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Model for simulation of HIV/AIDS and cost-effectiveness of preventing non-tuberculous mycobacterial (MAC)-disease |
Hoffmann T, Brunner H |
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Record Status This is a critical abstract of an economic evaluation that meets the criteria for inclusion on NHS EED. Each abstract contains a brief summary of the methods, the results and conclusions followed by a detailed critical assessment on the reliability of the study and the conclusions drawn. Health technology Three treatments for the prevention of non-tuberculous mycobacterial (MAC)-disease in patients with human immunodeficiency virus or acquired immune deficiency syndrome (HIV/AIDS) were examined. The treatments were clarithromycin, azithromycin and rifabutin. Clarithromycin was given at a dosage of 1,000 mg/day, azithromycin at 1,250 mg/week, and rifabutin at 300 mg/day.
Type of intervention Primary and secondary prevention.
Economic study type Cost-effectiveness analysis.
Study population The study population comprised a hypothetical cohort of patients with HIV/AIDS with 50 or fewer CD4 cells/microL blood.
Setting The setting was secondary care and a hospital. The economic study was carried out in Germany.
Dates to which data relate The effectiveness data were derived from studies published between 1993 and 1998. The resource use data were mainly derived from a study published in 1996. The price year was not reported.
Source of effectiveness data The effectiveness evidence was derived from published studies.
Modelling A Markov model was constructed to assess the costs and benefits of the three preventive treatments, compared with no prophylaxis, in a cohort of patients with HIV/AIDS. The time horizon of the model was lifetime, while the cycle length was one month. A simplified structure of the model was reported. Three different health states were considered. Specifically, chronic, acute and death. A patient entered the model in the chronic disease state with a specific CD4 cell count. In the next cycle, the patient could either remain in the chronic state or enter the acute state, where the patient remained for only one cycle (tunnel state), after which either the infection was treated (and the patient returned to the chronic state) or treatment failed (and the patient died). Patients could also die in the chronic disease state.
Outcomes assessed in the review The health outcomes assessed from the literature were the transition probabilities across health states, and the efficacy of the three compounds. Transition probabilities were estimated from data on decline in CD4 count, rates of infection, and mortality rates.
Study designs and other criteria for inclusion in the review It appears that the primary studies were identified selectively rather than by means of a systematic review of the literature. The transition probabilities came from a German register and these data were validated by comparison with other published studies. Details on the sources of efficacy of prophylactic treatments were not provided.
Sources searched to identify primary studies Criteria used to ensure the validity of primary studies Methods used to judge relevance and validity, and for extracting data Number of primary studies included Four primary studies provided clinical data for the decision model.
Methods of combining primary studies The primary estimates were not combined since each study provided a series of data.
Investigation of differences between primary studies Results of the review All rates were estimated for a 30-day period, which was consistent with the cycle length of the model.
The rate of CD4 cell decline in patients with high cell count was 0.0105.
The rate of acute MAC infection (primary infection) was 0 in patients with a high cell count and 0.0067 in patients with a low cell count.
The rate of MAC infection relapse was 0.
The rate of acute non-MAC infection was 0.0171 in patients with a high cell count and 0.0353 in patients with a low cell count.
The mortality rate in patients with a high cell count was 0.0799 for acute non-MAC infection and 0.0016 in the chronic state (no history of MAC infection).
The mortality rate in patients with a low cell count was 0.0645 with acute MAC infection, 0.1338 with acute non-MAC infection, 0.0239 in the chronic state with no history of MAC infection, and 0.06894 in the chronic state with history of MAC infection.
The efficacy of prophylactic treatments (representing the reduction in probability of transition from a chronic state to an acute state of MAC infection) was 0.72 with clarithromycin, 0.63 with azithromycin, and 0.51 with rifabutin.
Measure of benefits used in the economic analysis The summary benefit measure used was expected survival. This was obtained from the decision model. Discounting was not applied in the base-case.
Direct costs The analysis of the costs was carried out from the perspective of the health insurance system. A breakdown of the costs included in the analysis was not provided, as the costs were presented as macro-categories associated with specific health states. Inpatient and drug costs appear to have been considered. The unit costs were not presented separately from the quantities of resources used. Resource use was estimated on the basis of a published study and experts' opinions. The costs came from average wholesale prices for drugs and official daily charges for other items. No discounting was applied in the base-case. The price year was not reported.
Statistical analysis of costs The costs were treated deterministically in the base-case.
Indirect Costs The indirect costs were not included in the economic evaluation.
Sensitivity analysis Sensitivity analyses were carried out, presumably to assess the robustness of the base-case results to variations in some model inputs (costs and efficacy) and to consider the impact of discounting. A further scenario in which protease inhibitors were available was also considered (they were not available in the base-case due to lack of data). The ranges of values used in the sensitivity analyses are likely to have been set by the authors. A threshold analysis was also undertaken.
Estimated benefits used in the economic analysis In the base-case, expected survival was 39.42 months with no prophylaxis, 41.63 months with azithromycin, 41.99 months with clarithromycin, and 41.16 months with rifabutin.
In the protease inhibitors scenario, expected survival was 69.56 months with no prophylaxis, 74.25 months with azithromycin, and 75.03 months with clarithromycin (rifabutin was excluded because it was dominated in the base-case).
