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Recombinant or urinary follicle-stimulating hormone? A cost-effectiveness analysis derived by particularizing the number needed to treat from a published meta-analysis |
Ola B, Papaioannou S, Afnan M A, Hammadieh N, Gimba 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 Two treatment strategies for assisted conception were studied. The intervention treatment was superovulation with recombinant follicle-stimulating hormone (Gonal F, Serono Pharmaceuticals), while the control treatment was superovulation with the highly purified urinary form (Metrodin H, Serono Pharmaceuticals).
Economic study type Cost-effectiveness analysis.
Study population The study population comprised patients who had undergone in vitro fertilisation (IVF) and intracytoplasmic sperm injections (ICSI) in which uFSH was used for superovulation. Eight patients were excluded because they were older than 40 years, an age group excluded from the meta-analysis from which the authors derived the effectiveness results. In total, 145 IVF and 58 fresh ICSI cycles in which uFSH was used, were reviewed.
Setting The study setting was secondary care in an assisted conception unit. The economic study was carried out in Birmingham, UK.
Dates to which data relate The study reviewed patients between 1 January and 31 December 1999. The effectiveness data were derived from a meta-analysis (Daya and Gunby, see Other Publications of Related Interest). The price year was 1999.
Source of effectiveness data The effectiveness data were obtained from a meta-analysis (Daya and Gunby, see Other Publications of Related Interest), which compared rFSH with uFSH.
Outcomes assessed in the review The outcomes assessed in the meta-analysis of Daya and Gunby, were the control event rate, the experimental event rate, the absolute risk reduction and the odds ratio. The clinical pregnancy rates (PEER) for specified age groups were assessed from patients of the clinic. From these outcomes, the authors then derived the number-needed-to-treat (NNT; reciprocal of the absolute risk reduction) and the particularised NNT (pNNT; NNT multiplied by the control event rate, divided by the PEER).
Study designs and other criteria for inclusion in the review The authors did not list the particular study designs included in Daya and Gunby's meta-analysis. The authors only stated that the meta-analysis was a rigorously conducted study of homogenous trials. The meta-analysis excluded patients older than 40 years of age.
Sources searched to identify primary studies The authors did not state the sources searched by Daya and Gunby.
Criteria used to ensure the validity of primary studies The authors did not state the criteria that Daya and Gunby used to ensure the validity of the primary studies.
Methods used to judge relevance and validity, and for extracting data Number of primary studies included The authors only used Daya and Gunby's study, but did not state the number of studies included in this meta-analysis.
Methods of combining primary studies The overall results of Daya and Gumby's meta-analysis were pooled using a fixed-effects model.
Investigation of differences between primary studies Results of the review The results of the review were as follows:
the control event rate was 21.6%, while the experimental event rate was 29.8%;
the absolute risk reduction was 3.7% (95% confidence interval, CI: 0.5 - 6.9);
the odds ratio was 1.2 (95% CI: 1.02 - 1.42; p=0.3);
the PEER was 37.7% (95% CI: 24.8 - 52.1) for those aged 30 years or younger, 29.9% (95% CI: 20 - 41.6) for those aged 31 to 35, and 30.6% (95% CI: 19.6 - 43.7) for those aged 36 to 40.
The authors derived the NNT and pNNT from these results. The NNT was -27. The pNNT was -19 (95% CI: -13.5 - -28) for those aged 30 years or younger, -24 (95% CI: -17 - -35.2) for those aged 31 to 35, and -23 (95% CI: -16.1 - -36) for those aged 36 to 40.
Measure of benefits used in the economic analysis The health benefit measure used in the economic analysis was the clinical pregnancies gained.
Direct costs The resource quantities and the costs were reported separately. The direct costs to the hospital were included in the economic analysis. The fixed direct costs per fresh cycle were for baseline assessments, treatment and follow-up, and the cost per metered dose of 200 microg GnRH agonist, both for IVF using uFSH and rFSH. The variable costs per unit were the cost per IU of FSH superovulation and the cost per IU human chorionic gonadotropin (hCG) for ovulation induction, for IVF in both study groups. The luteal support costs were the cost per IU hCG and the cost per 400 mg of progesterone pessary. The fixed and luteal support costs were the direct costs of a typical IVF cycle at the Assisted Conception Unit, Birmingham Women's Hospital. The variable costs were derived from the British National Formulary (1999). The price year was 1999. Discounting was unnecessary since all the costs were incurred during 1 year.
Statistical analysis of costs The resource use quantities and costs were treated as point estimates (i.e. the data were deterministic). Thus, sensitivity analysis should have been employed to identify critical areas of uncertainty associated with the estimates.
