Specialty drug coverage varies between health plans' medical and pharmacy benefit policies.

BACKGROUND: In an effort to control drug spending, health plans are increasingly shifting specialty drugs from their medical benefit to the pharmacy benefit. One consequence of this trend is that some health plans have both a medical and a pharmacy coverage policy for the same drug. OBJECTIVE: To examine how frequently health plans issue medical and pharmacy benefit policies for the same specialty drug and to evaluate the concordance between plans' medical and pharmacy policies when plans issue both policy types. METHODS: We identified specialty drug coverage policies from the Tufts Medical Center Specialty Drug Evidence and Coverage Database, which includes policies issued by 17 of the largest US commercial health plans. Policies were current as of August 2020. We determined plans that issued both medical and pharmacy policies. Next, we identified drugs with "medical-pharmacy policy pairs," ie, drugs for which a plan issued both a medical and a pharmacy policy. For these pairs, we compared the plan's policies while accounting for the following coverage criteria: patient subgroups (patients must meet certain clinical criteria), prescriber requirements (a specialist must prescribe the drug), and step therapy protocols (patients must first fail alternative treatments). We considered medical-pharmacy policy pairs to be discordant if coverage criteria differed, eg, the medical policy included a prescriber requirement but the pharmacy policy did not. RESULTS: Eight plans issued separate medical and pharmacy benefit coverage policies for the same specialty drug and indication. Among these 8 plans, we identified 1,619 medical-pharmacy policy pairs. Eighty-six percent of pairs were concordant (1,386/1,619), and 14% were discordant (233/1,619). Discordance was most often due to differences in plans' application of step therapy protocols (184/233), followed by prescriber requirements (52/233) and patient subgroups (25/233). Forty pairs were discordant in multiple ways. Of discordant pairs, medical policies were more restrictive 41% (96/233) of the time; pharmacy policies were more restrictive 54% (125/233) of the time; 5% of the time (12/233), the medical policy was more restrictive in some ways, but the pharmacy policy was more restrictive in others. Overall, plans imposed coverage restrictions in their medical and pharmacy policies with similar frequencies. CONCLUSIONS: Commercial health plans' medical and pharmacy coverage policies for the same specialty drugs tended to be concordant, although we found coverage criteria to be discordant 14% of the time. Medical and pharmacy policies that are inconsistent in their coverage criteria and restrictions complicate, and potentially hinder, patients' access to specialty drugs. DISCLOSURES: Drs Kauf, O'Sullivan, and Strand were employees of Alkermes, Inc., when the study was conducted and may own stock in the company. Mx Levine, Mr Panzer, and Dr Chambers have no conflicts of interest to disclose. This research study was supported by Alkermes, Inc.

Inhibitor clinical burden of disease: a comparative analysis of the CHESS data.

BACKGROUND: Patients with hemophilia and inhibitors generally face greater disease burden compared to patients without inhibitors. While raising awareness of relative burden may improve the standard of care for patients with inhibitors, comparative data are sparse. Analyzing data drawn from the Cost of Haemophilia across Europe - a Socioeconomic Survey (CHESS) study, the aim of this study was to compare the clinical burden of disease in patients with severe hemophilia with and without inhibitors. Hemophilia specialists (N = 139) across five European countries completed an online survey between January-April 2015, providing demographic, clinical and 12-month ambulatory/secondary care activity data for 1285 patients. Patients with hemophilia who currently presented with inhibitors and those who never had inhibitors were matched on baseline characteristics via propensity score matching. Outcomes were compared between the two cohorts using a paired t-test or Wilcoxon signed-rank or McNemar's test. RESULTS: The proportion of patients who currently presented with inhibitors was 4.5% (58/1285). Compared to PS-matched patients without inhibitors, patients with inhibitors experienced more than twice the mean annual number of bleeds (mean ± standard deviation, 8.29 ± 9.18 vs 3.72 ± 3.95; p < .0001) and joint bleeds (2.17 ± 1.90 vs 0.98 ± 1.15; p < .0001), and required more hemophilia-related (mean ± standard deviation, 1.79 ± 1.83 vs 0.64 ± 1.13) and bleed-related hospitalizations (1.86 ± 1.88 vs 0.81 ± 1.26), hemophilia-related consultations (9.30 ± 4.99 vs 6.77 ± 4.47), and outpatient visits (22.09 ± 17.77 vs 11.48 ± 16.00) (all, p < .001). More than one-half (53.5%) experienced moderate/severe pain necessitating medication compared to one-third (32.8%) of patients without inhibitors (p = .01). CONCLUSIONS: Patients with hemophilia and inhibitors exhibited greater clinical burden and higher resource utilization compared to their peers without inhibitors. Strategies for improving the standard of care may alleviate burden in this population.

