The cultural and emotional importance of having and raising healthy children is undisputed. Cross-cultural solutions to problems resulting from involuntary childlessness have included such strategies as adoption, finding new partners, and dissolving marriages that do not produce offspring. While both males and female infertility may result from heritable factors, environmental exposures, and disease, it is usually the result of functional incapacity in youth and in old age. The high value attached to reproduction is not puzzling. Human reproduction is protected by strong basic instincts. Childlessness is seldom met with stoicism by those who wish to have children. The happiness that follows the successful birth of a wanted child must not be discounted. Traditional definitions of “family” imply “offspring” before the acknowledgment of other memberships.

The Human Fertilisation and Embryology Act of the United Kingdom was passed in 1990, leading to the formation of the Human Fertilisation and Embryology Authority (HFEA), the first statutory body to regulate and control assisted conception anywhere in the world. The principal function of the HFEA is to license and monitor clinics that carry out in vitro fertilization (IVF), donor insemination (DI), and embryo research. Information on over 135,000 treatment cycles, 20,000 pregnancies, and 25,000 babies following IVF has now been collected as part of the regulatory process, and these data have permitted unbiased and accurate evaluation of treatment efficacy using pregnancy and live-birth rates. The treating clinics are required by law to provide information on the outcome of all births, including neonatal mortality and congenital malformations, but there is no systematic validation of these data using medical records or any follow-up of treated women, or babies, over time. In addition, the strict confidentiality of data supplied to the HFEA means that outside researchers have been unable to access the database for research projects. Thus, at the present time, it is not possible to evaluate the long-term safety of assisted conception procedures using HFEA data. There is reasonable scientific evidence to justify full investigation of the health of both treated women and resulting children. Particular health outcomes requiring evaluation include obstetric complications, preterm births, cerebral palsy, and cancer. The HFEA has recognized the need for follow-up studies and is currently investigating ways of enabling research projects using HFEA data to be undertaken.

The Centers for Disease Control and Prevention published the first Assisted Reproductive Technology (ART) Pregnancy Success Rate Report in 1997. This article presents a description of the law that initiated the public report, a description of the surveillance system used to accumulate data for the report, and some of the results from ART cycles intitiated in 1995.

The process of technology assessment is evolving. The process of policy development for technology is the least understood in the cycle of technology assessment. The process of policy development, which should involve extensive consultation and a broad-based research and evaluation program, is often fraught with difficulties and can cause further analysis or the assessment process to come grinding to a halt. This article reviews some social, political, and ethical issues and the role of civil society in influencing the technology assessment process for new reproductive technologies in Canada. It is written from the perspective of one of the Deputy Directors of Research and Evaluation for the Royal Commission on New Reproductive Technologies and highlights the strengths and difficulties of technology assessment when civil society and technology assessment come face to face. A brief update by a policy analyst in Health Canada on the current situation of legislation on new reproductive technologies has been provided and is included at the end of this article.

In vitro fertilization (IVF) stands out as one of the contemporary period's most extraordinary technologies, and its social and ethical consequences among the most far reaching. Despite its uncertain effectiveness and medical consequences, IVF has contributed significantly to the medicalization of infertility and the increasingly imperative character of reproductive technology. New developments in IVF, particularly oocyte donation, have created new definitions of treatable infertility and new social needs for IVF; when the technology does not result in pregnancy or healthy babies, these developments have created profound new disappointments. IVF and the commodification of the extracorporeal embryo have also confused the social meaning and legal definition of parenthood. Ultimately the relationship between prospective parents, infertility specialists, and the embryos that they create is a highly ambiguous one. This ambiguity is likely to be a long-term characteristic of efforts to develop, use, and assess assisted reproductive technologies.

