Mapping MOS-HIV to HUI3 and EQ-5D-3L in Patients With HIV.

Objectives: The Medical Outcomes Study HIV Health Survey (MOS-HIV) is frequently used in HIV clinical trials; however, scores generated from the MOS-HIV are not suited for cost-effectiveness analyses as they do not assign utility values to health states. Our objective was to estimate and externally validate several mapping algorithms to predict Health Utilities Index Mark 3 (HUI3) and EQ-5D-3L utility values from the MOS-HIV. Methods: We developed and validated mapping algorithms using data from two HIV clinical trials. Data from the first trial (n = 367) formed the estimation data set for the HUI3 (4,610 observations) and EQ-5D-3L (4,662 observations) mapping algorithms; data from the second trial (n = 168) formed the HUI3 (1,135 observations) and EQ-5D-3L (1,152 observations) external validation data set. We compared ordinary least squares (OLS) models of increasing complexity with the more flexible two-part, beta regression, and finite mixture models. We assessed model performance using mean absolute error (MAE) and mean squared error (MSE). Results: The OLS model that used MOS-HIV dimension scores along with squared terms gave the best HUI3 predictions (mean observed 0.84; mean predicted 0.80; MAE 0.0961); the finite mixture model gave the best EQ-5D-3L predictions (mean observed 0.90; mean predicted 0.88; MAE 0.0567). All models produced higher prediction errors at the lower end of the HUI3 and EQ-5D-3L score ranges (<0.40). Conclusions: The proposed mapping algorithms can be used to predict HUI3 and EQ-5D-3L utility values from the MOS-HIV, although greater error may pose a problem in samples where a substantial proportion of patients are in poor health. These algorithms may be useful for estimating utility values from the MOS-HIV for cost-effectiveness studies when HUI3 or EQ-5D-3L data are not available.

Effect of management strategies and clinical status on costs of care for advanced HIV.

OBJECTIVES: To determine the association between preexisting characteristics and current health and the cost of different types of advanced human immunodeficiency virus (HIV) care. METHODS: Treatment-experienced patients failing highly active antiretroviral treatment (ART) in the United States, Canada, and the United Kingdom were factorial randomized to an antiretroviral-free period and ART intensification. Cost was estimated by multiplying patient-reported utilization by a unit cost. RESULTS: A total of 367 participants were followed for a mean of 15.3 quarters (range 1-26). Medication accounted for most (61.8%) of the $26,832 annual cost. Cost averaged $4147 per quarter for ART, $1981 for inpatient care, $580 for outpatient care, and $346 for other medications. Cost for inpatient stays, outpatient visits, and other medications was 171% higher (P <.01) and cost of ART was 32% lower (P <.01) when cluster of differentiation 4 (CD4) count was <50 cells/µL compared with periods when CD4 count was >200 cells/µL. Some baseline characteristics, including low CD4 count, high viral load, and HIV from injection drug use with hepatitis C coinfection, had a sustained effect on cost. CONCLUSIONS: The association between health status and cost depended on the type of care. Indicators of poor health were associated with higher inpatient and concomitant medication costs and lower cost for ART medication. Although ART has supplanted hospitalization as the most important cost in HIV care, some patients continue to incur high hospitalization costs in periods when they are using less ART. The cost of interventions to improve the use of ART might be offset by the reduction of other costs.

Cost-effectiveness of newer antiretroviral drugs in treatment-experienced patients with multidrug-resistant HIV disease.

OBJECTIVE: Newer antiretroviral drugs provide substantial benefits but are expensive. The cost-effectiveness of using antiretroviral drugs in combination for patients with multidrug-resistant HIV disease was determined. DESIGN: A cohort state-transition model was built representing treatment-experienced patients with low CD4 counts, high viral load levels, and multidrug-resistant virus. The effectiveness of newer drugs (those approved in 2005 or later) was estimated from published randomized trials. Other parameters were estimated from a randomized trial and from the literature. The model had a lifetime time horizon and used the perspective of an ideal insurer in the United States. The interventions were combination antiretroviral therapy, consisting of 2 newer drugs and 1 conventional drug, compared with 3 conventional drugs. Outcome measures were life-years, quality-adjusted life-years (QALYs), costs, and incremental cost-effectiveness. RESULTS: Substituting newer antiretroviral drugs increased expected survival by 3.9 years in advanced HIV disease. The incremental cost-effectiveness ratio of newer, compared with conventional, antiretroviral drugs was $75,556/QALY gained. Sensitivity analyses showed that substituting only one newer antiretroviral drug cost $54,559 to $68,732/QALY, depending on assumptions about efficacy. Substituting 3 newer drugs cost $105,956 to $117,477/QALY. Cost-effectiveness ratios were higher if conventional drugs were not discontinued. CONCLUSIONS: In treatment-experienced patients with advanced HIV disease, use of newer antiretroviral agents can be cost-effective, given a cost-effectiveness threshold in the range of $50,000 to $75,000 per QALY gained. Newer antiretroviral agents should be used in carefully selected patients for whom less expensive options are clearly inferior.

Effect of treatment interruption and intensification of antiretroviral therapy on health-related quality of life in patients with advanced HIV: a randomized, controlled trial.