Cost-effectiveness of ceftolozane/tazobactam compared with piperacillin/tazobactam as empiric therapy based on the in-vitro surveillance of bacterial isolates in the United States for the treatment of complicated urinary tract infections.

BACKGROUND: A challenge in the empiric treatment of complicated urinary tract infection (cUTI) is identifying the initial appropriate antibiotic therapy (IAAT), which is associated with reduced length of stay and mortality compared with initial inappropriate antibiotic therapy (IIAT). We evaluated the cost-effectiveness of ceftolozane/tazobactam compared with piperacillin/tazobactam (one of the standard of care antibiotics), for the treatment of hospitalized patients with cUTI. METHODS: A decision-analytic Monte Carlo simulation model was developed to compare the costs and effectiveness of empiric treatment with either ceftolozane/tazobactam or piperacillin/tazobactam in hospitalized adult patients with cUTI infected with Gram-negative pathogens in the US. The model applies the baseline prevalence of resistance as reported by national in-vitro surveillance data. RESULTS: In a cohort of 1000 patients, treatment with ceftolozane/tazobactam resulted in higher total costs compared with piperacillin/tazobactam ($36,413 /patient vs. $36,028/patient, respectively), greater quality-adjusted life years (QALYs) (9.19/patient vs. 9.13/patient, respectively) and an incremental cost-effectiveness ratio (ICER) of $6128/QALY. Ceftolozane/tazobactam remained cost-effective at a willingness to pay of $100,000 per QALY compared to piperacillin/tazobactam over a range of input parameter values during one-way and probabilistic sensitivity analysis. CONCLUSIONS: Model results show that ceftolozane/tazobactam is likely to be cost-effective compared with piperacillin/tazobactam for the empiric treatment of hospitalized cUTI patients in the United States.

Systematic review and network meta-analysis of tedizolid for the treatment of acute bacterial skin and skin structure infections caused by MRSA.

BACKGROUND: Tedizolid, the active moiety of tedizolid phosphate, is approved in the United States, the European Union, Canada and a number of other countries for the treatment of acute bacterial skin and skin structure infections (ABSSSI) caused by certain susceptible bacteria, including methicillin-resistant Staphylococcus aureus (MRSA). This network meta-analysis (NMA) evaluates the comparative effectiveness of tedizolid and other antibacterials indicated for the treatment of ABSSSI caused by MRSA. METHODS: Systematic review of 10 databases was undertaken to inform an NMA to estimate the relative effectiveness of tedizolid and established monotherapy comparators (ceftaroline, daptomycin, linezolid, teicoplanin, tigecycline, vancomycin) for treating MRSA-associated ABSSSI. Randomized controlled trials enrolling adults with ABSSSI or complicated skin and skin structure infections caused by suspected/documented MRSA were eligible for inclusion. Networks were developed based on similarity of study design, patient characteristics, outcome measures and available data. Outcomes of interest included clinical response at end of therapy (EOT), post-therapy evaluation (PTE) or test-of-cure assessment and treatment discontinuations resulting from adverse events (AEs). Bayesian NMA was conducted for each outcome using fixed-effects and random effects models. RESULTS: Literature searches identified 3,618 records; 15 trials met the inclusion criteria and were considered suitable for NMA comparison. In fixed-effects models, tedizolid had higher odds of clinical response at EOT (odds ratio [OR], 1.7; credible interval, 1.0, 3.0) and PTE than vancomycin (OR, 1.6; credible interval, 1.1, 2.5). No differences in odds of clinical response at EOT or PTE were observed between tedizolid and other comparators. There was no evidence of a difference among treatments for discontinuation due to AEs. Results from random effects and fixed-effects models were generally consistent. CONCLUSIONS: Tedizolid was superior to vancomycin for clinical response at EOT and PTE. There was no evidence of a difference between tedizolid and other comparators and no evidence of a difference between tedizolid and all comparators when evaluating discontinuation due to AEs. These findings suggest that tedizolid provides an alternative option for the management of serious skin infections caused by suspected or documented MRSA. This study is subject to the limitations inherent in all NMAs, and the results should be interpreted accordingly.