Indirect Costs The indirect costs were not included.
Sensitivity analysis No sensitivity analysis was carried out.
Estimated benefits used in the economic analysis See the 'Effectiveness Results' section.
Cost results The cost difference per cycle if rFSH was used instead of uFSH was 271.15 for those aged 30 years or younger, 310.83 for those aged 31 to 35, and 372.59 for those aged 36 to 40.
Synthesis of costs and benefits The estimated benefits and costs were combined using the cost per extra clinical pregnancy gained. An incremental analysis was performed. The incremental cost-effectiveness was:
for the 30 years of younger age group, 5,070.51 (range: 3,660.53 - 7,619.32) per extra clinical pregnancy gained;
for the 31 - 35 age group, 7,335.39 (range: 5,284.11 - 10,941.22) per extra clinical pregnancy gained; and
for the 36 - 40 age group, 8,569.67 (range: 5,998.70 - 13,413.24) per extra clinical pregnancy gained.
Authors' conclusions The pooled results of meta-analyses can be particularised to specific patient groups, from which the cost-effectiveness can be reliably estimated. The study also demonstrated that the incremental cost-effectiveness increased directly with the age of the patient and inversely with the pregnancy rate.
CRD COMMENTARY - Selection of comparators No specific justification was given for the comparator used, but it would appear to represent current practice in the authors' setting. You should decide if the comparator represents current practice in your own setting.
Validity of estimate of measure of effectiveness The authors derived their estimates of effectiveness data from a published meta-analysis (Daya and Gunby) and data from the patients in their own clinic. Although the authors did not explain in detail how the study was conducted, the meta-analysis seems to have been conducted rigorously, using homogenous trials and a fixed-effects model to pool the results. The authors stated that one of the limitations of using this meta-analysis was that secondary outcomes (e.g. differences in dosages or cancellation due to poor responses) could not be calculated in their study, as the meta-analysis did not measure such outcomes. If these had been measured, the cost-utility would have been derivable.
Validity of estimate of measure of benefit The estimation of benefits was obtained directly from the meta-analysis. The choice of benefit was justified as the authors sought to calculate the incremental cost to gain an extra clinical pregnancy.
Validity of estimate of costs All the categories of cost relevant to the perspective adopted were included in the analysis. For each category of cost, all the relevant costs were included in the analysis. The costs and the quantities were reported separately, which will enhance the generalisability of the results. Estimates of resource use quantities were derived from the resource use of a typical IVF cycle at the authors' setting. No sensitivity analysis of the quantities was conducted, which may limit the interpretation of the study findings. Fixed and luteal support unit costs were derived from the authors' setting. No statistical analysis of the prices was performed. The variable unit costs were derived from published sources, but no sensitivity analysis of the prices was conducted. This may also limit the interpretation of the study findings, as the authors did not consider uncertainty in the parameters. The price year was reported.
Other issues The authors made appropriate comparisons of their findings with those from other studies. The fact that resource use and the unit costs were reported separately greatly increases the generalisability of the authors' results. The authors do not appear to have presented their results selectively. They did not report any further limitations.
Implications of the study The authors suggested that the cost estimates they calculated in their study would be a useful guide to private patients, as 70% of them pay for assisted reproductive treatment. The cost estimates would also be useful and valuable to general practitioners, primary care groups and local health authorities, which are saddled with health resource allocations.
Bibliographic details Ola B, Papaioannou S, Afnan M A, Hammadieh N, Gimba S. Recombinant or urinary follicle-stimulating hormone? A cost-effectiveness analysis derived by particularizing the number needed to treat from a published meta-analysis. Fertility and Sterility 2001; 75(6): 1106-1110 Other publications of related interest Daya S, Gunby J. Recombinant versus urinary FSH for ovarian stimulation in assisted reproduction. Human Reproduction 1999;14:2207-15.
Oto HJ, Mannaerts BM, Driessen SG, et al. A prospective, randomised, assessor blind and multicenter study comparing recombinant and urinary follicle stimulating hormones (Puregon versus Metrodin) in in-vitro fertilisation. Human Reproduction 1995;10:2534-40.
Indexing Status Subject indexing assigned by NLM MeSH Adult; Aging /physiology; Budgets; Cost-Benefit Analysis; Female; Fertilization in Vitro /economics; Follicle Stimulating Hormone /therapeutic use /urine; Health Care Costs; Humans; Male; Meta-Analysis as Topic; Pregnancy; Pregnancy Rate; Recombinant Proteins; Retrospective Studies; Sperm Injections, Intracytoplasmic /economics AccessionNumber 22001001196 Date bibliographic record published 30/04/2004 Date abstract record published 30/04/2004 |
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