Affordability and cost-effectiveness: decision-making on the cost-effectiveness plane.

Much recent research interest has focused on handling uncertainty in cost-effectiveness analysis and in particular the calculation of confidence intervals for incremental cost-effectiveness ratios (ICERs). Problems of interpretation when ICERs are negative have led to two important and related developments: the use of the net-benefit statistic and the presentation of uncertainty in cost-effectiveness analysis using acceptability curves. However, neither of these developments directly addresses the problem that decision-makers are constrained by a fixed-budget and may not be able to fund new, more expensive interventions, even if they have been shown to represent good value for money. In response to this limitation, the authors introduce the 'affordability curve' which reflects the probability that a programme is affordable for a wide range of threshold budgets. The authors argue that the joint probability an intervention is affordable and cost-effective is more useful for decision-making since it captures both dimensions of the decision problem faced by those responsible for health service budgets.

New aspects in health economic studies of prevention and treatment of osteoporosis.

This review updates the current knowledge with regard to important new clinical data in the field of osteoporosis interventions and discusses the implications for future health economics studies in this field.

Applying some UK Prospective Diabetes Study results to Switzerland: the cost-effectiveness of intensive glycaemic control with metformin versus conventional control in overweight patients with type-2 diabetes.

OBJECTIVE: The results of the metformin substudy of the United Kingdom Prospective Diabetes Study (UKPDS) were applied through modelling techniques to the Swiss setting, allowing a cost-effectiveness analysis of the management of overweight type-2 diabetes patients with either conventional glycaemic control or intensive control with metformin from the Swiss third-party payer perspective. METHODS: Occurrence of diabetes-related complications was simulated using a Markov model. Probabilities for complications were taken from the UKPDS, and costs were retrieved from published sources. Total direct costs (costs of diabetes therapy plus costs of treating complications) and survival over an 11-year period were determined for cohorts randomised to either conventional glycaemic control or intensive control with metformin. Changes in life expectancy were calculated for conventional versus intensive control with metformin. Extensive sensitivity analysis was performed. RESULTS: Mean costs per patient over the 11-year follow-up period (discounted at 5% per annum) were CHF 10,877 and CHF 9950 for patients randomised to either conventional control or intensive control with metformin respectively. Intensive control with metformin led to improved survival (0.43 life-years gained per patient) over the 11-year-period. Outcomes were most sensitive to variations in the acquisition costs of metformin. Changes in the event rates and costs related to myocardial infarction, renal failure, and stroke also had important impacts. CONCLUSIONS: Within the limitations of the modelling study, intensive glycaemic control with metformin was cost- and life-saving in overweight type-2 diabetes patients in the Swiss setting.

The cost-effectiveness of different management strategies for type I diabetes: a Swiss perspective.

AIMS/HYPOTHESIS: A computer model was developed to determine the health outcomes and economic consequences of different combinations of diabetes interventions in newly diagnosed patients with Type I (insulin-dependent) diabetes in Switzerland. METHODS: We modelled seven complications of diabetes: hypoglycaemia, ketoacidosis, acute myocardial infarction, stroke, lower extremity amputation, nephropathy, and retinopathy. Transition probabilities and costs were taken from published literature. The Swiss health insurance payer perspective was taken. Various combinations of diabetes management strategies, including intensive or conventional insulin therapy and screening and treatment strategies for renal and eye disease were defined. Life expectancy, cumulative incidences of complications, and mean expected total lifetime costs per patient were calculated under six different management strategies. Incremental cost-effectiveness ratios were calculated in terms of costs per life-year gained compared with conventional insulin therapy alone. RESULTS: The addition of screening for microalbuminuria and retinopathy followed by appropriate treatment, if detected, were cost saving, with reduction in cumulative incidence of end stage renal disease and blindness respectively, and, in the case of microalbulminuria screening and treatment, an improvement in life expectancy. Intensive therapy improved life expectancy but increased total lifetime costs. CONCLUSION/INTERPRETATION: Optimal management of Type I diabetic patients, including secondary and tertiary prevention, leads to reduced complications and improved life expectancy, with the increased costs of prevention offset to varying degrees by cost savings due to complications avoided.

Cost-effectiveness of azithromycin for preventing Mycobacterium avium complex infection in HIV-positive patients in the era of highly active antiretroviral therapy. The Swiss HIV Cohort Study.

We conducted a cost-effectiveness analysis to determine the clinical and economic consequences of Mycobacterium avium complex (MAC) prophylaxis in HIV-infected patients in the era of highly active antiretroviral therapy (HAART) in a health care system with access unrestricted by financial barriers. The analysis was performed from a health care perspective and compared azithromycin (1200 mg/week) with no prophylaxis over a period of 10 years based on data from the Swiss HIV Cohort Study (SHCS) and randomized controlled trials. The main outcome measures were: expected survival; average health care costs; and cost-effectiveness in 1997 Swiss francs ( pound1 corresponds to about 2.3 CHF) per life-year saved. In patients with an initial CD4 count <50 cells/mm(3) and no AIDS, azithromycin increased expected survival by 4 months. In patients with AIDS, HAART durability had a major impact on expected survival and costs. Incremental survival increased from 2 to 4 months if we assumed a 10 year, instead of a 3 year, HAART effect. The cost-effectiveness of azithromycin relative to no prophylaxis in patients without AIDS was between 47,000 CHF (3-year HAART effect) and 60,000 CHF (10-year HAART effect) per life-year saved. The cost-effectiveness ratio increased to 118,000 CHF per life-year saved in patients with symptomatic AIDS. In conclusion, in the era of HAART, MAC prophylaxis with azithromycin increases expected survival and reduces health care costs substantially. Starting MAC prophylaxis in patients without AIDS is more effective and cost-effective than in patients with AIDS.