An open-label, pragmatic, randomized controlled clinical trial to evaluate the comparative effectiveness of daptomycin versus vancomycin for the treatment of complicated skin and skin structure infection.

BACKGROUND: Treatment of complicated skin and skin structure infection (cSSSI) places a tremendous burden on the health care system. Understanding relative resource utilization associated with different antimicrobials is important for decision making by patients, health care providers, and payers. METHODS: The authors conducted an open-label, pragmatic, randomized (1:1) clinical study (N = 250) to compare the effectiveness of daptomycin with that of vancomycin for treatment of patients hospitalized with cSSSI caused by suspected or documented methicillin-resistant Staphylococcus aureus infection. The primary study end point was infection-related length of stay (IRLOS). Secondary end points included health care resource utilization, cost, clinical response, and patient-reported outcomes. Patient assessments were performed daily until the end of antibiotic therapy or until hospital discharge, and at 14 days and 30 days after discharge. RESULTS: No difference was found for IRLOS, total LOS, and total inpatient cost between cohorts. Hospital LOS contributed 85.9% to the total hospitalization cost, compared with 6.4% for drug costs. Daptomycin showed a nonsignificant trend toward a higher clinical success rate, compared with vancomycin, at treatment days 2 and 3. In the multivariate analyses, vancomycin was associated with a lower likelihood of day 2 clinical success (odds ratio [OR] = 0.498, 95% confidence interval [CI], 0.249-0.997; P < 0.05). CONCLUSION: This study did not provide conclusive evidence of the superiority of one treatment over the other in terms of clinical, economic, or patient outcomes. The data suggest that physician and patient preference, rather than drug acquisition cost, should be the primary driver of initial antibiotic selection for hospitalized patients with cSSSI. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01419184 (Date: August 16, 2011).

Economic Impact of Alvimopan Considering Varying Definitions of Postoperative Ileus.

BACKGROUND: Prolonged postoperative ileus (POI) is the predominant cause of extended hospitalization after bowel resection surgery. Alvimopan accelerates gastrointestinal recovery, potentially reducing health care costs. We examined the value of alvimopan in reducing prolonged POI and length of stay for patients undergoing abdominal surgery using different definitions of POI. STUDY DESIGN: We developed a decision analytic model to examine costs and outcomes associated with postoperative treatment with either an accelerated care pathway (ACP) only or alvimopan+ACP. To represent an overall perspective for alvimopan, data from four phase 3 bowel resection trials and one phase 4 radical cystectomy trial were used to populate the model with 3 different definitions of POI. The period analyzed included start of surgery to 7 days post discharge. Costs were obtained from standard US costing sources and are reported in 2015 US dollars. Due to variations in published definitions of POI, alternative definitions based on adverse event reports, NG tube insertion, and time to food toleration were examined. RESULTS: The combined clinical trial data included 1,003 ACP and 1,013 alvimopan+ACP patients. When POI was reported as an adverse event, the incidence of POI was significantly lower with alvimopan+ACP (n = 70 [7%]) vs ACP alone (n = 148 [15%]; p < 0.0001). Time to discharge order written was shorter for patients with POI who were treated with alvimopan+ACP than with ACP (202 ± 115 hours vs 266 ± 138 hours; p < 0.0001). As a result, costs were $731 lower with alvimopan+ACP ($17,835) vs ACP ($18,566). Alternative definitions of POI produced similar results. CONCLUSIONS: The addition of alvimopan to existing treatment pathways for patients undergoing abdominal surgery can reduce overall hospital costs.

