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Valacyclovir prophylaxis for the prevention of Herpes simplex virus reactivation in recipients of progenitor cells transplantation |
Dignani M C, Mykietiuk A, Michelet M, Intile D, Mammana L, Desmery P, Milone G, Pavlovsky S |
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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 use of valacyclovir (VAL; Valtrex; GlaxoWellcome) compared with intravenous acyclovir (ACY; Filaxis) for the prevention of Herpes simplex virus (HSV) reactivation. VAL was administered orally at a dose of 500 mg twice daily, from day -3 of autologous progenitor cell transplantation (APCT) until recovery from neutropenia, day +30, severe toxicity, or HSV reactivation, which ever came first. Intravenous ACY was administered at a dose of 5 mg/kg twice daily, from day -3 until recovery from neutropenia.
Economic study type Cost-effectiveness analysis.
Study population The study population comprised HSV seropositive APCT patients.
Setting The setting was secondary care. It was unclear whether the study was conducted in the USA or Argentina.
Dates to which data relate The effectiveness evidence was collected between January 1996 and April 1999. The dates when the costs were collected were not reported. A price year was not given.
Source of effectiveness data The effectiveness data were derived from a single study.
Link between effectiveness and cost data The costing was carried out retrospectively on the same patient sample as that used in the effectiveness study.
Study sample The study sample comprised all APCT patients older than 12 years who tested positive for HSV immunoglobulin G antibodies by indirect immunofluorescence during the study period. This sample was appropriate for the clinical question since it included patients at risk from HSV reactivation. Power calculations, to estimate the impact of chance on the results, were not reported to have been carried out. There were 108 patients in the VAL group, 43 in the ACY group and 38 in the no HSV prophylaxis group. The patients in the VAL group had a median age of 45 years (range: 13 - 65) and 59 were male. In the ACY group, the median age was 43 years (range: 2 - 64) and 23 patients were male). In the no HSV prophylaxis group, the median age was 39 years (range: 7 - 66) and 19 were male. It was not reported whether any patients refused to participate or were excluded for any reason.
Study design This was a comparative study with historical controls that seems to have been conducted at a single centre. The patients were followed from day-3 of ACPT until a maximum of 30 days post APCT. No loss to follow-up was reported.
Analysis of effectiveness The analysis appeared to have been conducted on an intention to treat basis, although this was not explicitly stated. The primary health outcome was HSV reactivations (and the associated site), although the number of viral cultures taken was also noted. The authors also noted the median duration of VAL prophylaxis and reasons for discontinuation. The authors compared the groups in terms of diagnosis and median duration of neutropenia. They did not draw the readers' attention to any clinically important differences.
Effectiveness results There were three (2.7%) HSV reactivations in the VAL group (all genital), one (2%) in the ACY group (oral), and 17 (45%) in the no treatment group (14 oral, 2 genital and 1 both sites).
Forty-four (40%) viral cultures were taken in the VAL group, 5 (12%) in the ACY group, and 23 (60%) in the no treatment group.
The median duration of VAL prophylaxis was 14 days (range: 1 - 26).
Reasons for discontinuation of VAL were end of prophylaxis (84 patients, 78%), oral intolerance (17 patients, 15%), suspected HSV reactivation (5 patients, 5%), toxicity (1 patient, 1%), and other (1 patients, 1%).
Clinical conclusions The authors concluded that VAL was well tolerated and was as effective as intravenous ACY.
Measure of benefits used in the economic analysis The authors did not estimate a summary measure of benefit. In effect, a cost-consequences analysis was conducted.
Direct costs The authors were concerned only with the cost of the actual treatments, that is, a day of intravenous ACY prophylaxis at the given dose and the cost of viral cultures. These estimates seem to have been based on the costs at the study setting, although this was not stated explicitly. The cost estimates do not appear to have included any overheads or staff-related costs. Discounting was not required, owing to the short time horizon during which the patients were treated. The unit costs were not reported separately from the quantities, although the number of days of treatment was reported separately. The exact dates when the unit costs and quantities were collected were not reported, although the authors did state that the costing was carried out retrospectively.
Statistical analysis of costs The costs were treated deterministically.