Cost results In the base-case, the expected costs were EUR 31,678 with no prophylaxis, EUR 34,167 with azithromycin, EUR 41,564 with clarithromycin, and EUR 42,446 with rifabutin.
In the protease inhibitors scenario, the expected costs were EUR 97,604 with no prophylaxis, EUR 106,323 with azithromycin, and EUR 121,005 with clarithromycin (rifabutin was excluded because it was dominated in the base-case).
Synthesis of costs and benefits An incremental cost-effectiveness ratio was calculated to combine the costs and benefits of the alternative compounds in comparison with no prophylaxis.
The incremental cost per life-year gained was EUR 13,515 with azithromycin, EUR 46,152 with clarithromycin, and EUR 74,268 with rifabutin. The analysis showed that rifabutin was dominated since it was both less effective and more expensive than azithromycin and clarithromycin.
The sensitivity analysis suggested that azithromycin remained a cost-effective strategy even when the price of clarithromycin was reduced. The application of a 5% discount rate to both the costs and benefits increased the incremental cost-effectiveness ratios, but did not alter the conclusions of the base-case analysis. The same results were observed in the protease inhibitor scenario, in which azithromycin remained the most cost-effective prophylactic option.
Authors' conclusions Azithromycin was the most cost-effective preventive treatment against non-tuberculous mycobacterial (MAC) infections in patients with human immunodeficiency virus or acquired immune deficiency syndrome (HIV/AIDS) in Germany.
CRD COMMENTARY - Selection of comparators The rationale for the choice of the comparators was clear. Three compounds available for prophylaxis in patients with HIV/AIDS were considered and were compared with no prophylaxis. The dosages were appropriately reported. The more realistic scenario including protease inhibitors was also considered. You should decide whether they are valid comparators in your own setting.
Validity of estimate of measure of effectiveness The effectiveness evidence was derived from published sources. However, it was not stated whether a systematic review of the literature was undertaken, and the primary studies appear to have been identified selectively. In general, few details were provided and this made it difficult to assess the validity of the primary sources. Further, the issue of the homogeneity of the primary studies was not addressed. This appears to have been a key element of the analysis, given that the efficacy of the three drugs was obtained from three different studies. Finally, only limited sensitivity analyses were performed.
Validity of estimate of measure of benefit The summary benefit measure was appropriate for the disease considered in the study. In addition, it has the further advantage of being comparable with the benefits of other health care interventions. The use of a discount rate was investigated in the sensitivity analysis. The impact of the prophylactic strategies on quality of life was not considered.
Validity of estimate of costs The costs included were consistent with the perspective adopted in the study. However, only few direct medical costs strictly associated with the interventions under examination were considered. Other costs related to the care of patients with HIV/AIDS were not taken into consideration, and the impact on the results of including such costs was not clear. The source of the data was not reported clearly for all items, and there was limited information on the unit costs. Resource use was based on assumptions and clinical patterns in the authors' setting. The price year was not explicitly stated, which will hinder reflation exercises in other time periods. The cost estimates were varied in the sensitivity analysis.
Other issues The authors did not compare their findings with those from other studies. The issue of the generalisability of the study results to other settings was not explicitly addressed, but some sensitivity analyses were carried out. This, to some extent, will enhance the external validity of the study. The analysis referred to patients with HIV/AIDS and this was reflected in the authors' conclusions. The authors pointed out the strength of the model used in the study.
Implications of the study The study results would appear to support the use of prophylactic azithromycin for the prevention of MAC infections in patients with HIV/AIDS. The authors noted that German health authorities should develop robust cost and efficacy data.
Bibliographic details Hoffmann T, Brunner H. Model for simulation of HIV/AIDS and cost-effectiveness of preventing non-tuberculous mycobacterial (MAC)-disease. European Journal of Health Economics 2004; 5: 129-135 Other publications of related interest Pierce M, Crampton M, Henry D, et al. A randomized trial of clarithromycin as prophylaxis against disseminated Mycobacterium avium complex infection in patients with advanced acquired immunodeficiency syndrome. N Engl J Med 1996;335:384-91.
Havlir DV, Dube MP, Sattler FR. et al. Prophylaxis against disseminated Mycobacterium avium complex with weekly azithromycin, daily rifabutin, or both. N Engl J Med 1996;335:392-8.
Nightingale SD, Cameron DW, Gordin FM, et al. Two controlled trials of rifabutin prophylaxis against disseminated Mycobacterium avium complex infection in AIDS. N Engl J Med 1993;329:828-3.
Indexing Status Subject indexing assigned by NLM MeSH Acquired Immunodeficiency Syndrome /complications /economics; Anti-Bacterial Agents /economics /therapeutic use; Azithromycin /economics /therapeutic use; CD4 Lymphocyte Count; Clarithromycin /economics /therapeutic use; Cost-Benefit Analysis; Drug Therapy, Combination; Health Care Costs; Humans; Models, Economic; Mycobacterium avium-intracellulare Infection /etiology /prevention & Protease Inhibitors /administration & Quality-Adjusted Life Years; Rifabutin /economics /therapeutic use; control; dosage /therapeutic use AccessionNumber 22004008326 Date bibliographic record published 31/07/2006 Date abstract record published 31/07/2006 |
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