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Pharmacoeconomic analysis of 3 treatment strategies for cytomegalovirus retinitis in patients with AIDS |
Griffiths R I, Bleecker G C, Jabs A, Dieterich D T, Coleson L, Winters D, Wolitz R, Steinberg E P |
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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 Treatments for cytomegalovirus (CMV) retinitis in patients with AIDS. Specifically the treatments examined were intravenous ganciclovir (IVG), intravenous foscarnet (IVF),and oral ganciclovir (ORG).
Economic study type Cost-effectiveness analysis and cost-utility analysis.
Study population The study population was a hypothetical cohort of 100,000 patients with AIDS who had untreated CMV.58% of patients were assumed to have unilateral CMV and 42% bilateral CMV.
Setting Hospital and community settings. The economic analysis was conducted in Washington DC, USA.
Dates to which data relate Data on effectiveness were collected from the literature between 1992 and 1995 as well as from other sources for which dates were not stated. The dates associated with the resource data used in the study were not stated, although costs were from 1994 and 1995. The authors stated that 1994 prices were used to report the results.
Source of effectiveness data Effectiveness data were derived from a review of published literature and judgement by an expert panel (opinion).
Modelling A decision analysis model was used to estimate costs and benefits. Monte Carlo simulations were performed for a cohort of 100,000 patients.
Outcomes assessed in the review The outcomes assessed in the review included the probability of death, neutropenia, retinal detachment, contralateral eye movement and need to have switch therapy as a result of using IVG, IVF or in some cases ORG.
Study designs and other criteria for inclusion in the review The authors did not state the study designs and other criteria although all the papers identified dealt with IVF, IVG and ORG. One of the studies identified appears to have been a randomised trial.
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 Five studies were included, including one randomised trial.
Methods of combining primary studies Studies were not combined.
Investigation of differences between primary studies Results of the review The probabilities identified from the literature review were as follows:
neutropenia from IVG 0.34, and from IVF 0.14;
retinal detachment, IVG 0.21, and IVF 0.19;
contralateral eye involvement, IVG 0.17, IVF 0.16 and ORG 0.14;
and switch to alternative therapy IVG 0.11 and IVF 0.46.
The probability of bilateral disease was estimated to be 0.42.
Methods used to derive estimates of effectiveness A panel of five clinicians, expert in treating CMV retinitis, was used to determine the probabilities of other events for IVG, IVF and ORG that had not been determined from the literature review, with the aid of package inserts from the three treatment options. In addition, data were also obtained from the US National Technical Information Service Databank.
Estimates of effectiveness and key assumptions The following probabilities were obtained:
death within 6 months, IVG 0.42, IVF 0.33 and ORG 0.42;
neutropenia from ORG 0.18;
localised catheter infection per patient per year, 0.25 for IVG and IVF and 0.09 for ORG;
bloodstream catheter infection (per patient per year), 0.79 for IVG and IVF and 0.02 for ORG;
retinal detachment for ORG 0.21;
the probability of switching to alternative therapy with ORG, 0.98 within 6 months.
Measure of benefits used in the economic analysis The benefit measures were life years gained and disutility adjusted life years gained. Utility values were derived from previously published data collected from patients with cataracts and values were assigned between 0 and 1. Patients were assumed to have one of 3 levels of visual acuity. The utility value for vision was calculated by multiplying utility associated with visual acuity in the better eye by the probability of having that level of visual acuity initially, at 6 months and at 12 months (interpolations were used for intervening periods).
Direct costs Major quantities were reported separately from the costs. The direct costs associated with medical services identified by the expert panel as being commonly used as part of the treatment for CMV retinitis, including adverse events, were estimated and the associated quantities of resource use reported. The appropriate DRGs for the induction of CMV retinitis therapy, management of catheter-related bloodstream infection, and repair of retinal detachment were identified and national average payments used. Common procedure terminology codes (CPT) were assigned to physician services and then Medicare resource based relative value scale payments were used. Medicare fee schedules were used for laboratory tests and the average wholesale price was applied to treatment options, and treatments for neutropenia and catheter-related infections. New Jersey Medicaid reimbursement schedules were used to cost home nursing visits and supplies relating to the administration of therapy. The results were presented using 1994 prices. Treatment was expected to last for a 12 month period or until death if sooner.
Sensitivity analysis One way sensitivity analyses were conducted and all parameters were varied by 20% above and below the baseline value. In addition, to take account of variations in clinical practice, the length of the induction period was varied from 2 weeks to 3 weeks, having fundus photography every four weeks rather than 8 weeks and an equalisation in length of survival between the groups due to the development of new combination therapy for AIDS was analysed.
Estimated benefits used in the economic analysis The expected unadjusted survival times per patient in the three groups were 40.78 weeks for IVF (95% CI: 40.68 - 40.88), 34.70 weeks for IVG (95% CI: 34.60 - 34.80) and 34.78 weeks for IVG-ORG (95% CI: 34.68 - 34.88). The incremental gain using IVF rather than IVG was 6.08 weeks and compared with IVF-ORG was 6.0 weeks. The expected utility adjusted survival times per patient in the three groups were 31.95 weeks (95% CI: 31.97 - 32.03), 26.86 weeks (95% CI: 26.78 -26.94) and 26.98 weeks (95% CI: 26.90 - 27.06) for IVF, IVG and IVG-ORG groups, respectively. The incremental gain using IVF rather than IVG was 5.09 weeks and compared with IVF-ORG it was 4.97 weeks.