Psoriasis patients' willingness to accept side-effect risks for improved treatment efficacy.

BACKGROUND: Previous studies suggest that efficacy is more important than side-effect risks to psoriasis patients. However, those studies did not consider potentially fatal risks of biologic treatments. OBJECTIVE: To quantify the risks patients are willing to accept for improvements in psoriasis symptoms. METHODS: Adults with a self-reported physician diagnosis of psoriasis were recruited through the National Psoriasis Foundation. Using a discrete-choice experiment, patients completed a series of nine choice questions, each including a pair of hypothetical treatments. Treatments were defined by severity of plaques, body surface area (BSA), and 10-year risks of tuberculosis, serious infection and lymphoma. RESULTS: For complete clearance of 25% BSA with mild plaques, respondents (n = 1608) were willing to accept a 20% (95% confidence interval: 9-26%) risk of serious infection, 10% (5-15%) risk of tuberculosis and 2% (1-3%) risk of lymphoma. For complete clearance of 25% BSA with severe plaques, respondents were willing to accept a 54% (48-62%) risk of serious infection, 36% (28-49%) risk of tuberculosis and 8% (7-9%) risk of lymphoma. LIMITATIONS: Respondents were asked to evaluate hypothetical scenarios. Actual treatment choices may differ. CONCLUSION: Respondents were willing to accept risks above likely clinical exposures for improvements in psoriasis symptoms. Individual risk tolerances may vary.

Alvimopan, a peripherally acting µ-opioid receptor antagonist, is associated with reduced costs after radical cystectomy: economic analysis of a phase 4 randomized, controlled trial.

PURPOSE: We evaluated the effect of alvimopan treatment vs placebo on health care utilization and costs related to gastrointestinal recovery in patients treated with radical cystectomy in a randomized, phase 4 clinical trial. MATERIALS AND METHODS: Resource utilization data were prospectively collected and evaluated by cost consequence analysis. Hospital costs were estimated from 2012 Medicare reimbursement rates and medication wholesale acquisition costs. Differences in base case mean costs between the study cohorts for total postoperative ileus related costs (hospital days, study drug, nasogastric tubes, postoperative ileus related concomitant medication and postoperative ileus related readmissions) and total combined costs (postoperative ileus related, laboratory, electrocardiograms, nonpostoperative ileus related concomitant medication and nonpostoperative ileus related readmission) were evaluated by probabilistic sensitivity analysis using a bootstrap approach. RESULTS: Mean hospital stay was 2.63 days shorter for alvimopan than placebo (mean±SD 8.44±3.05 vs 11.07±8.23 days, p=0.005). Use of medications or interventions likely intended to diagnose or manage postoperative ileus was lower for alvimopan than for placebo, eg total parenteral nutrition 10% vs 25% (p=0.001). Postoperative ileus related health care costs were $2,340 lower for alvimopan and mean total combined costs were decreased by $2,640 per patient for alvimopan vs placebo. Analysis using a 10,000-iteration bootstrap approach showed that the mean difference in postoperative ileus related costs (p=0.04) but not total combined costs (p=0.068) was significantly lower for alvimopan than for placebo. CONCLUSIONS: In patients treated with radical cystectomy alvimopan decreased hospitalization cost by reducing the health care services associated with postoperative ileus and decreasing the hospital stay.

Influence of explanatory and confounding variables on HRQoL after controlling for measurement bias and response shift in measurement.