The long-term health sequelae for women from assisted reproductive technology (ART) have not been studied extensively. There are a number of reasons that women's health may be compromised after ART procedures, including the consequences of the increased incidence of multiple births, operative deliveries, and preterm infants, the possible adverse effects of the drug regimens used for ovarian stimulation, and the instrumentation involved in ART procedures. In this paper we review the existing literature in these areas. It emphasizes the effects of the drugs used for ovarian stimulation, and in particular the incidence of cancer among women who have undergone ART. The review indicates that there is cause for concern about the long-term effects on women from ART treatments. It highlights the lack of research undertaken in almost all areas related to women's long-term health after ART. In the area of ART and cancer, it draws attention to the lack of conclusive evidence in relation to the posited association between fertility treatments and cancer, resulting from the limited number of very large studies and the need for longer follow-up periods. We make a number of recommendations regarding further research that is needed to address the current shortcomings in the published literature.

This paper provides an overview of the effects of in vitro fertilization (IVF) on the children born from it. One of the main problems with IVF to date remains the high incidence of multiple pregnancies, which carry an inherent higher risk of preterm delivery and, therefore, of increased morbidity and mortality in newborns. Further, singleton pregnancies and twin pregnancies from IVF compared to control singleton or twin pregnancies appear to be at higher risk of preterm birth and low birth weight. Whether this is an effect of the procedure per se or is related to maternal factors, or a combination of both, remains to be studied. The risk of congenital malformations does not, with the available data, seem to be elevated. As of now, it remains unclear whether embryo freezing is a safe procedure. Psychomotor development of children born through IVF does not seem to be disturbed. Until further and more extensive studies are conducted, it remains unclear whether IVF poses long-term risks for the children.

This paper examines the current status of in vitro fertilization and embryo transfer (IVF-ET) as a treatment for various types of infertility. We reviewed studies on the efficacy and safety of IVF-ET and intracytoplasmic sperm injection (ICSI) plus IVF-ET, compared with conventional treatment or no treatment for various infertility diagnoses. Material retrieved included English language publications between 1992 and January 1997 that reported the results of prospective controlled clinical trials, cohort studies, and retrospective comparative studies with large series, and reviews presenting risks, complications, and longer-term health consequences associated with IVF-ET and ICSI. No adequate prospective comparative studies of sufficient power on the use of IVF-ET for specific infertility diagnoses have been reported to date. Most of the published reports concerning results with IVF-ET as a treatment of infertility have been based upon small, uncontrolled studies, with various methodological weaknesses. Reported results are not directly comparable. There are few follow-up data on outcomes after pregnancy is established or on long-term health consequences of the use of IVF-ET on mothers and their babies. IVF-ET has diffused widely without comprehensive assessment of its efficacy and safety. The available evidence supports its use only for severe bilateral tubal occlusion. For other diagnoses of infertility the evidence is limited and does not establish whether IVF-ET is effective. Long-term, well-designed, prospective clinical trials are required to determine when and for what indications IVF-ET is effective and what its health effects are on both mothers and their babies.

This paper examines the extent to which it is possible to measure the social importance, or macro benefits, of health care. In contrast to the many micro studies of the benefits of specific health care interventions, methodology relating to such macro benefits is at a very rudimentary stage. A theoretical model is presented that seeks to capture the social consequences of a health care system. In light of this model, three existing empirical approaches to answering the question are examined: the inventory approach, the avoidable mortality approach, and the production function approach. All three have severe limitations in terms of the underlying theoretical model, data availability, and analytic tools employed. A more fruitful approach may be to investigate the value of undertaking a direct survey of citizens' attitudes toward their health care system.

