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Economic evaluation of treatment administration strategies of ganciclovir for cytomegalovirus retinitis in HIV/AIDS patients in Thailand: a simulation study |
Teerawattananon K, Iewsakul S, Yenjitr C, Ausayakhun S, Yenjitr W, Mugford M, Teerawattananon Y |
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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 study compared different strategies for the administration of ganciclovir:
a combination of intravenous (IV) for the induction phase and oral (OR) for the maintenance phase (IV/OR);
intravitreal injection (IVT); and
intraocular implantation (IMP).
The 'do-nothing' approach was used as a comparator.
Study population As this was a modelling study, the target population comprised HIV/AIDS patients suffering from either bilateral or unilateral CMVR. However, no further details of the target population were provided and no specific inclusion criteria were reported.
Setting The setting of the study was secondary care. The economic study was carried out in Thailand.
Dates to which data relate The baseline clinical effectiveness data were derived from studies published between 1991 and 2005. The resource use data were collected from a cohort of patients between October and December 2005. The cost estimates were obtained from a prospective survey conducted between October and December 2005 by the authors and from studies published in 2001 and 2004. All costs were reported for the price year 2005.
Source of effectiveness data All of the clinical parameters included in the model were reported in detail. The most important clinical parameters associated with each of the treatment administration strategies were:
the probability of developing bilateral CMVR in unilateral CMVR patients,
extraocular CMV infection with IVT and IMP,
intraocular complications in one or both eyes in bilateral and unilateral patients,
the probability of developing endophthalmitis,
retinal detachment in one or both eyes, and
the probability of developing sepsis with IV/OR.
Modelling The authors used two separate decision tree models to model disease progression of unilateral and bilateral CMVR patients. Details of the model, such as the time horizon, the health states, relevant modelling assumptions and data on probabilities, were presented in full. It was reported that five experts from the authors' setting (ophthalmologists with expertise in the treatment of CMVR in HIV/AIDS patients) validated the two models.
Sources searched to identify primary studies The clinical effectiveness data were derived from published studies. However, study designs were not discussed in the current paper, making it difficult to assess the validity of the estimates used.
Methods used to judge relevance and validity, and for extracting data The authors reported that a systematic review of the literature was conducted for the main effectiveness estimates. The inclusion criteria were specified and the methods of the review were reported in full. The probability of having CMVR in the other eye was based on a meta-analysis, applying a Bayesian fixed-effect approach, of three studies. The authors did not report the results of the systematic review, and the study designs of the studies included in the review were not discussed.
Measure of benefits used in the economic analysis The measure of benefit used was the quality-adjusted life-years (QALYs). These were estimated using a modelling approach. The utility weights were obtained from four published studies and were augmented by authors' assumptions and data from a cohort of 362 patients receiving IVT in the authors' setting (Chiangmai University Hospital). The authors' assumptions and utility scores were reported in full. The benefits were discounted at an annual rate of 3.5% in all cases where life expectancy extended beyond 1 year.
Direct costs The health care costs included in the analysis were IVT per injection, operation and maintenance costs for IMP, induction cost for IV, monthly maintenance cost of oral ganciclovir, treatment of endophthalmitis, retinal detachment, CMV infection in other organs, and sepsis. Direct non-health care costs included travelling costs (transportation and food) per visit. Resource use was determined using a micro costing methodology. Structured questionnaires were used to interview a cohort of 76 patients who received treatment for CMVR at two different centres (Chiangmai University Hospital and Chingkhum Hospital). The unit costs were derived either from published literature or from the authors' setting and were reported in full. Costs identified from earlier than 2005 were converted to 2005 prices using the Consumer Price Index. All costs were reported for the price year 2005 and were assumed to be incurred for less than 1 year, making discounting irrelevant.
Statistical analysis of costs No statistical analyses of the costs were conducted.
Indirect Costs The productivity costs included in the analysis were for patients or relatives' income lost due to sick leave or hospital visits. Resource use was determined using a micro costing methodology, while unit costs were based on structured interviews of a cohort of 76 patients. The costs were reported for the price year 2005 and discounting was not performed.
Sensitivity analysis Parameter uncertainty was investigated through probabilistic sensitivity analysis using second-order Monte Carlo simulation. All the parameters in the model were assigned prior probability distributions which were reported in full. Details of the rationale for the selection of distributional assumptions were provided in a separate study (Briggs 2000, see 'Other Publications of Related Interest' below for bibliographic details).
