AT1 receptor blockers--cost-effectiveness within the South African context.

OBJECTIVES: Hypertension is a leading chronic disease in South Africa, Significant mortality results from this condition and from stroke and ischaemic heart disease in which hypertension plays a major role. The objective of this study was to evaluate the evidence for the clinically effective and cost-effective treatment of hypertension, given that the clinician has decided to administer an AT1 receptor blocker. METHODOLOGY: A cost-effectiveness analysis was undertaken from the perspective of the funder of health care in the private sector. A predetermined protocol defined the study scope, the comparators (candesartan, losartan, valsartan and irbesartan) and the inclusion criteria for peer-reviewed data. Data for the clinical efficacy of the comparators, measured as the reduction (mmHg) in sitting diastolic blood pressure (SDBP) achieved, were extracted, statistically assessed and reported. The combinability of the data from different clinical trials was confirmed using analyses of variance. A pharmacoeconomic model was developed by combining these clinical results with South African retail prices and testing the results at a 95% confidence level. RESULTS: Significant difference in clinical effectiveness was found among the comparators, with the following mean reductions in SDBP observed: candesartan 10.57, irbesartan 9.07, losartan 8.89 and valsartan 7.11 mmHg. Candesartan was found to be significantly more effective than losartan. Valsartan was found to be less effective than the other 3 comparators. No significant difference was found between irbesartan and either candesartan or losartan. The reduction in SDBP per R100 spent indicated that candesartan was more cost-effective than the other comparators, among which there were no significant differences. Incremental savings of R5.0 million annually could be achieved by the funders of private health care for every 100,000 successfully treated patients using candesartan. CONCLUSION: Significant differences exist in both the clinical and cost-effectiveness measures used in this study for the comparators. The findings from the analysis will be valuable in decision-making processes for both the funders and providers of health care. This analysis can be enhanced further by the inclusion of additional clinical benefits and long-term health outcomes when the relevant data become available.

A South African pharmaco-economic analysis of the Acute lnfarction Ramipril Efficacy (AIRE) Study.

OBJECTIVES: Heart failure (HF) is a serious, prevalent health condition in industrialised countries where the incidence has been on the increase. The economic repercussions are costly, and therefore cost-effective medication is important in the overall management of the condition. It has been shown that angiotensin-converting enzyme (ACE) inhibitors are clinically effective in the management of HF. Ramipril has been shown to reduce mortality and the probability of hospitalisation in post-myocardial infarction (MI) patients. Internationally, the use of this drug has proved to be cost-effective. The objective of this study was to investigate the economic implications of using ramipril in South Africa for post-MI patients with HF. METHODOLOGY: An incremental cost-effectiveness analysis was performed comparing the use of ramipril and placebo in post-MI patients with HF who were receiving standard therapy. The economic impacts included drug acquisition costs and savings on hospitalisation; these were evaluated based on the clinical benefits of using ramipril in terms of life-years gained (LYG). The cost-utility of the use of ramipril was determined to provide an incremental cost per quality-adjusted life-year (QALY). Sensitivity analyses were performed on the major economic variables; discounting of future costs and savings was performed at rates of 0%, 5 % and 10 %. RESULTS: The use of ramipril results in an incremental cost/LYG of R16 808 and a total incremental cost per patient per month of R107 over 3.8 years. When the quality of life of the patients is taken into account, the cost-utility analysis shows an incremental cost/QALY of R21 382 for those younger than 65 years of age and R18 029 for those older than 65 years. The pharmaco-economic model was robust and consistent when tested at the extremes of the major variables, including costs, savings and discount rates. CONCLUSION: The results indicate that it is cost-effective to administer ramipril in addition to standard therapy for post-MI patients with HF in South Africa.

The cost-effectiveness of isotretinoin in the treatment of acne. Part 1. A meta-analysis of effectiveness literature.

OBJECTIVES: This paper reports the results of a meta-analysis of isotretinoin treatment in moderate to severe acne. It forms part of a comprehensive investigation into the cost-effective treatment of acne in South Africa and as such establishes the clinical foundation for an economic model of acne management. This foundation includes an evaluation of the daily dosages, treatment durations, success rates, clinical effectiveness and relapse rates reported in published trials since 1981. METHODOLOGY: A predetermined protocol for the study established the scope, appropriate inclusion and exclusion criteria for peer-reviewed data, and the statistical rigour that would be applied to the selected data. Following an extensive literature search, data reflecting the effectiveness of isotretinoin were extracted, statistically assessed, described and reported. The combinability of the data was confirmed using analyses of variance and chi-square tests, as applicable. RESULTS: Isotretinoin consistently proved to be a highly effective agent in the treatment of moderate to severe acne vulgaris. The response rate determined by the meta-analysis indicated a clinical cure in 84.22% to 86.71% of patients treated. From the data considered, the average treatment duration was calculated to be 17.9 weeks (4 months). The relapse rate was low (21.45%) and dose-dependent. Optimal results were achieved by treating patients with a daily dose of 1 mg/kg and treating to a target cumulative dose of 120 mg/kg over the treatment duration. CONCLUSION: The results of this meta-analysis support the continued use of isotretinoin in the treatment of acne. The results are important in the field of pharmaceutical benefit management where they will assist in the optimal management of this health condition. The results will be used to develop a pharmaco-economic model to evaluate the various treatment regimens used for acne in South Africa.