The purpose of this study was to examine the influence of explanatory and confounding variables on health-related quality of life after accounting for response shift, measurement bias and response shift in measurement using structural equation modeling. Hypertensive patients with coronary artery disease randomized to anti-hypertensive treatment, completed the ShortForm-36 questionnaire at both baseline and 1 year (n = 788). Three measurement biases were found and all three were considered as response shift in measurement. Older patients reported worse scores for both physical functioning (PF) and role-physical at baseline and 1 year later compared to younger patients; and males reported better PF than females after conditioning on the latent trait of general physical health. Before controlling for response shift, patients' PF scores were not statistically different over time; however, PF scores significantly improved (p < 0.01) after controlling for recalibration response shift. Assessment of how patients perceive their change in health-related quality of life over time is warranted.

Assessment of response shift using two structural equation modeling techniques.

OBJECTIVE: To identify response shift using two structural equation modeling (SEM) techniques. STUDY DESIGN AND SETTING: Hypertensive patients (n = 909) with coronary artery disease (CAD) completed SF-36 surveys at both baseline and 1-year follow-up. Response shift was identified using Oort and Schmitt SEM techniques. The type of response shift linked to changes in various parameters of the SEM measurement model is defined differently for both SEM approaches. Effect sizes were calculated for the impact of response shift on the change of SF-36 domain scores when using the Oort approach. RESULTS: Both Oort and Schmitt SEM approaches identified response shift only in the SF-36 physical functioning (PF) scale. The effect size of recalibration on the change of PF domain scores when using the Oort approach was -0.12. CONCLUSION: This study showed that hypertensive patients with CAD experienced a response shift over a 1-year period. Both the SEM approaches identified response shift (uniform recalibration using the Oort approach and recalibration using the Schmitt approach); however, both approaches use different parameters to define and test response shift. We found that either the variation in analytic methods or the sample used may influence the identification and type of response shift.

Patients' willingness to accept the risks and benefits of new treatments for chronic hepatitis C virus infection.

BACKGROUND: Some patients with chronic hepatitis C virus (HCV) infection forego treatment due to concerns about treatment efficacy, treatment duration, and side effects. OBJECTIVE: The purpose of this study was to quantify patient preferences among possible outcomes associated with new, direct-acting antiviral agents (DAAs) for the treatment of HCV infection and determine which treatment features are most important to patients in making treatment decisions. METHODS: Adult participants with a self-reported physician diagnosis of HCV infection in five countries completed a web-enabled, choice-format conjoint analysis survey. The survey presented participants with 20 treatment-choice questions. Each treatment-choice question included a pair of hypothetical treatment profiles with varying levels of six attributes: treatment duration; chance of getting rid of the virus completely (i.e. likelihood of a sustained virologic response [SVR]); weeks on an additional, third medicine (i.e. a DAA); risk of a severe rash; risk of severe anemia; and number of times a day the third medicine is taken. Treatment-choice questions were based on a pre-determined experimental design with known statistical properties. Random-parameters logit was used to estimate preference weights for all attribute levels and the mean relative importance of each attribute. RESULTS: 284 participants completed the survey. Likelihood of an SVR was the most important outcome to participants, followed by severe anemia risk, severe rash risk, therapy type (a combination of total weeks of treatment and weeks on the third medicine), and dosing of the third medicine. Controlling for other factors, preferences were similar across all therapy types examined. CONCLUSION: Patients with HCV infection indicate a willingness to accept an increased risk of side effects for sufficient improvement in the likelihood of treatment response.

Spillover adherence effects of fixed-dose combination HIV therapy.