Estimated benefits used in the economic analysis Incremental benefits were reported for unilateral and bilateral patients separately. The 'do nothing' approach was compared with IVT, IVT was compared with IV/OR and, finally, IV/OR was compared with IMP.
From a societal perspective for unilateral CMVR patients, the QALYs gained ranged from 0.03 for moving from IV/OR to IMP for patients not receiving ART to 0.22 QALYs gained when moving from 'do nothing' to IVT for patients not receiving ART.
For bilateral CMVR patients, the QALYs gained ranged from 0.03 for moving from IV/OR to IMP for patients not receiving ART to 1.01 QALYs gained for moving from 'do nothing' to IVT for patients receiving ART.
Moving from IV/OR to IMP did not result in any benefits gained for any group of patients.
When the perspective of the health care system was adopted, the estimated benefits reported did not vary significantly from those reported for the societal perspective.
Cost results The incremental cost results per patient were reported.
From a societal perspective, moving from 'do nothing' to IVT resulted in an incremental cost that ranged from THB 3,700 for unilateral patients with ART to THB 48,000 for bilateral patients without ART.
Moving from IVT to IV/OR resulted in an incremental cost that ranged from THB 20,000 for unilateral patients without ART to THB 15,000 for bilateral patients with and without ART.
Moving from IV/OR to IMP resulted in an incremental cost that ranged from THB 20,000 for unilateral patients with ART to THB 55,000 for bilateral patients with ART.
From the perspective of the health care provider, the incremental costs when moving from 'do nothing' to IVT were THB 13,000 for unilateral patients and THB 18,000 for bilateral patients.
Moving from IVT to IV/OR resulted in incremental costs of THB 31,000 and 32,000 for unilateral patients with and without ART, respectively, and THB 26,000 and THB 27,000 for bilateral patients with and without ART.
Moving from IV/OR to IMP resulted in incremental costs of THB 33,000 and THB 32,000 for unilateral patients with and without ART, respectively, and THB 66,000 for bilateral patients with and without ART.
Synthesis of costs and benefits An incremental cost-effectiveness analysis was performed. Only non-dominated strategies are reported here.
From a societal perspective, IVT resulted in an incremental cost-effectiveness ratio (ICER) that ranged from THB 173,000 to THB 183,000 per QALY gained for unilateral and bilateral patients without ART compared with 'do nothing'.
IV/OR resulted in an ICER that ranged from THB 121,000 per QUALY gained for bilateral patients with ART to THB 435,000 per QALY gained for bilateral patients without ART compared with IVT.
IMP resulted in an ICER above THB 628,000 per QALY gained compared with IV/OR.
From the perspective of the health care provider, IVT resulted in an ICER that ranged from THB 18,000 to THB 68,000 per QALY for bilateral patients with and without ART, respectively, compared with 'do nothing'.
IV/OR resulted in an ICER that ranged from THB 233,000 per QALY for bilateral patients with ART to THB 639,000 for unilateral patients without ART compared with IVT.
IMP resulted in an ICER above THB 932,000 per QALY gained when compared with IV/OR.
The probabilistic sensitivity analysis demonstrated that, from a societal perspective at a willingness-to-pay (WTP) that ranged from THB 180,000 to THB 400,000 per QALY gained, IVT was the preferred option for bilateral and unilateral patients with and without ART. IV/OR became the preferred option if the WTP ranged from THB 400,000 to THB 780,000; above the latter threshold IMP became the preferred option.
From the perspective of the health care provider, at a WTP threshold that ranged from THB 240,000 to THB 640,000, IVT became the preferred option for unilateral and bilateral patients with and without ART.
Authors' conclusions Based on the information in the study, the authors concluded that the administration of ganciclovir by intravitreal injection (IVT) to patients with unilateral or bilateral cytomegalovirus retinitis (CMVR) "represents good value for money". The provision of antiretroviral therapy (ART) improved the cost-effectiveness of all CMVR ganciclovir treatment options. All treatment options demonstrated improved cost-effectiveness if provided to bilateral compared with unilateral CMVR patients (irrespective of whether the patients received ART).
