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.

Objectives: The aim of this study was to review studies reporting cost-effectiveness of exercise-based interventions in treatment of various diseases.

Methods: Systematic literature search using several databases. Abstracts initially screened independently by two authors, full-text articles again evaluated by two authors, who decided whether an article should be included. Included were scientifically valid articles describing controlled studies that included an exercise-based intervention in the treatment of an established medical condition, and also reported on the cost-effectiveness of the intervention, or its effect on the utilization of health services. Quality was assessed with an established approach.

Results: A total of 914 articles were identified, of them 151 were obtained for closer review. Sixty-five articles describing sixty-one studies were included. Most (82 percent) were randomized trials. Twenty-eight studies dealt with musculoskeletal disorders, fifteen with cardiology, four with rheumatic diseases, four with pulmonary diseases, three with urinary incontinence, and two with vascular disorders. There was one study each in the fields of oncology, chronic fatigue, endocrinology, psychiatry, and neurology. Exercise interventions in musculoskeletal disorders were deemed to be cost-effective in 54 percent, in cardiology in 60 percent, and in rheumatic diseases in 75 percent of the cases. There was some evidence that exercise might be cost-effective in intermittent claudication, breast cancer patients, diabetes, and schizophrenia.

Conclusions: The number of studies assessing cost-effectiveness of exercise interventions in various diseases is still limited. The results show large variation but suggest that some exercise interventions can be cost-effective. Most convincing evidence was found for rehabilitation of cardiac and back pain patients; however, even in these cases, the evidence was partly contradictory.

The Problem: There is a shortage and maldistribution of medically trained health professionals to deliver cost-effective maternal and child health (MCH) services. Hence, cost-effective MCH services are not available to over half the population of Uganda and progress toward the Millennium Development Goals for MCH is slow. Optimizing the roles of less specialized health workers (“task shifting”) is one strategy to address the shortage and maldistribution of more specialized health professionals.

Policy Options: (i) Lay health workers (community health workers) may reduce morbidity and mortality in children under five and neonates; and training for traditional birth attendants may improve perinatal outcomes and appropriate referrals. (ii) Nursing assistants in facilities might increase the time available from nurses, midwives, and doctors to provide care that requires more training. (iii) Nurses and midwives to deliver cost-effective MCH interventions in areas where there is a shortage of doctors. (iv) Drug dispensers to promote and deliver cost-effective MCH interventions and improve the quality of the services they provide. The costs and cost-effectiveness of all four options are uncertain. Given the limitations of the currently available evidence, rigorous evaluation and monitoring of resource use and activities is warranted for all four options.

Implementation Strategies: A clear policy on optimizing health worker roles. Community mobilization and reduction of out-of-pocket costs to improve mothers’ knowledge and care-seeking behaviors, continuing education, and incentives to ensure health workers are competent and motivated, and community referral and transport schemes for MCH care are needed.

Objectives: We assessed the impacts of a Citizens’ Reference Panel on the deliberations of a provincial health technology advisory committee and its secretariat, which produce, recommendations for the use of health technologies in Ontario, Canada.

Methods: A fourteen-member citizens’ reference panel was convened five times between February 2009 and May 2010 to participate in informed, facilitated discussions to inform the assessment of individual technologies and provincial health technology assessment processes more generally. Qualitative data collection methods were used to document observed and perceived impacts of the citizens’ panel on the health technology assessment (HTA) process.

Results: Panel impacts were observed for all technologies reviewed, at two different stages in the HTA process, and represented macro- (raising awareness) and micro-level (informing recommendations) impacts. These impacts were shaped by periodic opportunities for direct and brokered exchange between the Panel and the expert advisory committee to clarify roles, foster accountability, and build trust. Our findings offer new insights about one of the main considerations in the design of deliberative participatory structures—how to maintain the independence of a citizens’ panel while ensuring that their input is considered at key junctures in the HTA process.

Conclusions: Citizens’ panels can exert various impacts on the HTA process. Ensuring these types of structures include opportunities for direct exchange between citizens and experts, to clarify roles, promote accountability, and build trust will facilitate their impacts in a variety of settings.

