmaceutical research and development. As more screening tests are being developed, with some already used in clinical practice, consideration of cost-effectiveness implications is important. A systematic review was performed on the content of and adherence to pharmacoeconomic guidelines of recent pharmacoeconomic analyses performed in the field of pharmacogenetics and pharmacogenomics. Economic analyses of screening strategies for genetic variations, which were evidence-based and assumed to be associated with drug efficacy or safety, were included in the review. The 20 papers included cover a variety of healthcare issues, including screening tests on several cytochrome P450 (CYP) enzyme genes, thiopurine S-methyltransferase (TMPT) and angiotensin-converting enzyme (ACE) insertion deletion (ACE I/D) polymorphisms. Most economic analyses reported that genetic screening was cost effective and often even clearly dominated existing non-screening strategies. However, we found a lack of standardization regarding aspects such as the perspective of the analysis, factors included in the sensitivity analysis and the applied discount rates. In particular, an important limitation of several studies related to the failure to provide a sufficient evidence-based rationale for an association between genotype and phenotype. Future economic analyses should be conducted utilizing correct methods, with adherence to guidelines and including extensive sensitivity analyses. Most importantly, genetic screening strategies should be based on good evidence-based rationales. For these goals, we provide a list of recommendations for good pharmacoeconomic practice deemed useful in the fields of pharmacogenetics and pharmacogenomics, regardless of country and origin of the economic analysis.