CRD COMMENTARY - Selection of comparators A justification was provided for the treatment strategies compared. They represented available administration options in the authors' setting, but robust data concerning their relative merits were not available. Ganciclovir was selected as the treatment medication on the basis that it represented the most commonly used medication in the authors' settings. However, alternative pharmaceutical treatments are available, but were not discussed in the current paper. You should decide if these represent valid comparators in your own setting. Validity of estimate of measure of effectiveness The parameters were derived from the published literature. The authors reported that a systematic review of the literature was undertaken. However, inclusion criteria relating to study designs and further details of the review were not reported, making it difficult to assess the validity of the estimates used. It was reported that the probability of contralateral CMVR was based on a meta-analysis conducted by the authors using a Bayesian fixed-effect approach. However, as the authors pointed out, one limitation to the study was that most estimates were derived from studies conducted in different settings and on different patient populations. It was not clear whether the authors considered the impact of differences between the identified studies when estimating effectiveness. In addition, the authors did not adopt a weighting scheme to reflect differences in sample size. Validity of estimate of measure of benefit The measure of benefit used in the economic analysis was the QALYs. The utility weights were based on data from four published studies and were augmented by authors' assumptions and information on a cohort of 362 patients receiving IVT in the authors' setting (Chiangmai University Hospital). Details of the valuation method used were not reported. The benefits were appropriately discounted. Validity of estimate of costs Perspectives of society and the health care system were adopted in the economic analysis. It appears that, for both perspectives, all the relevant categories of costs have been included. Although the unit costs and their sources were reported, the detailed micro costing methodology might have precluded the possibility of detailing all the quantities of resources used. This will hinder the analysis being easily reworked for other settings. Discounting of the costs was not relevant as they were incurred for a maximum of 1 year. The authors evaluated uncertainty in the cost data jointly with the effectiveness data, using probabilistic sensitivity analysis, to produce cost-effectiveness acceptability curves. The probability distributions assigned were reported. Other issues Although methodological differences prevented direct comparisons of the results with those of previous studies, several estimates (e.g. survival duration and utility estimates) were compared with those of other studies. In general, the estimates appeared to be in agreement. The authors addressed the issue of generalisability of the results to other settings, drawing attention to the limitations of the data used in the model. The results of the study do not appear to have been presented selectively. The authors' conclusions would appear to be an adequate reflection of the scope of the analysis. Apart from the limitations of the study (discussed above), the authors also pointed out that travelling and sick-leave cost estimates were assumed to be equal for all treatment strategies. This assumption is likely to have resulted in an underestimation of the true costs. In addition, the utility values derived from the literature, referred to a cohort of elderly (median age 75 years) patients with subfoveal choroidal neovascularisation and not CMVR patients. Implications of the study IVT ganciclovir would appear to be the preferred option for the treatment of HIV/AIDS patients with bilateral or unilateral CMVR. Although the authors did not make recommendations for further research, their discussion highlighted areas where more research-based information is necessary.
Source of funding Supported by a grant from the National Health Security Office, Thailand.
Bibliographic details Teerawattananon K, Iewsakul S, Yenjitr C, Ausayakhun S, Yenjitr W, Mugford M, Teerawattananon Y. Economic evaluation of treatment administration strategies of ganciclovir for cytomegalovirus retinitis in HIV/AIDS patients in Thailand: a simulation study. PharmacoEconomics 2007; 25(5): 413-428 Other publications of related interest Because readers are likely to encounter and assess individual publications, NHS EED abstracts reflect the original publication as it is written, as a stand-alone paper. Where NHS EED abstractors are able to identify positively that a publication is significantly linked to or informed by other publications, these will be referenced in the text of the abstract and their bibliographic details recorded here for information.
Briggs AH. Handling uncertainty in cost-effectiveness models. Pharmacoeconomics 2000;17:479-500.
Indexing Status Subject indexing assigned by NLM MeSH AIDS-Related Opportunistic Infections /drug therapy /economics; Antiviral Agents /economics /therapeutic use; Computer Simulation; Cost-Benefit Analysis; Cytomegalovirus Retinitis /drug therapy /economics /etiology; Data Collection; Ganciclovir /economics /therapeutic use; HIV Infections /complications; Humans; Quality-Adjusted Life Years; Thailand; Treatment Outcome AccessionNumber 22007001204 Date bibliographic record published 29/02/2008 Date abstract record published 29/02/2008 |
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