The impact of fixed-dose combination (FDC) products on adherence to other, non-fixed regimen components has not been examined. We compared adherence to a third antiretroviral (ART) component among patients receiving a nucleoside reverse transcriptase inhibitor (NRTI) backbone consisting of the FDC Epzicom(®), GlaxoSmithKline Inc, Research Triangle Park, NC (abacavir sulfate 600 mg + lamivudine 300 mg; FDC group) versus NRTI combinations taken as two separate pills (NRTI Combo group) using data from a national sample of 30 health plans covering approximately 38 million lives from 1997 to 2005. Adherence was measured as the medication possession ratio (MPR). Multivariate logistic regression compared treatment groups based on the likelihood of achieving ≥95% adherence, with sensitivity analyses using alternative thresholds. MPR was assessed as a continuous variable using multivariate linear regression. Covariates included age, gender, insurance payer type, year of study drug initiation, presence of mental health and substance abuse disorders, and third agent class. The study sample consisted of 650 FDC and 1947 NRTI Combo patients. Unadjusted mean adherence to the third agent was higher in the FDC group than the NRTI Combo group (0.92 vs 0.85; P < 0.0001). In regression analyses, FDC patients were 48% and 39% more likely to achieve 95% and 90% third agent adherence, respectively (P ≤ 0.03). None of the other MPR specifications achieved comparable results. Among managed care patients, use of an FDC appears to substantially improve adherence to a third regimen component and thus the likelihood of achieving the accepted standard for adherence to HIV therapy of 95%.

Trends in the prevalence of thrombocytopenia among individuals infected with hepatitis C virus in the United States, 1999-2008.

BACKGROUND: Thrombocytopenia is associated with the natural history of hepatitis C virus (HCV) infection and anti-viral therapy. Recent, national estimates of the clinical burden of thrombocytopenia among HCV-infected individuals in the United States are unavailable. Bi-yearly data from the 1999-2000 to 2007-2008 National Health and Nutrition Examination Surveys (NHANES) were used to examine the prevalence of thrombocytopenia among HCV-infected individuals in the United States. RESULTS: Among 467 HCV-infected individuals in the survey (weighted population = 3,597,039), mean weighted age was 46.7 years (standard deviation = 15.5) and 61.7% were male. Overall, 7.6% met the study definition of TCP at the 150 × 10(9)/L threshold; 4.5%, 2.0%, and 0.8% had platelet counts below 125, 100, and 75 × 10(9)/L, respectively. The 2-year weighted prevalences of thrombocytopenia (150 × 10(9)/L threshold) from 1999-2008 were 4.9%, 8.6%, 6.5%, 4.1%, and 12.9%. The unadjusted biannual time trend (odds ratio) was 1.16 (95% confidence interval = 0.82-1.64). In the two adjusted models, the odds by time ranged from 1.24-1.40, depending on whether the model included demographic or laboratory variables or both, but did not reach statistical significance. Age was positively and significantly related to thrombocytopenia status. CONCLUSIONS: As the HCV-infected population ages, the prevalence of thrombocytopenia is expected to rise. This study provides limited evidence of such an effect at the national level.

Cost-effectiveness of respiratory syncytial virus prophylaxis in various indications.

OBJECTIVES: To evaluate the cost-effectiveness of immunoprophylaxis against respiratory syncytial virus (RSV) infections with palivizumab based on actual cost and observed incidence rates in various pediatric risk groups. DESIGN: Decision tree analysis comparing children with various combinations of the following indications: chronic lung disease, congenital heart disease, or prematurity (≤32 weeks gestation), and children with none of these indications. One-way sensitivity analyses and Monte Carlo simulations were used to quantify parameter uncertainty. SETTING: Florida during the 2004-2005 RSV season. PARTICIPANTS: A total of 159,790 Medicaid-eligible children aged 0 to 2 years. INTERVENTION: Palivizumab prophylaxis compared with no prophylaxis. OUTCOMES MEASURE: Incremental cost (2010 US dollars) per hospitalization for RSV infection avoided. RESULTS: The mean cost of palivizumab per dose ranged from $1661 for infants younger than 6 months of age to $2584 for children in their second year of life. Among preterm infants younger than 6 months of age without other indications, immunoprophylaxis with palivizumab cost $302,103 (95% confidence interval, $141,850-$914,798) to prevent 1 RSV-related hospitalization. Given a mean cost of $8910 for 1 RSV-related hospitalization in this subgroup, palivizumab would be cost-neutral at a per-dose cost of $47. Incremental cost-effectiveness ratios for the other subgroups ranged from $361,727 to more than $1.3 million per RSV-related hospitalization avoided in children up to 2 years of age with chronic lung disease and no additional risk factors. Younger age and multiple indications were associated with improvements in the incremental cost-effectiveness ratio. CONCLUSIONS: The cost of immunoprophylaxis with palivizumab far exceeded the economic benefit of preventing hospitalizations, even in infants at highest risk for RSV infection.