Multiple myeloma is a disorder of the bone marrow that is associated with bone pain and osteolytic lesions. These complications can lead to the development of pathologic fractures and severe patient morbidity. However, the results of a recent randomized trial in patients with multiple myeloma demonstrated that single 90 mg monthly doses of pamidronate as an adjunct to chemotherapy reduced the incidence of skeletal-related events and improved patients' quality of life. A cost-benefit analysis using an ex-ante insurance willingness-to-pay (WTP) approach was conducted from a Canadian societal perspective to estimate the net cost or benefit of prophylactic pamidronate therapy for patients with multiple myeloma. This included direct costs for drug administration and hospital savings secondary to avoiding skeletal-related events. One hundred Canadian taxpayers were then interviewed to ascertain their maximum WTP for the benefits of pamidronate. The WTP survey instrument was simple to administer and easily understood by participants. Respondents stated that they would be willing to pay an average of Can $3,364 (95% CI: $2,096, $4,632) as an income tax increase to be paid over their lifetime for the value offered by the product. The benefit was then subtracted from the overall cost of nine monthly doses of pamidronate ($4,153) producing a net societal cost of $789 per patient (95% CI: (−$479, $2,057). The administration of monthly pamidronate therapy in multiple myeloma patients produces a situation of cost neutrality (societal benefits = costs). Additional clinical trials to identify high-risk patient subgroups that would most benefit from the drug are needed.

This paper tests the null hypothesis of a zero effect of cesarean section rate on health outcome against the alternative of a positive effect. Using data from 59 hospitals in Sweden from 1988–92, we specify two separate linear regression models for health outcome, one with perinatal mortality, and the other with rate of asphyxia, as dependent variable. We estimate the models by single-year cross-section regressions and as pooled data systems. The null hypothesis cannot be rejected, i.e., we do not find any significant positive effect of cesarean section rate on health outcome. Thus, we conclude that an increase in cesarean section rate does not imply lower perinatal mortality or lower rate of asphyxia. This in turn indicates that the minimum cesarean section rate is optimal.

We conducted a retrospective cohort study based on a case note review to determine whether there are differences in the treatment pathways followed for men and women admitted with acute myocardial ischemia and infarction after adjusting for differences in case mix. Women were as likely as men to receive thrombolysis, but were less likely subsequently to undergo exercise testing (adjusted odds ratio, 0.58; 95% CI, 0.40–0.84) or angiography (adjusted odds ratio, 0.62; 95% CI, 0.39–0.99). Coronary anatomy was the strongest predictor of revascularization regardless of sex. Women with diagnosed cardiac pain are less likely than men to be placed on the investigative pathways that lead to revascularization. Those women who are investigated are as likely as men to undergo revascularization. These findings are independent of the effects of age, angina grade, comorbidity, or cardiac risk factors. Clinicians' and patients' beliefs and preferences about treatment require investigation.

This article dicusses the individual's choice to engage in informal care as an issue for economic evaluation. Traditional methods used in economic evaluation studies for valuing time spent on informal care are discussed and an alternative method is put forward that incorporates the quality of life of caregivers as an outcome measure to represent the effects on caregivers. The methodological issues concerning the valuation of informal caregivers' time are becoming more important as new drugs and other health care technologies are introduced for patients with diseases that are typically associated with informal care.

Using the example of substitution of peripheral blood stem cell (PBSC) collection to bone marrow harvest for autologous transplantation in cancer patients, our study attempts to illustrate how economic assessment, starting at an early stage of medical innovation, can influence the development and diffusion process of a new technological procedure whose optimal design has not yet been established. Two cost minimization studies comparing costs for obtaining a clinically reinfusable graft using bone marrow harvest or alternatively various protocols of PBSC collection contributed to a change in the French clinical standard for this procedure.

The differential staining cytotoxicity (DiSC) assay involves in vitro drug panel testing against patient tumor cells to identify optimal therapy. This observational study investigated whether DiSC assay guided treatment could improve outcome in patients with chronic lymphocytic leukemia. A cohort of 178 patients were categorized either as sensitive to drugs in vitro and receiving a sensitive drug in vivo, sensitive in vitro but not treated with a sensitive drug, or having disease resistant to all drugs tested in vitro. Response and survival for these patient categories were compared using multivariate regression techniques. Patients receiving a sensitive drug, compared with those who though having sensitivity did not, had a higher remission rate (odds ratio, 6.5; 95% CI, 2.91–14.53) and reduced death rate (hazard ratio, 0.29; 95% CI, 0.16–0.53). Having adjusted for all known confounding factors, the results suggest that in vitro drug sensitivity is an important independent prognostic variable to include in future trials, and that the DiSC assay may be a cost-effective use of health resources: the estimated incremental cost-effectiveness was £1,470 per life-year gained. A randomized controlled trial is required to confirm the benefit and estimate reliably the potential impact of assay-guided choice of therapy.