Indirect Costs The indirect costs to the patients or society were not estimated, despite being potentially relevant on account of the age of the patients involved and the possibility of lost earnings due to treatment.
Sensitivity analysis The authors did not report whether sensitivity analyses were carried out.
Estimated benefits used in the economic analysis See the 'Effectiveness Results' section.
Cost results VAL cost $200 per patient, ACY cost $1,210 per patient, and no HSV prophylaxis cost $409 per patient.
Synthesis of costs and benefits Authors' conclusions Valacyclovir (VAL) can be considered a safe and less expensive alternative to intravenous acyclovir (ACY) for the prophylaxis of Herpex simplex virus (HSV) in autologous progenitor cells transplantation (APCT) patients.
CRD COMMENTARY - Selection of comparators The authors compared VAL with intravenous ACY in preventing HSV reactivation. There was a full discussion of the available prophylaxis and a comparison of existing cost and effectiveness evidence. Intravenous ACY appears to have been current practice in the authors' setting. You should decide if this represents a valid comparator in your own setting.
Validity of estimate of measure of effectiveness The analysis was based on a comparative study with historical controls. This enabled a comparison of the treatments in a true to life setting, but meant that there was no control of potentially confounding variables. The authors stated, "all the groups had the same risk of developing the study endpoint". However, in defining the no prophylaxis group they also reported that these patients did not receive prophylaxis because "they were expected to develop less severe mucositis". This factor introduced a systematic difference between the groups, suggesting a source of bias. The study sample was representative of the study population since it included patients at risk from HSV reactivation. The study might have been improved by a statistical analysis to test for significant differences between the groups, and sensitivity analyses to assess whether the results might be transferable to other settings. Given the nature of the study design, the internal validity is likely to be low.
Validity of estimate of measure of benefit The authors did not derive a summary measure of health benefit. Therefore the analysis was categorised as a cost-consequence study.
Validity of estimate of costs Very few details of the cost analysis were reported. The authors suggested that the costing was carried out retrospectively and the study was not designed to be a cost-effectiveness analysis. The perspective of the study was not reported, making it difficult to assess the quality of the costing. However, the inclusion of only two sources of costs (prophylaxis and culture) suggests that a number of important cost sources were omitted, irrespective of the perspective taken. From a provider perspective, for instance, overheads and staff costs should have been included. These problems suggest that the costs reported should be considered as no more than an indicative source of information, and that until further evidence on the cost is available, these results should not be used to inform clinical decision-making.
Other issues The authors made some limited comparisons of their findings with those from other authors, particularly results pertaining to oral ACY. However, as the authors did not report results for oral ACY, this comparison is not clear. The authors considered the issue of generalisability by suggesting that VAL savings might be higher in settings with a greater incidence of HSV reactivation. Broader issues of generalisability that might have been addressed through sensitivity analyses were not discussed. The conclusions were an accurate reflection of the scope of the analysis, in relation to the study population, and were indicative of the results presented.
Implications of the study The authors did not make any recommendations for policy or practice, although they suggested that their findings should be confirmed in a "prospective trial directed towards assessing efficacy, safety, and appropriate dosing".
Source of funding Partly financed by an educational grant from GlaxoSmithKline, Argentina.
Bibliographic details Dignani M C, Mykietiuk A, Michelet M, Intile D, Mammana L, Desmery P, Milone G, Pavlovsky S. Valacyclovir prophylaxis for the prevention of Herpes simplex virus reactivation in recipients of progenitor cells transplantation. Bone Marrow Transplantation 2002; 29(3): 263-267 Indexing Status Subject indexing assigned by NLM MeSH Acyclovir /administration & Adolescent; Adult; Aged; Antiviral Agents /administration & Costs and Cost Analysis; Female; Hematopoietic Stem Cell Transplantation /adverse effects /methods; Herpes Simplex /drug therapy /prevention & Humans; Male; Middle Aged; Simplexvirus /drug effects /growth & Transplantation, Autologous /adverse effects /methods; Treatment Outcome; Valine /administration & Virus Activation /drug effects; control; derivatives /economics /standards; derivatives /economics /standards; development; dosage /analogs & dosage /analogs & dosage /economics /standards AccessionNumber 22002006548 Date bibliographic record published 28/02/2005 Date abstract record published 28/02/2005 |
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