This reflection on the history of the International Society of Technology Assessment in Health Care is an effort to describe the creation of the Society and its first 10 years of activity. Without analyzing the forces that spurred the growth of technology assessment internationally or linking events, policies, and changes in the various countries, this essay focuses on the persons and events that surrounded the birth and growth of the Society in the past decade.

A cost-utility analysis (CUA) was applied to group living for dementia patients. A Markov-model of an expected life-length of 8 years was used. Forty-six patients in group living were compared to 39 patients living at home by inclusion and 23 institutionalized patients. When the cost per gained quality-adjusted life-year (QALY) was calculated, the group living alternative was the most favorable for the patients, giving a cost per paired QALY of US dollars > 0. In the extensive sensitivity analysis the main result was consistent but methodological problems were indicated.

Objectives: Investments in health research should lead to improvements in health and health care. This is also the remit of the main HTA program in the Netherlands. The aims of this study were to assess whether the results of this program have led to such improvements and to analyze how best to assess the impact from health research.

Methods: We assessed the impact of individual HTA projects by adapting the “payback framework” developed in the United Kingdom. We conducted dossier reviews and sent a survey to principal investigators of forty-three projects awarded between 2000 and 2003. We then provided an overview of documented output and outcome that was assessed by ten HTA experts using a scoring method. Finally, we conducted five case studies using information from additional dossier review and semistructured key informant interviews.

Results: The findings confirm that the payback framework is a useful approach to assess the impact of HTA projects. We identified over 101 peer reviewed papers, more than twenty-five PhDs, citations of research in guidelines (six projects), and implementation of new treatment strategies (eleven projects). The case studies provided greater depth and understanding about the levels of impact that arise and why and how they have been achieved.

Conclusions: It is generally too early to determine whether the HTA program led to actual changes in healthcare policy and practice. However, the results can be used as a baseline measurement for future evaluation and can help funding organizations or HTA agencies consider how to assess impact, possibly routinely. This, in turn, could help inform research strategies and justify expenditure for health research.

Objectives: The aim of this study was to examine the potential cost-effectiveness of self-managed computer therapy for people with long-standing aphasia post stroke and to estimate the value of further research.

Methods: The incremental cost-effectiveness ratio of computer therapy in addition to usual stimulation compared with usual stimulation alone was considered in people with long-standing aphasia using data from the CACTUS trial. A model-based approach was taken. Where possible the input parameters required for the model were obtained from the CACTUS trial data, a United Kingdom-based pilot randomized controlled trial that recruited thirty-four people with aphasia and randomized them to computer treatment or usual care. Cost-effectiveness was described using an incremental cost-effectiveness ratio (ICER) together with cost-effectiveness acceptability curves. A value of information analysis was undertaken to inform future research priorities.

Results: The intervention had an ICER of £3,058 compared with usual care. The likelihood of the intervention being cost-effective was 75.8 percent at a cost-effectiveness threshold of £20,000 per QALY gained. The expected value of perfect information was £37 million.

Conclusions: Our results suggest that computer therapy for people with long-standing aphasia is likely to represent a cost-effective use of resources. However, our analysis is exploratory given the small size of the trial it is based upon and therefore our results are uncertain. Further research would be of high value, particularly with respect to the quality of life gain achieved by people who respond well to therapy.

Objectives: The aim of this study was to explore the use of surrogate outcomes—a substitute outcome that predicts final patient-related outcomes—in cost-effectiveness models (CEM) within health technology assessment (HTA) reports and provide guidance for their future use.

Methods: Our sampling frame was all UK HTA Program monograph series reports published in 2005 and 2006. Reports were included if they addressed a treatment effectiveness/efficacy question and included a CEM based on a surrogate outcome. The two authors independently applied inclusion and exclusion criteria, and the following data was extracted from included reports: source of surrogate outcome, level of evidence for validation of the surrogate outcomes, methods used in report to quantify link between surrogate outcome and final outcome, and consideration of the uncertainty associated with using surrogate outcomes in the results or conclusions of report.

