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Cost-effectiveness of primary offer of IVF vs. primary offer of IUI followed by IVF (for IUI failures) in couples with unexplained or mild male factor subfertility |
Pashayan N, Lyratzopoulos G, Mathur R |
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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 examined a primary offer of in vitro fertilisation (IVF), instead of offering intrauterine insemination (IUI) first.
Economic study type Cost-effectiveness analysis.
Study population The study population comprised couples with unexplained or mild male factor subfertility who were eligible for both IUI and IVF treatment strategies.
Setting The setting was secondary care. The economic study was carried out in the UK.
Dates to which data relate The effectiveness evidence was drawn from a UK register held between 1995 and 1999 and from studies published between 1997 and 2005. The costs were drawn from a document published in 2004. No price year was stated.
Source of effectiveness data The effectiveness data were derived from a review or synthesis of published studies and estimates of effectiveness based on local activity data.
Modelling A mathematical model was used to establish the cost-effectiveness of different treatment strategies, including transitions from one treatment stage or strategy to another. For each IUI modality, the activities and outcomes were estimated for up to 6 cycles of treatment.
Outcomes assessed in the review The outcome assessed from the literature was the live birth rate (LBR) following a treatment cycle.
Study designs and other criteria for inclusion in the review The authors searched for new studies on the LBR of the IUI modalities and IVF.
Sources searched to identify primary studies The authors stated that the basis for the effectiveness evidence was the UK National Institute for Clinical Excellence (NICE) Guidance on subfertility treatments. They also searched MEDLINE.
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 Three primary studies were included in the review. However, the results from only one study were directly incorporated. This was the UK's Human Fertilisation and Embryology Authority (HFEA) population-based register 1995 - 1999, as used in the NICE Guidance. Data from a local unit covering the period 1993 to 2003 were also included.
Methods of combining primary studies The outcomes from the studies were not combined.
Investigation of differences between primary studies Results of the review It was assumed that the IVF effectiveness data were applicable for couples receiving IVF following failure of IUI.
The LBR following a U-IUI cycle was 3.5%, a judgement based on halving local activity data on GS-IUI in line with the literature.
The LBR following a CS-IUI cycle was 3%, a judgement based on local activity data on GS-IUI and the literature.
Ten per cent of couples failing IUI treatment would drop out of subfertility treatment. The LBR following a "full" IVF cycle was 19.26% (all ages) whilst that following a "frozen" IVF cycle was 10.40% (all ages), based on the HFEA.
The average LBR following a GS-IUI cycle was 7%, based on local activity data.
In a further scenario, LBR values of 10% for the 1st cycle, 6% for the 2nd cycle, 4% for the 3rd cycle, 4% for the 4th cycle, 2% for the 5th cycle and 2% for the 6th cycle were obtained.
Methods used to derive estimates of effectiveness Informed judgement was used to derive the following estimates.
Estimates of effectiveness and key assumptions There was a 1:1 ratio between fresh and frozen cycles, assuming 25% of couples have 0 frozen embryo transfer (FET), 50% have 1 FET and 25% have 2 FET.
The ratio between IVF and IVF/intracytoplasmic sperm injection was 1:1.
There was 100% compliance and 0% dropout with IUI treatment.
Measure of benefits used in the economic analysis The outcome measure used in the economic analysis was the number of live birth-producing pregnancies.
Direct costs Discounting was not reported but it might not have been necessary as the time required to complete 6 cycles was not stated. The costs and the quantities were not reported separately, although the costs per cycle of treatment were referenced to the NICE Guidance on subfertility treatments published in 2004 (see 'Other Publications of Related Interest' below for bibliographic details) where more detail may be available. No price year was stated. The costs were related to resources directly associated with fertility treatment and excluded those arising from potential complications and/or multiple pregnancies. It was not stated whether the NICE estimate of costs per cycle had been derived from primary or secondary data, or whether it had been modelled. However, the cost per cycle of CS-IUI was simply assumed to be halfway between the costs of U-IUI and GS-IUI. The total cost to the health service was taken as the sum of the costs of IUI and IVF activity generated by each scenario.
Statistical analysis of costs The costs were treated deterministically.
Indirect Costs No indirect costs were considered.
Sensitivity analysis Univariate sensitivity analysis was carried out, using alternative LBR values for U-IUI, GS-IUI and CS-IUI. Ranges were derived from different value estimates in the literature or, in the absence of literature, from local experience, expert opinion or assumptions.
Estimated benefits used in the economic analysis The results were presented as strategies of primary IVF compared with primary IUI (from 1 to 6 cycles) plus IVF. The results for three different IUIs (unstimulated, gonadotrophin and clomifene) were presented. The strategy of primary IVF was associated with 26 live births. Compared with primary IVF:
incremental live births associated with U-IUI before IVF varied from 0 (1 cycle) to 12 (6 cycles);
incremental live births associated with GS-IUI before IVF varied from 2 (1 cycle) to 24 (6 cycles); and
incremental live births associated with CS-IUI before IVF varied from -1 (1 cycle) to 11 (6 cycles).
The side effects of treatment were not considered in the economic analysis.
Cost results The total cost of a primary offer of IVF was 321,700 per 100 couples.
The total cost of a primary offer of U-IUI plus IVF varied from 324,300 per 100 couples (1 cycle) to 495,900 per 100 couples (6 cycles).