The cost-effectiveness of isotretinoin in the treatment of acne. Part 2. A chronic medication plan profiling study.

OBJECTIVES: Aspects of current clinical practice, needed for a pharmaco-economic model of isotretinoin, were determined from an acne-profiling study on chronic medication plan data. The patient sample was analysed as a whole and as two subgroups, representing isotretinoin and oral antibiotic patients. The study focused on the prevalence of the condition, patient age and gender distributions, and pharmacotherapeutic patterns and costs. METHODOLOGY: Anonymous patient records from the Pharmaceutical Benefit Management (Pty) Ltd, Cape Town, chronic medication plan were screened and analysed using descriptive and inferential statistical methods. For all hypothesis tests, the significance level (alpha) was set a priori at 5% (0.05). In order to determine the distribution of costs among patient groups, cost-concentration curves were constructed. RESULTS: A total of 5,198 patient records were analysed, representing 3,546 acne patients (2.7% of applicants to the plan). The majority of patients were female (72.2%, median age 23 years), with male patients treated at a younger age (median age 19 years). The cyproterone/oestrogen combination was found to be the most frequently prescribed agent (25.2% of script items), followed by isotretinoin (15.6%). The oral antibiotics as a group accounted for 24.9% of script items, the leading agents being minocycline (10.1%) and doxycycline (7.1%). Isotretinoin (44.1%) represented the greatest expense, followed by hormonal therapies (24.7%) and oral antibiotics (16.7%). Female isotretinoin patients (55.1%) were older (median age 25 years), while the male patients were of an equivalent age to the collective sample. Patients treated with oral antibiotics represented the youngest group of patients (median age 20 years), with 57.8% being female. The annual pharmacotherapy expense per patient on oral antibiotics was R1 971.81 compared with R2 670.20 for all patients, and R6 140.81 for the isotretinoin group. For each of these groups there was an uneven cost distribution among patients. CONCLUSION: The treatment of acne represents a significant burden to funders, estimated at R7.2 million per 100,000 beneficiaries. The distinct age and gender distribution patterns, together with the uneven distribution of costs among patients, provide valuable information for the treatment and management of the condition. This information indicates that the introduction of clinically based, focused management principles supported by sound pharmaco-economic arguments will be required to manage acne effectively.

The cost-effectiveness of isotretinoin in the treatment of acne. Part 3. A cost-minimisation pharmaco-economic model.

OBJECTIVES: The cost-effectiveness of systemic isotretinoin therapy in the treatment of moderate to severe acne was assessed in a comparative cost-minimisation analysis. Systemic isotretinoin at the recommended daily dose of 1 mg/kg (cumulative dose of 120 mg/kg) was compared with: (i) oral antibiotics taken as chronic medication; (ii) a combination of chronic oral antibiotics and anti-androgen therapy; and (iii) isotretinoin prescribed only after two failed courses of oral antibiotics, as per South African guidelines. The perspective taken was that of the funder of health care, and the resources used were funder charges as a proxy for costs. METHODOLOGY: Statistical and epidemiological data as well as relevant costs from the previously reported meta-analysis and profiling study for acne therapy were used as the clinical basis for the construction of a cost-minimisation model. Additional costs were sourced from published pharmaceutical retail prices and professional rates. The South African treatment guidelines were used to define the frequencies associated with physician visits and pathology testing. Standard statistical methods were applied, as appropriate. From the above, a modified Markov process was used to model the costs associated with the four comparator treatment regimens over a period of 120 months. Suitable clinical and economic endpoints were defined so that comparison could be made between regimens. RESULTS: Assuming a relapse rate of 21.45%, it was found that isotretinoin therapy compares favourably with the other regimens. After 50 and 35 months, systemic isotretinoin cumulative costs were less than those incurred in oral antibiotic and oral antibiotic/anti-androgen therapy, respectively. For the stepped therapy of oral antibiotics followed by systemic isotretinoin, these break-even periods were 56 and 39 months, respectively. The cost per successfully treated patient receiving isotretinoin was R8941. This compares well with the cost for those patients receiving chronic oral antibiotics, which after 5 years amounted to R10 428 per patient. Sensitivity analyses proved these findings to be robust to variations in the isotretinoin relapse rate, and the cost of oral antibiotic therapy and the concomitant use of topical therapies. CONCLUSION: From the cost-minimisation model it is clear that where systemic isotretinoin is clinically indicated, the sooner such therapy is initiated the more cost-effective the outcome will be. If isotretinoin is prescribed on diagnosis of moderate to severe acne, then the cost of treatment is significantly reduced in the long term when compared with standard chronic oral antibiotic therapy.