This paper describes the development and testing of a European version of the Appropriateness Evaulation Protocol (AEP). It stemmed from the original U.S. version and the multiple adaptations and modifications made previously and separately by researchers in European countries. The group was particularly concerned with developing a common list of reasons for inappropriate admissions and days of stay, since the principal goal was to enable an understanding of inappropriate hospital use and potential solutions within local health and social care systems. Developing a common EU-AEP included several steps. First, each national instrument was translated from the national language to English. These back translations were compared with each other and with the US-AEP. A working group analyzed the content of the lists of reasons published in the literature and proposed a novel conceptual approach. On the basis of workshop discussions, a draft of a common European version was circulated to each participant for agreement. In the EU-AEP, the clinical criteria for the appropriateness of admission include 10 related to patient condition and five to clinical services. The criteria for the appropriateness of days of care include 10 covering medical services, six for life support/nursing services, and eight related to patient condition. The proposed core list of reasons of inappropriateness distinguish clearly between two concepts: a) the level of care required by the patient; and b) the reason why this level of care was not used. The first list would thus refer to the nature of resources and facilities required, while the second would focus more on the efficient organization of those resources. A validated European tool to assess inappropriate hospital admissions and hospital days of stay and their causes might be used to assess the need for resources for inpatient care as well as for outpatient care. Assessing the reasons for inadequacies might lead also to the examination of organizational questions. Finally, a common tool allows comparisons between countries concerning the frequency of inappropriate admissions and days of stay and their reasons in relation to the different organizations of health care across Europe.

This paper analyzes the cost-effectiveness of screening and treating diabetic retinopathy (DR) by simulating the disease progress continuously with existing data. A new computer simulation based on Monte Carlo techniques and logistic transformation follows cohorts from diabetes onset until death in five care scenarios. For younger-onset patients, ophthalmic care reduces the prevalence of blindness by 52% or greater while savings in disability facilities and production losses surpass direct costs. For older-onset patients, less favorable results appear. Financial benefits surpass costs for juvenile-onset patients. For other patients, the net costs of ophthalmic care seem lower than in other health care programs.

Several new topical agents have been introduced recently and it can be expected that the treatment of glaucoma will change, depending on how effectively these agents control intraocular pressure (IOP). IOP is considered the major risk factor in the development of glaucomatous damage. In order to estimate the impact of these new agents on the cost of treating glaucoma, a simulation model was created to estimate the cost of treating patients with a recent diagnosis of primary open-angle glaucoma or ocular hypertension in different countries. The Markov model is based on retrospective chart reviews in different countries and calculates only cost, not outcome. Results are presented for France and the United Kingdom, where current treatment appeared to be comparable. Average one-year costs per patient with current treatment were FF2,389 (US $389) and £380 (US $627), respectively. Costs with the new treatments were lower than with current therapy.

The results of a field study of three sites that used video to link primary care medical centers to hospitals are reported. The analysis was concerned with identifying the people involved, the tasks carried out in collaboration at each end of the link, and how the different communications facilities helped or hindered. The results are summarized as six task characteristics and their design implications for this model of telemedical consultation are discussed.

The need for better communication and collaboration between health technology assessment agencies led to the formation of an International Network of Agencies for Health Technology Assessment (INAHTA). The network now comprises 27 agencies and has been successful in improving exchange of information and in undertaking joint health technology assessment projects. Issues for the future include possible changes to criteria for membership and identification of resources for more extensive programs.