BACKGROUND: The effect of antiretroviral therapy (ART) interruption or intensification on health-related quality of life (HRQoL) in advanced HIV patients is unknown. OBJECTIVE: To assess the impact of temporary treatment interruption and intensification of ART on HRQoL. DESIGN: A 2 x 2 factorial open label randomized controlled trial. SETTING: Hospitals in the United States, Canada, and the United Kingdom. PATIENTS: Multidrug resistant (MDR) HIV patients. INTERVENTION: Patients were randomized to receive a 12-wk interruption or not, and ART intensification or standard ART. MEASUREMENTS: The Health Utilities Index (HUI3), EQ-5D, standard gamble (SG), time tradeoff (TTO), visual analog scale (VAS), and the Medical Outcomes Study HIV Health Survey (MOS-HIV). RESULTS: There were no significant differences in HRQoL among the four groups during follow-up; however, there was a temporary significant decline in HRQoL on some measures within the interruption group during interruption (HUI3 -0.05, P = 0.03; VAS -5.9, P = 0.002; physical health summary -2.9, P = 0.001; mental health summary -1.9, P = 0.02). Scores declined slightly overall during follow-up. Multivariate analysis showed significantly lower HRQoL associated with some clinical events. Limitations. The results may not apply to HIV patients who have not experienced multiple treatment failures or who have not developed MDR HIV. CONCLUSIONS: Temporary ART interruption and ART intensification provided neither superior nor inferior HRQoL compared with no interruption and standard ART. Among surviving patients, HRQoL scores declined only slightly over years of follow-up in this advanced HIV cohort; however, approximately one-third of patients died during the trial follow up. Lower HRQoL was associated with adverse clinical events.

Determinants of the cost of health services used by veterans with HIV.

BACKGROUND: The effect of adherence, treatment failure, and comorbidities on the cost of HIV care is not well understood. OBJECTIVE: To characterize the cost of HIV care including combination antiretroviral treatment (ART). RESEARCH DESIGN: Observational study of administrative data. SUBJECTS: Total 1896 randomly selected HIV-infected patients and 288 trial participants with multidrug-resistant HIV seen at the US Veterans Health Administration (VHA). MEASURES: Comorbidities, cost, pharmacy, and laboratory data. RESULTS: Many HIV-infected patients (24.5%) of the random sample did not receive ART. Outpatient pharmacy accounted for 62.8% of the costs of patients highly adherent with ART, 32.2% of the cost of those with lower adherence, and 6.2% of the cost of those not receiving ART. Compared with patients not receiving ART, high adherence was associated with lower hospital cost, but no greater total cost. Individuals with a low CD4 count (<50 cells/mm) incurred 1.9 times the cost of patients with counts >500. Most patients had medical, psychiatric, or substance abuse comorbidities. These conditions were associated with greater cost. Trial participants were less likely to have psychiatric and substance abuse comorbidities than the random sample of VHA patients with HIV. CONCLUSIONS: Patients receiving combination ART had higher medication costs but lower acute hospital cost. Poor control of HIV was associated with higher cost. The cost of psychiatric, substance abuse, rehabilitation, and long-term care and medications other than ART, often overlooked in HIV studies, was substantial.

Dangerous omissions: the consequences of ignoring decision uncertainty.

Institutions with the responsibility for making adoption (reimbursement) decisions in health care often lack the remit to demand or commission further research: adoption decisions are their only policy instrument. The decision to adopt a technology also influences the prospects of acquiring further evidence because the incentives to conduct research are reduced and the ethical basis of further clinical trials maybe undermined. In these circumstances the decision maker must consider whether the benefits of immediate access to a technology exceeds the value of the evidence which maybe forgone for future patients. We outline how these expected opportunity losses can be established from the perspective of a societal decision maker with and without the remit to commission research, and demonstrate how these considerations change the appropriate decision rules in cost-effectiveness analysis. Importantly, we identify those circumstances in which the approval of a technology that is expected to be cost-effective should be withheld, i.e. when an 'only in research' recommendation should be made. We demonstrate that a sufficient condition for immediate adoption of a technology can provide incentives for manufacturers to reduce the price or provide additional supporting evidence. However, decisions based solely on expected net benefit provide no such incentives, may undermine the evidence base for future clinical practice and reduce expected net health benefits for the patient population.

A systematic review of continuous positive airway pressure for obstructive sleep apnoea-hypopnoea syndrome.

