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Should resistance testing be performed for treatment-naive HIV-infected patients: a cost-effectiveness analysis |
Sax P E, Islam R, Walensky R P, Losina E, Weinstein M C, Goldie S J, Sadownik S N, Freedberg K A |
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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 The authors studied whether genotype resistance testing should be performed for treatment-naive patients infected with the human immunodeficiency virus (HIV). Resistance testing took the form of a blood test and was compared with no resistance testing.
Type of intervention Secondary screening of HIV-infected patients to assess whether HIV is resistant to some potential treatments.
Study population The target study population comprised a cohort of HIV-infected, antiretroviral-naive patients. The hypothetical study sample comprised chronically ill HIV-infected patients with characteristics similar to the general HIV population as reported in a published study.
Setting The setting was primary care. The economic study was carried out in the USA.
Dates to which data relate The effectiveness data were obtained from studies published between 1995 and 2004. The costing data were obtained from studies and reports published between 1982 and 2001. The price year was 2001.
Source of effectiveness data The effectiveness data were derived from a review and synthesis of published studies, supplemented with the authors' modelling assumptions.
Modelling The authors used a published model to simulate the progression of HIV and its associated outcomes. Further details of this model, including its structure, data and assumptions, are reported elsewhere (Weinstein et al., Freedberg et al. 1998 and 2001, Paltiel et al. 2005, see 'Other Publications of Related Interest' below for bibliographic details). The model tracked individual patient histories in 1-month cycles. The three health states included were chronic infection, acute clinical event and death. The model tracked the length of time any patient spent in each of these states, the time spent receiving therapy, and duration of survival and quality-adjusted survival. Data on the monthly risks of HIV disease progression, the probabilities of acute opportunistic infection, and the rates of death due to other causes were incorporated.
Outcomes assessed in the review The review assessed data for input into the Markov Model. Outcomes included the prevalence of antiretroviral resistance among treatment-naive patients, the likely virologic suppression rate of the first through fifth sequential lines of therapy, the proportion of the untested population receiving efavirenz-based therapy, and the efficacy of first-line therapy. The authors do not appear to have carried out a systematic review of the literature because of the modelling nature of the study, and instead selected sources relevant to their model.
Study designs and other criteria for inclusion in the review The review included data from clinical trials, observational cohort studies, surveillance studies of primary resistance, and a published model of HIV disease.
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 Seventeen studies were included in the review.
Methods of combining primary studies Where appropriate, the authors used narrative methods to combine the results from the primary studies. A model input seems to have been derived from a single source in many cases.
Investigation of differences between primary studies The authors acknowledged that there was a lack of published data and discussed some differences between the studies. They then used a sensitivity analysis to explore the impact of these differences.
Results of the review The prevalence of antiretroviral resistance among treatment-naive patients was 8.3%.
The authors reported a table of results containing the likely virologic suppression rate of the first through fifth sequential line of therapy. These data are not reproduced here.
The proportion of the untested population receiving efavirenz-based therapy was 75%.
The efficacy of first-line therapy ranged from 19 to 75%.
Methods used to derive estimates of effectiveness The review was supplemented with modelling assumptions.
Estimates of effectiveness and key assumptions The authors assumed that nucleoside reverse-transcriptase inhibitor (NRTI) resistance would be a component of multi-drug resistance, and that patients without resistance could receive five sequential lines of treatment.
Measure of benefits used in the economic analysis The summary measures of health benefit used were the quality-adjusted life-years and life-months (QALYs and QALMs, respectively). Health-related quality of life data were derived from the HIV Cost and Services Utilization Study, while utility weights applicable to AIDS/HIV patients were taken from a published study (Schackman et al. 2002, see ,Other Publications of Related Interest- below for bibliographic details). Future life-years were discounted at a rate of 3%.
Direct costs The authors used the AIDS Costs and Services Utilization Survey and the HIV Costs and Services Utilization Survey to estimate the direct costs of treatment for routine medical care and for acute illness. Charge data were converted to cost data using a cost-to-charge ratio. The drug costs were taken from the 2001 Drug Topics Red Book and the cost of a resistance test was based on data from the Brigham and Women's Hospital. The costs were presented in 2001 prices and were discounted at an annual rate of 3%.
Statistical analysis of costs The costs were treated deterministically.
Indirect Costs There was no evidence that the indirect costs were incorporated into the analysis, despite the perspective being reported as societal.
Sensitivity analysis Numerous sensitivity analyses, including one-way and two-way analyses, were carried out. These focused on exploring the impact of rates of resistance, the virologic suppression rate, and costs of resistance testing.
Estimated benefits used in the economic analysis The mean quality-adjusted life expectancy was 168.3 months without resistance testing and 169.3 months with resistance testing (difference 1.0 QALMs).
Patients with non-NRTI- and NRTI-resistant strains benefited most from resistance testing, with a mean gain of 14.1 QALMs (non-NRTI) and 13.8 QALMs (NRTI) compared with no testing.