Results: Of 100 HTA reports, 35 complied with the inclusion criteria. Of these, four (11 percent) reports included a CEM based on a surrogate outcome. All four reports sourced treatment-related changes in surrogate outcome through a systematic review of the literature. One provided Level 1 surrogate evidence (randomized controlled trial data showing a strong association between the change in surrogate outcome and change final outcome); two reported Level 2 evidence (observational study data); and one provided Level 3 evidence (disease natural/ history data). The transparency of quantification and exploration of uncertainty of the surrogate and final outcome relationship varied considerably across all four reports.

Conclusions: Recommendations are made for the use of surrogate outcomes in future HTA reports.

This paper reports the results of a study of the association between volume of activity and patient outcome in 26 intensive care units in the United Kingdom. Hospital fatality rates showed a statistically significant (p =.016) negative association with volume. However, mean APACHE II scores, as a measure of the severity of case mix, were also negatively associated with volume (p =.021). Thus, one explanation of the lower death rates at higher volumes is that larger units admit less severely ill patients. For patients admitted immediately after surgery, the correlation between severity standardized mortality ratios and volume (while not significant, p <.1) suggests there may be a volume-output effect unexplained by severity.

Objectives: To introduce a health-related quality of life measure for home care and institutional long-term care settings based on the Minimum Data Set (MDS) and the Health Utilities Index Mark 2 (HUI2).

Methods: Health attributes of Health Related Quality of Life (HRQOL) were identified, and suitable constructs were determined. Items from the MDS were mapped to the HUI2. Scores for the Minimum Data Set Health Status Index (MDS-HSI) were calculated using the HUI2 scoring function. Measurement properties are examined and reported. HRQOL scores were compared across study populations and to an external reference population. Random samples were drawn from long-term care clients in private households (n=377), supportive housing apartments (n=80), two residential care facilities (n=166), and a chronic care hospital (n=274) in Ontario, Canada. All sampled residents were assessed for health-related items using the MDS.

Results: The MDS-HSI results provide preliminary evidence of good validity. Institutional populations had lower overall HRQOL scores than community populations. Comparisons to existing Canadian national data support construct validity.

Conclusions: The MDS-HSI provides a summary outcome measure and an indicator of health status in the six supporting attributes. Longitudinal research is required to assess the sensitivity of the measure to changes over time. Further research is also required to establish the consistency between the preference weights used in this application of the HUI2 and those that would be derived from a frail elderly population.This research was supported by the Seniors Independence Program (grant 4687-06-93-458) and the Providence Centre Foundation. Thanks to Copernicus Lodge, Providence Centre, and the Red Cross Homemaker Program for participating in this study. Also thanks to Roger Roberge and Dan Dekoker from Statistics Canada for their help in obtaining and analyzing the NPHS data. International copyright for the MDS-NH and MDS-HC is held by interRAI. International copyright for HUI2 and HUI3 materials are held by Health Utilities, Inc.

The practice of health care technology assessment involves ethical considerations in all of its varied functions and techniques. Ethical issues in technology assessment can be grouped into the broad categories of normative concepts, diagnosis, prevention and therapy, research and the advancement of knowledge, and allocation of resources. Moreover, the ethics of the assessment process itself must be evaluated in terms of the integrity of the project's goals, procedures, and effects, and evaluators’ open and self-critical acknowledgment of their purposes. As a relatively new field, technology assessment can benefit from using a variety of analytic approaches as it works to develop its own methods for evaluating ethical issues related to technology.

Economic evaluations of Pharmaceuticals are increasingly being conducted in conjunction with randomized phase III clinical trials to meet the demand for pharmacoeconomic data when new products are launched. While the need for such data is often global, the trials in which relevant information may be collected are often conducted in only one or a limited number of countries. A critical issue is how data from pivotal clinical trials in one setting can serve as the basis for pharmacoeconomic evaluations in others. We address this issue and report on four economic evaluations that we undertook in conjunction with a recent U.S. phase III clinical trial of recombinant human deoxyribonuclease (rhDNase), which is used to improve pulmonary function in patients with cystic fibrosis (CF). The objective of these evaluations was to estimate the potential impact of rhDNase therapy in France, Germany, Italy, and the United Kingdom on the direct costs of medical care for the treatment of respiratory tract infections (RTIs) in patients with CF. Analyses of economic impact were undertaken

Objectives: A mapping exercise was undertaken to determine how HTA is being described and conducted across the International Network of Agencies for Health Technology Assessment (INAHTA), with the aim of harmonizing terminologies and approaches.