Sensitivity analysis on a chance node with more than two branches.

Sensitivity analysis is an essential part of decision analysis. The literature on medical decision analysis suggests the use of two-branch chance nodes in decision trees to avoid logical inconsistencies during sensitivity analysis. The authors show that the two-branch decomposition is not appropriate for sensitivity analysis when multiple outcomes from a single state cannot be disentangled into a sensible sequence of events. They recommend retaining the natural structure of the tree and propose two sensitivity-analysis methods for use on chance nodes with three or more branches.

Systematic validation of disease models for pharmacoeconomic evaluations. Swiss HIV Cohort Study.

Pharmacoeconomic evaluations are often based on computer models which simulate the course of disease with and without medical interventions. The purpose of this study is to propose and illustrate a rigorous approach for validating such disease models. For illustrative purposes, we applied this approach to a computer-based model we developed to mimic the history of HIV-infected subjects at the greatest risk for Mycobacterium avium complex (MAC) infection in Switzerland. The drugs included as a prophylactic intervention against MAC infection were azithromycin and clarithromycin. We used a homogenous Markov chain to describe the progression of an HIV-infected patient through six MAC-free states, one MAC state, and death. Probability estimates were extracted from the Swiss HIV Cohort Study database (1993-95) and randomized controlled trials. The model was validated testing for (1) technical validity (2) predictive validity (3) face validity and (4) modelling process validity. Sensitivity analysis and independent model implementation in DATA (PPS) and self-written Fortran 90 code (BAC) assured technical validity. Agreement between modelled and observed MAC incidence confirmed predictive validity. Modelled MAC prophylaxis at different starting conditions affirmed face validity. Published articles by other authors supported modelling process validity. The proposed validation procedure is a useful approach to improve the validity of the model.

Cost effectiveness of highly active antiretroviral therapy in HIV-infected patients. Swiss HIV Cohort Study.

BACKGROUND: Highly active antiretroviral therapy (HAART) has become the most important strategy for treating HIV infection in developed countries; however, access to HAART might vary under different funding policies. The Swiss health care system provides unrestricted access to HAART for all patients who need these newer combination therapies. This study investigated the impact of this funding policy on the society and health care system. METHODS: A cost-effectiveness analysis with natural history data and productivity estimates was based on the Swiss HIV Cohort Study. A random sample of patient charts was used to estimate health care costs. In addition to a base-case scenario, a pessimistic and an optimistic scenario of natural disease history was developed. Costs were expressed in 1997 Swiss francs (100 CHF correspond to about US$67) and effects as projected years of life gained. RESULTS: In the analysis limited to health care costs, on the basis of projected survival in each scenario, the cost-effectiveness ratio was 33,000 CHF (base case), 14,000 CHF (optimistic), and 45,000 CHF (pessimistic) per year of life gained. When changes in productivity were included, cost savings occurred in the base-case and optimistic scenarios. The cost-effectiveness ratio was 11,000 CHF per year of life gained in the pessimistic scenario. CONCLUSIONS: HAART increases expected survival and health care costs. However, when productivity gains are included, society will probably save costs or pay a low price for substantial health benefits. The study provides strong arguments, from a societal perspective, to continue the current policy of providing unrestricted access to HAART in Switzerland. The presented results also suggest that this policy could be of interest for other developed countries. Decision makers in developed countries where access to HAART is limited should re-evaluate their policy for the benefit of the society at large.

Estimating AIDS-free survival in a severely immunosuppressed asymptomatic HIV-infected population in the era of antiretroviral triple combination therapy. Swiss HIV Cohort Study.

BACKGROUND: Antiretroviral triple combination therapies have been evaluated in randomized controlled trials and cohort studies. Little is known about their impact on asymptomatic, severely immunosuppressed, HIV-infected individuals in a real world population. OBJECTIVES: To describe disease progression in a broad asymptomatic population of HIV-infected individuals with a CD4 count <100 cells/mm3 before and after the introduction of combination triple therapy. DESIGN: Six-month homogenous Markov chain consisting of four recurrent AIDS-free states and one absorbing AIDS state: (1) CD4 count > or =100 cells/mm3, (2) CD4 count 75 to 99 cells/mm3, (3) CD4 count 50 to 74 cells/mm3, (4) CD4 count 0 to 49 cells/mm3, and AIDS. SETTING: Swiss HIV Cohort Study database. PATIENTS: A total of 1027 patients contributed to 2634 pairs of 6-month observations from 1993 to 1995, and 681 patients contributed to 2077 pairs of 6-month observations from 1996 to 1997. MEASUREMENT: AIDS-free survival probabilities and the expected AIDS-free survival time. RESULTS: The expected number of AIDS-free months in a 3-year period was 17 (95% confidence interval [CI], 16-19) for patients starting in state 4 prior to 1996 versus 26 months (95% CI, 24-28) for patients starting in state 4 after 1996. For these two time periods, the corresponding expected numbers of AIDS-free months were 21 (95% CI, 20-22) versus 30 (95% CI, 28-32) for state 3 and 23 (95% CI, 21-24) versus 33 (95% CI, 32-34) for state 2. CONCLUSION: Expected 3-year AIDS-free survival in severely immunosuppressed individuals with CD4 counts <100 cells/mm3 improved significantly between 1993 to 1995 and 1996 to 1997.