Cost results The expected direct medical costs per patient for a 12 month period (95% CI in parentheses) were $47,918 for IVF (47,783 - 48,053), $38,817 for IVG (38,664 - 38,970) and $32,036 for IVG-ORG(31,915 -32,157). The analysis included the costs of treatment for adverse events and the incremental cost of using IVF in comparison to IVG was $9,101 per patient and in comparison to the IVG-ORG group, $15,882 per patient.
Synthesis of costs and benefits The incremental cost (1994 prices) per unadjusted survival year gained using IVF compared with IVG was $77,838 and $137,644 compared with the IVG-ORG group. The incremental cost per utility adjusted survival year gained using IVF compared with IVG was $92,795 and was $165,836 compared with the IVG-ORG group. The incremental cost per utility adjusted survival year of IVF compared with IVG was moderately sensitive (10% increase or decrease in the cost-effectiveness ratio) to the cost of induction and maintenance therapy with IVF and the cost of maintenance therapy with IVG. It was insensitive to the probability of death, neutropenia, contralateral eye involvement or switching to different therapy. The incremental cost per utility adjusted survival year gained using IVF compared with IVG-ORG was moderately sensitive to the cost of induction and maintenance therapy with IVF and to cost of induction with IVG, and was highly sensitive to the probability of death for IVF and IVG. If the induction period was increased from 2 to 3 weeks, the incremental cost per survival year gained using IVF compared with IVG would increase by 15% to $106,439 and it increased by 7% in comparison to the IVG-ORG group to $177,341. If a new drug does not lead to a difference in the length of survival, IVG-ORG would dominate ($9,000 less expensive) the other two regimens.
Authors' conclusions Treatment for CMV retinitis for AIDS patients is expensive compared with other medical therapy costs. IVG-ORG was the least expensive therapy and had very similar effectiveness to that of IVG. The use of IVF treatment would increase survival expectancy by a small amount but at great cost for utility adjusted life years gained. Adjusting the results for utility (quality of life) changes the outcomes for all three groups by approximately 20%.
CRD COMMENTARY - Selection of comparators The authors provided a justification for their choice of comparators. Both IVF and IVG are well known treatment options for CMV retinitis and the additional alternative, IVG for induction followed by the recently developed oral ganciclovir (ORG) for maintenance therapy, has been approved by the FDA whilst some information on clinical effectiveness was available in the literature. Validity of estimate of measure of benefit The authors did not report the method used to identify the literature from which some of the information on probabilities was derived. It is unknown whether the literature search included all relevant literature related to treatment for CMV retinitis. The authors noted that the study was limited to a 12 month model, as clinical information beyond 12 months was only available for a very small population of patients. The methods by which the expert panel came to its conclusions about probabilities have also not been clearly stated. Sensitivity analysis did demonstrate, however, that results were, in general, robust to 20% changes to base-case parameter values. Validity of estimate of costs As the authors noted, the analysis of costs was limited by the inability to obtain information from one source. In particular they commented on the problems of having to use Medicaid costs (which vary from state to state in the USA) for some costs and Medicare estimates for other costs. The authors noted that the analysis did not consider indirect costs. Cost data may not be applicable outside the State of New Jersey. Other issues The authors noted that the utility scores were derived from a group of older cataract patients who may have significantly different values for visual acuity to a group of terminally ill younger AIDS patients. In addition it would have been useful to have more information on how these scores were estimated for the cataract group. Values should be elicited from the study target population to examine this. As with all economic evaluations that rely heavily on decision modelling and information from the literature, there is a need to conduct well-designed clinical and economic evaluations to further examine the relationship between the different treatments. These evaluations should, as soon as ethically possible, include other treatments which have been identified such as cidofovir and combination therapy with IVF-IVG. Implications of the study There is a need to conduct well-designed economic evaluations prospectively alongside clinical evaluations of treatments for CMV retinitis. Tools need to be developed to measure factors that influence the quality of life for patients with a very short (terminal) life expectancy. Source of funding Financial support from Gilead Sciences Inc, Foster City, California, USA.
Bibliographic details Griffiths R I, Bleecker G C, Jabs A, Dieterich D T, Coleson L, Winters D, Wolitz R, Steinberg E P. Pharmacoeconomic analysis of 3 treatment strategies for cytomegalovirus retinitis in patients with AIDS. PharmacoEconomics 1998; 13(4): 461-474 Indexing Status Subject indexing assigned by NLM MeSH Acquired Immunodeficiency Syndrome /complications /economics; Anti-HIV Agents /economics /therapeutic use; Cytomegalovirus Retinitis /drug therapy /economics /physiopathology; Decision Support Techniques; Economics, Pharmaceutical; Humans AccessionNumber 21998008163 Date bibliographic record published 31/08/1999 Date abstract record published 31/08/1999 |
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