The total cost of a primary offer of GS-IUI plus IVF varied from 369,800 per 100 couples (1 cycle) to 759,800 per 100 couples (6 cycles).
The total cost of a primary offer of CS-IUI plus IVF varied from 356,000 per 100 couples (1 cycle) to 678,900 per 100 couples (6 cycles).
The costs of adverse effects or knock-on costs were not dealt with in the costing.
The incremental costs associated with offering U-IUI ranged from 2,600 (1 cycle) to 174,200 (6 cycles). Those associated with offering GS-IUI ranged from 48,100 (1 cycle) to 438,100 (6 cycles) and those associated with CS-IUI from 34,300 (1 cycle) to 357,200 (6 cycles).
Synthesis of costs and benefits The estimated benefits and costs were combined in incremental cost-effectiveness ratios (ICERs).
Compared with a primary offer of IVF, the ICER for offer of 1 to 6 cycles of U-IUI followed by IVF decreased from 18,600 to 14,200 per additional live birth, respectively.
The ICER for offer of 1 to 6 cycles of GS-IUI followed by IVF decreased from 24,000 to 18,300 per additional live birth, respectively.
The ICER for offer of 2 to 6 cycles of CS-IUI followed by IVF decreased from 49,400 to 32,500 per additional live birth, respectively.
One cycle of CS-IUI before IVF was dominated by a primary offer of IVF.
After considering different plausible LBR values for IUI modalities, the authors concluded that a primary offer of IVF remained "more" cost-effective.
In sensitivity analysis, the cost per additional live birth ranged from a minimum of 7,500 to 91,700 (both associated with 2 cycles of U-IUI before IVF, depending on LBR rate).
Authors' conclusions A primary treatment offer of any modality of intrauterine insemination (IUI), instead of a primary offer of in vitro fertilisation (IVF), is cost-ineffective and is associated with high opportunity costs.
CRD COMMENTARY - Selection of comparators No justification was given for the comparators chosen, but reference was made to recent NICE Guidance. You should decide whether they are appropriate comparators in your own setting.
Validity of estimate of measure of effectiveness The authors based their analysis primarily on a systematic review carried out by NICE. A further review of the literature was undertaken but, since the methods were not reported, it was unclear whether the review was conducted in a systematic way in order to identify relevant research and minimise bias. The authors used data from the available studies selectively and did not consider the impact of differences between the primary studies when estimating effectiveness. Many inputs were estimated by combining informed opinion and literature estimates. These estimates were investigated in a sensitivity analysis. The ranges used appear to have been appropriate, but the wide variance in the ICER results indicated the relatively high influence of these uncertain inputs.
Validity of estimate of measure of benefit The estimation of benefit (live births) was derived from the effectiveness analysis using a mathematical model.
Validity of estimate of costs Although the authors reported that a health service perspective was adopted, the costs of monitoring and follow-up, side effects, complications and/or multiple births were omitted from the analysis, on the grounds that they were similar across treatments. If that is true, these omissions should not affect the conclusions drawn. The costs and quantities were referenced to the NICE Guidance publication and were not reported separately, making transferability of the study difficult. The price year was not reported and no sensitivity analysis of the costs was performed.
Other issues The authors made appropriate comparisons with the results of other studies which they found, in general, did not investigate the use of IVF in couples failing IUI treatment. The authors addressed the issue of generalisability, stating that the local activity data used in the model should be a better reflection of the current UK situation and, therefore, more desirable than generalising published data to the UK setting. The authors did not present their results selectively.
The authors acknowledged a number of limitations. First, a prospective randomised controlled trial would have been a superior study design to answer the study question. Second, published data comparing IVF and IUI are scarce and variable. Third, IUI effectiveness in the literature may be overestimated because data have generally been derived from uncontrolled retrospective case series and cohort studies, and are not well reported. Finally, the outcome employed did not account for patients' philosophical preferences. The authors also noted that average rather than age- or indication-specific LBRs were used, but they believed that, as with the cost omissions, this would not affect the conclusions reached.
Implications of the study The authors stated that the additional and avoidable costs (associated with IUI) put pressure on the health care system to cope with extra demand and activity for a treatment of low effectiveness, making the wider availability of the most effective treatment (IVF) more difficult, and thus disadvantaging couples who could otherwise have benefited from it.
Bibliographic details Pashayan N, Lyratzopoulos G, Mathur R. Cost-effectiveness of primary offer of IVF vs. primary offer of IUI followed by IVF (for IUI failures) in couples with unexplained or mild male factor subfertility. BMC Health Services Research 2006; 6(80) 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.
National Collaborating Centre for Women's Children's Health. Fertility: assessment and treatment for people with fertility problems. Clinical Guideline. London: RCOG Press; 2004.
Indexing Status Subject indexing assigned by NLM MeSH Cost-Benefit Analysis; Decision Support Techniques; Embryo Transfer /economics /utilization; Female; Fertilization in Vitro /economics /utilization; Gonadotropins /therapeutic use; Health Care Costs; Humans; Infertility, Male /drug therapy /economics; Insemination, Artificial /economics /utilization; Live Birth /economics; Male; Models, Statistical; Pregnancy; Treatment Outcome AccessionNumber 22006001881 Date bibliographic record published 28/02/2007 Date abstract record published 28/02/2007 |
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