Economic efficiency of genetic screening to inform the use of abacavir sulfate in the treatment of HIV.

BACKGROUND: Abacavir sulfate (abacavir) is associated with a hypersensitivity reaction (HSR) that affects 5-8% of patients. While serious complications are rare, failure to identify it, or abacavir re-challenge following HSR, can be fatal. Genetic screening for HLA-B*5701 can identify patients who are likely to experience an HSR and reduces the incidence of the reaction. OBJECTIVE: We assessed the intrinsic and practical value, from the US healthcare system perspective, of prospective HLA-B*5701 screening among a population of antiretroviral-naive patients without elevated risk factors for cardiovascular disease, plasma HIV RNA >100,000 copies/mL, or pre-existing renal insufficiency. METHODS: Two approaches were used to evaluate the costs and benefits of prospective screening. First, the efficiency of HLA-B*5701 screening compared with no screening prior to abacavir initiation (intrinsic value of screening) was evaluated using a 60-day decision-tree model. Next, the practical value of screening was assessed using a lifetime discrete-event simulation model that compared HLA-B*5701 screening prior to abacavir use versus initiation with a tenofovir-containing regimen. Screening-effectiveness parameters were taken from an open-label trial that incorporated screening prior to abacavir initiation and other published studies. Treatment efficacy was derived from clinical trials. Modelling assumptions, costs ($US, year 2007 values) and other parameters were derived from published sources, primary data analysis and expert opinion. Multiple one-way sensitivity and scenario analyses were performed to assess parameter uncertainty. The primary outcome measure for the short-term screening versus no screening analysis was cost per patient. For the long-term analysis, outcomes were presented as QALYs. Costs and effects were discounted at 3% per year. RESULTS: Over the first 60 days of treatment, prospective screening prior to abacavir initiation cost an additional $US17 per patient and avoided 537 HSRs per 10,000 patients. The per-patient cost of screening was sensitive to the cost of the genetic test, HSR costs and screening performance. In the lifetime model, screening-informed abacavir use was more effective and less costly than initiation with a tenofovir-containing regimen in the base case and in sensitivity analyses. CONCLUSIONS: Our results suggest that prospective HLA-B*5701 screening prior to abacavir initiation produces cost savings and should become a standard component of HIV care.

Methodological concerns with economic evaluations of meningococcal vaccines.

The evolution of meningococcal vaccines illustrates nicely the incremental technological process that is common to much medical innovation and particularly appropriate to economic analysis. However, the economic evaluation of vaccines is complicated by several features unique to vaccines, including the possibility of indirect (herd immunity) benefits and the shear breadth of vaccination strategies available to decision makers. As with the vaccines themselves, the modelling approaches applied to the economic evaluation of meningococcal vaccines have evolved to become increasingly complex. Despite such innovation, concerns remain about the quality of economic studies of meningococcal vaccines. This article reviews evaluations of meningococcal vaccine strategies in developed countries and provides recommendations for future work in this area. Four potentially problematic areas in the existing literature are identified - indirect costs, herd immunity, quality of life and comparison programmes - and approaches to these issues are discussed. Recommendations for reporting a 'minimum analysis profile' case are also made. Although comparisons across studies are difficult at best, recent work shows that incorporating the indirect benefits and costs of vaccination substantially improves cost effectiveness.