Patients with protease inhibitor-resistant strains had a mean gain of 4.9 QALMs.
Cost results The mean total discounted lifetime costs were $336,600 without resistance testing and $338,600 with resistance testing (difference $2,000).
Synthesis of costs and benefits The incremental cost of testing per QALY gained was $23,900 compared with no testing.
When the prevalence of resistance was varied from 0.25 to 10.0%, the estimated cost-effectiveness ranged from $175,400 to $23,100 per QALY gained.
The cost-effectiveness was relatively robust to changes in the cost of testing and the efficacy of resistance testing.
Authors' conclusions Genotype resistance testing should be performed for all patients with a newly diagnosed human immunodeficiency virus (HIV) infection in the USA.
CRD COMMENTARY - Selection of comparators The authors compared genotype testing against no genotype testing in order to estimate the clinical benefits and costs associated with using resistance testing to guide treatment choices. No testing was the natural choice of comparator to answer this clinical question. It also seems to have represented current practice in the authors' setting for treatment-naive patients.
Validity of estimate of measure of effectiveness The authors did not undertake a systematic review of the literature. Their study centred on a decision model and sources were selected to inform the parameters of the model. The authors clearly reported that the model was from a published source and readers were referred to the source for further details. No details of the search strategy were reported, nor were the methods used to ensure the validity of the primary studies. The quality of the input data might therefore be open to question. The authors explained how the primary data were combined, but more information would have benefited the reader by improving their understanding. Sensitivity analyses were used to explore the impact of differences in the primary studies, as well as underlying uncertainty in the true values of parameter inputs.
Validity of estimate of measure of benefit QALYs and QALMs were used as the summary measures of health benefit. These measures were estimated via a model and were informed by utilities from a published study. The use of such broad measures enables wide comparisons with a range of other health-related technologies.
Validity of estimate of costs The authors reported that a societal perspective was adopted and included the direct costs of providing resistance testing that were relevant to this perspective. However, for a true societal perspective, the authors should also have estimated wider costs such as the economic impact of increased or lost time at work engaging in economically productive activities. The extent to which the inclusion of these costs would have influenced the results and conclusions was unclear. The authors could have broken down their cost estimates to provide an improved understanding of the key cost-drivers within the model.
Other issues The authors were able to make some broad comparisons of their cost-effectiveness results, stating that their results fell within the range of other commonly accepted HIV interventions. However, they did not make comparisons with other studies exploring similar clinical questions; this might have been due to a general lack of evidence in this area. The generalisability of the study was considered when the authors decided to incorporate national HIV costs and usages, and was further improved by sensitivity analyses exploring the impact of differing parameter values. The authors presented their results clearly, although they could have given a more detailed breakdown of the costs. The conclusions were an accurate reflection of the results presented and were appropriate to the study question. Several limitations were presented. These included the heterogeneous nature of the sources of effectiveness data, and not specifically examining the development of new drug classes.
Implications of the study The authors suggested "genotype resistance testing should be performed for all patients with newly diagnosed HIV infection in the United States, with the results used to guide the choice of antiretroviral regimen when treatment is indicated".
Source of funding Funded by the National Institute of Allergy and Infectious Diseases and the Centers for Disease Control and Prevention.
Bibliographic details Sax P E, Islam R, Walensky R P, Losina E, Weinstein M C, Goldie S J, Sadownik S N, Freedberg K A. Should resistance testing be performed for treatment-naive HIV-infected patients: a cost-effectiveness analysis. Clinical Infectious Diseases 2005; 41(9): 1316-1323 Other publications of related interest Weinstein MC, Goldie SJ, Losina E, et al. Use of genotype resistance testing to guide HIV therapy: clinical impact and cost-effectiveness. Ann Intern Med 2001;134:440-50.
Freedberg KA, Losina E, Weinstein MC, et al. The cost-effectiveness of combination antiretroviral therapy for HIV disease. N Engl J Med 2001;344:824-31.
Freedberg KA, Scharfstein JA, Seage GR, et al. The cost-effectiveness of preventing AIDS-related opportunistic infections (published erratum appears in JAMA 1999;281:1989). JAMA 1998;279:130-6.
Paltiel AD, Weinstein MC, Kimmel AD, et al. Expanded screening for HIV in the United States - an analysis of cost-effectiveness. N Engl J Med 2005;352:586-95.
Schackmann BR, Goldie SJ, Freedberg KA et, al. Comparison of health state utilities using community and patient preference weights derived from a survey of patients with HIV/AIDS. Med Decis Making 2002;22:27-38.
Indexing Status Subject indexing assigned by NLM MeSH Adult; Anti-Retroviral Agents /pharmacology /therapeutic use; Cost-Benefit Analysis; Drug Resistance, Viral; Female; Genotype; HIV /drug effects /genetics; HIV Infections /drug therapy; Humans; Male; Microbial Sensitivity Tests /economics /utilization AccessionNumber 22005001844 Date bibliographic record published 30/06/2006 Date abstract record published 30/06/2006 |
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