We conducted a systematic review of current evidence on the effectiveness of continuous positive airway pressure (CPAP) for treatment of obstructive sleep apnoea-hypopnoea syndrome (OSAHS). The primary outcomes were subjective sleepiness, using Epworth Sleepiness Scale (ESS) and objective sleepiness using Maintenance of Wakefulness Test (MWT) and Multiple Sleep Latency Test (MSLT). Mean difference (MD) in endpoints was used to compare CPAP to usual care, placebo and dental devices. The analysis was stratified by symptom and disease severity at baseline. CPAP significantly reduced ESS score compared to control (MD -2.7, 95% CI -3.45, -1.96). The benefit was greatest in patients whose symptoms were severe at baseline: severely symptomatic population (MD -5.0, -6.5, -3.5); moderate (MD -2.3, -3.0, -1.6); mild (MD -1.1, -1.8, -0.3). CPAP significantly improved MWT score compared to control (MD 3.3, 1.3, 5.3) but not on the MSLT. There was no statistically significant difference between CPAP and dental devices on the ESS, MWT or MSLT, in a population with moderate symptoms. There was some evidence of benefit for blood pressure with CPAP compared to control. CPAP is an effective treatment for OSAHS in moderate to severe symptomatic patients and there may be benefits for mild symptoms. Dental devices may be a treatment option for moderate symptoms.

Health-related quality of life in a randomized trial of antiretroviral therapy for advanced HIV disease.

OBJECTIVE: To assess and compare alternative approaches of measuring preference-based health-related quality of life (HRQoL) in treatment-experienced HIV patients and evaluate their association with health status and clinical variables. DESIGN: Cross-sectional study. SETTING: Twenty-eight Veterans Affairs hospitals in the United States, 13 hospitals in Canada, and 8 hospitals in the United Kingdom. PATIENTS: Three hundred sixty-eight treatment-experienced HIV-infected patients enrolled in the Options in Management with Antiretrovirals randomized trial. MEASUREMENTS: Baseline sociodemographic and clinical indicators and baseline HRQoL using the Medical Outcome Study HIV Health Survey (MOS-HIV), the EQ-5D, the EQ-5D visual analog scale (EQ-5D VAS), the Health Utilities Index Mark 3 (HUI3), and standard gamble (SG) and time trade-off (TTO) techniques. RESULTS: The mean (SD) baseline HRQoL scores were as follows: MOS-HIV physical health summary score 41.70 (11.16), MOS-HIV mental health summary score 44.76 (11.38), EQ-5D 0.77 (0.19), HUI3 0.59 (0.32), EQ-5D VAS 65.94 (21.71), SG 0.75 (0.29), and TTO 0.80 (0.31). Correlations between MOS-HIV summary scores and EQ-5D, EQ-5D VAS, and HUI3 ranged from 0.60 to 0.70; the correlation between EQ-5D and HUI3 was 0.73; and the correlation between SG and TTO was 0.43. Preference-based HRQoL scores were related to physical, mental, social, and overall health as measured by MOS-HIV. Concomitant medication use, CD4 cell count, and HIV viral load were related to some instruments' scores. CONCLUSIONS: On average, preference-based HRQoL for treatment-experienced HIV patients was decreased relative to national norms but also highly variable. Health status and clinical variables were related to HRQoL.

An economic analysis of continuous positive airway pressure for the treatment of obstructive sleep apnea-hypopnea syndrome.

OBJECTIVES: An important option for the medical treatment of obstructive sleep apnea-hypopnea syndrome (OSAHS) is continuous positive airway pressure (CPAP) during sleep. This study reports on the cost-effectiveness of CPAP compared with dental devices and lifestyle advice. The work was commissioned by the NHS HTA Programme to inform the National Institute of Health and Clinical Excellence's (NICE) appraisal of CPAP. METHODS: A Markov model compared the interventions over the expected patient lifetime. The primary measure of cost-effectiveness was the incremental cost per quality-adjusted life-year (QALY) gained. The QALY incorporated the impact of treatments on daytime sleepiness, blood pressure and health-related quality of life (HRQoL). RESULTS: On average, CPAP was associated with higher costs and QALYs compared with dental devices or lifestyle advice. In the base-case analysis, the incremental cost-effectiveness ratio (ICER) for CPAP compared with dental devices was around 4,000 pounds per QALY (2005--06 prices). The probability that CPAP is more cost-effective than dental devices or lifestyle advice at a threshold value of 20,000 pounds per QALY was 0.78 for men and 0.80 for women. Several sensitivity analyses were undertaken and it was found that the ICER for CPAP consistently fell below 20,000 pounds per QALY gained, apart from in a subgroup with mild disease. CONCLUSIONS: The model suggests that CPAP is cost-effective compared with dental devices and lifestyle advice for adults with moderate or severe symptomatic OSAHS at the cost-effectiveness thresholds used by NICE. This finding is reflected in the NICE guidance.

Methodological issues in undertaking independent cost-effectiveness analysis for NICE: the case of therapies for ADHD.

This paper outlines methodological challenges encountered in producing an independent economic evaluation for the National Institute for Health and Clinical Excellence (NICE) to inform its technology appraisal process. The analysis used to highlight these challenges is a recent evaluation of pharmacological treatments for attention deficit hyperactivity disorder (ADHD). The NICE reference case for economic evaluation is compared with the methods necessary to complete an evaluation given the evidence base for ADHD. The primary analysis deviated from NICE methods guidelines most noticeably in the time horizon. Identifying appropriate utility data was challenging, and the results were sensitive to the values used. Issues found in this evaluation are common to many technology appraisals. Although challenging to undertake, economic evaluation in disease areas such as ADHD has great potential to add value, making the limitations of the data explicit, combining available evidence in a systematic and transparent framework and identifying future research needs.