Center of Pharmacoeconomics, Institute of Pharmacological Sciences, University of Milan, Via Balzaretti 9, I-20133, Milan
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Abstract |
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Key words: costs/cost-effectiveness analysis/in-vitro fertilization/Italy/recombinant FSH
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Introduction |
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Materials and methods |
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Efficacy data
It has been shown that r-FSH has improved efficacy/effectiveness as compared with u-FSH preparations, e.g. more pregnancies and a shorter treatment period with a lower total dose of FSH (Out et al., 1995). The results of a recent meta-analysis of three prospective, multicentre, randomized and comparative trials confirm the superiority of r-FSH versus u-FSH (Out et al., 1997
). A 5% statistically significant difference was found in the ongoing pregnancy rate at 12 weeks and a 6.4% difference when the cryoprogram was included.
Cost data
Because of the fact that infertility is usually not considered as a disease, according to the classic World Health Organization definition, the current reimbursement practice of IVF procedures in Italy is rather complex. No national health service (NHS) tariff exists for IVF treatment in Italy, although there are proposals made by the Italian Ministry of Health. Therefore, private tariffs have been used as a proxy for the costing of IVF treatment, since 7090% of the IVF cycles are performed in the private setting. Hence, no average public data on tariffs for the various regions are available. The NHS perspective was only considered for drugs because these are reimbursed by the NHS. With regard to the reimbursement of recombinant FSH it has been assumed that r-FSH (Puregon®) is reimbursed at the same level as u-FSH (Metrodin HP®). Table I gives an overview of the costs per cycle of the private tariffs used in the model. The costs of urinary FSH and recombinant FSH were based on the average number of international units (IU) used in the study of Out et al. (1996). These were 2385 IU of urinary and 2137.5 IU of recombinant FSH. Since urinary FSH is no longer available on the Italian market, the cost of highly purified urinary FSH was incorporated into the model. Although it is likely that urinary FSH and highly purified urinary FSH differ in safety, it cannot be assumed that they are different in efficacy, which is the focus, together with costs, of this analysis (leCotonnec et al., 1993
; Hugues, 1994
; Lambert et al., 1995
). Since national tariff codes and real cost data for IVF procedures are not widely available, and differ from region to region, it was necessary to use the private tariffs as a proxy for the public setting. In addition, for the public setting the cost overview from one of the centres was also considered, because it allowed us to employ this in each individual step of the IVF procedure.
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Results |
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Cost-effectiveness
An incremental cost effectiveness ratio was estimated for the private sector, the public sector, and also for the current situation (Table IV). These were based on the simulation on a time horizon of 1 year of treatment with r-FSH versus u-FSH of a cohort of 10 000 patients undergoing IVF in Italy. This number corresponds, based on the answer of the panel, to the estimated number of women who undergo IVF yearly in Italy. The analysis was limited to the third cycle. The cumulative pregnancy rates, including thawed embryos, on the basis of the model was 62.2% for r-FSH and 49.66% for u-FSH over three cycles, thus leading to an excess of 1255 (6221 versus 4966) pregnancies in the cohort treated with r-FSH. There would be a global 22 457 started IVF cycles in the r-FSH cohort and 24 323 in the u-FSH group. The difference is attributable to the higher pregnancy rate of r-FSH compared to u-FSH, which would limit the number of second and third cycles started in the r-FSH cohort. According to this model the total cost of r-FSH and u-FSH would be 72 and 36.5 billion Lire respectively.
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Results for the cases in which all the IVF treatments were performed either in the public sector or in the private sector are similarly presented in Table IV.
Sensitivity analysis
To test the robustness of the calculations, a univariate sensitivity analysis was conducted on the most relevant parameters (public sector, NHS perspective). The parameters were therefore varied by ± 20%, e.g. the pregnancy rate (including thawed embryos) of Puregon® (27.7%) was used and multiplied either by 1.2 (= 33.24%) or by 0.8 (= 21.76%). Results are presented in Figure 2a,b together with the two-way sensitivity analysis on both effectiveness and cost on Puregon® (simultaneous 20% increase in effectiveness and decrease in cost; simultaneous 20% decrease in effectiveness and increase in cost). The incremental cost effectiveness ratios were highly sensitive to changes in cost and efficacy/effectiveness of Puregon®.
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Discussion |
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Regarding social aspects, there appears to be evidence of value placed in going through IVF, even if the couple remains childless (Ryan, 1996). Unfortunately, only a few such studies have been performed to date and some have given large ranges, depending on how the questions were framed (Neumann and Johannesson, 1994
; Ryan, 1996
). Results of the present study are in line with the more recent analyses of cost and effects of IVF treatments, although such analyses have been conducted in different countries, with different health-care systems (Collins et al., 1997
; Fattore and Lazzaro, 1998
; Wølner-Hanssen and Rydhstroem, 1998
). Previous economic analyses have not addressed the economic benefit of r-FSH versus u-FSH, but rather the overall cost-effectiveness of the IVF procedure itself. The present analysis is, to the best of our knowledge, the first cost-effectiveness analysis of recombinant versus u-FSH in Italy. In spite of significantly higher acquisition costs, r-FSH compares favourably to u-FSH in the present study. It goes without saying that the value of a technology has not only to be assessed on the basis of its price but on its overall impact, in order to avoid misleading conclusions.
The total estimated cost to society according to the current situation would amount to approximately 197.1 and to 171.6 billion Lire (116.6 and 101.5 million $US) per year in the r-FSH and in the u-FSH cohort respectively. In addition, the cost of days lost from work and patients' travel expenses would have to be added to this figure, to capture the overall societal costs. These costs have not been included in the analysis because of the large variability of employment status among women from different centres and because of the large proportion of women referring to centres but coming from other (even very distant) areas characterized by different employment rates. It is reasonable that given the higher efficacy of r-FSH, women would undergo fewer treatments compared to u-FSH, thus leading to a more favourable cost effectiveness ratio for Puregon®. Unfortunately IVF techniques have been excluded from many health-care provision systems, e.g. third party payers, governments and health plans, as infertility is often viewed as a social condition, not a medical condition, and coverage for infertility diagnosis and treatment is often viewed as unnecessary in the bundle of health-care services provided.
It should be pointed out that in general, recombinant technologies have additional advantages, e.g. the possibility of achieving a theoretically unconstrained supply of the active principle, whereas urine-derived technologies have limitations on the availability of raw materials. This study suffers from potential limitations, related to the fact that this analysis is based on an adaptation to Italy of a meta-analysis of clinical trials and of a clinical trial itself. Any statement on how good an adaptation this is must eventually rely on a judgement of the representativeness of experts; about this, it should be acknowledged that every possible effort has been made to choose representative experts and to get valid answers (e.g. consistency of experts' answers with market data where sought and found). Ideally, future research should favour prospective economic assessments of IVF strategies. This is the first study to investigate IVF in Italy systematically with the tools of medical technology assessment and to draw a picture of the current, indeed confused, reimbursement situation.
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Conclusions |
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Acknowledgments |
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Notes |
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References |
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Submitted on July 25, 1998; accepted on December 10, 1998.