Methods: Three progressive surveys were undertaken. In 2010, INAHTA agencies were asked to provide details on all of their HTA products. In 2013, additional information was sought on key methodological characteristics of five of the most common HTA product types. Subsequently, final agreement was sought on three proposed product types.

Results: Forty-five HTA agencies responded to at least one of the surveys. In 2010, twenty-one agencies reported publishing over seventy named HTA products. Core domains associated with full HTA reports were reported by a third of agencies but were labeled differently, so products were classified according to product type (n = 17). Agencies producing short, tailored products increased between 2010 and 2013, with the publication of rapid reviews doubling from 33 percent to 66 percent. In 2013, half of the agencies adapted their common HTA products from documents produced by other agencies. A consensus (>70 percent) was achieved on definitions for HTA reports, mini-HTAs, and rapid reviews.

Conclusions: The product label for an HTA is not always indicative of its content. Terminology has, therefore, been agreed to make explicit the trade-off between rigor and timeliness in three common HTA product types. An INAHTA Product Type (IPT) Mark has been created to identify each of these. It is hoped this will further facilitate HTA adaptation between agencies and reduce duplication of effort.

Objectives: To develop and validate a paper-based instrument that is simple to administer and produces a reliable estimate of patient standard gamble (SG) utilities for current health status.

Methods: A 1-page paper questionnaire instrument, paper standard gamble (PSG), was designed to estimate SG utilities. We performed two studies to assess the validity of PSG. First we compared PSG and SG utilities for current health in patients with prostate cancer. They randomly received either PSG followed by SG or vice versa, always with an intervening SF-12. In the second validity study, we assessed the test-retest reliability of PSG by administering it to prostate cancer patients twice, at least 2 weeks apart.

Results: In the first study, utilities were assessed in 64 men (32 per SG/PSG order group). A paired-comparison t test suggested no difference between SG and PSG (mean difference = −0.007; 95% confidence interval (CI), $-$0.022 to 0.008). The concordance correlation coefficient was 0.92 (95% CI, 0.79 to 0.99). In the second study, test and retest PSGs were available for 184 patients. The concordance correlation coefficient was 0.88 (95% CI, 0.73 to 0.94).

Conclusions: These data suggest that PSG may serve as a reliable substitute for SG when current health utility is of interest. PSG may have particular advantages for acquisition of health-related quality-of-life data in longitudinal studies.

Objectives: We sought to evaluate patient involvement (consultation and direct participation) in the assessment of alternative measures to restraint and seclusion among adults in short-term hospital wards (in psychiatry) and long-term care facilities for the elderly.

Methods: We conducted individual semi-structured interviews with thirteen stakeholders: caregivers, healthcare managers, patient representatives, health technology assessment (HTA) unit members, researchers, and members of the local HTA scientific committee. Data were collected until saturation. We carried out content analysis of two HTA reports and four other documents that were produced in relation with this HTA. We also used field notes taken during formal meetings and informal discussions with stakeholders. We performed thematic analysis based on a framework for assessing patient involvement in HTA. We then triangulated data.

Results: For the majority of interviewees, patient consultation enriched the content of the HTA report and its recommendations. This also made it possible to suggest other alternatives that could reduce the use of restraint and seclusion and helped confirm some views and comments from healthcare professionals consulted in this HTA. The direct participation of patient representatives enabled rephrasing of some findings so as to bring the patient perspective to the HTA report.

Conclusions: Patient consultation was seen as having directly influenced the content of the HTA report while direct participation made it possible to rephrase some findings. This is one of few studies to assess the impact of patient involvement in HTA and more such studies are needed to identify the best ways to improve the input of such involvement.

Objectives: We explore how broader aspects of a treatment's value and the impact of the condition on patients not captured by routine health technology assessment (HTA) methods using clinical and economic evidence, defined as “other considerations,” may influence HTA processes in different settings.

Methods: Countries included were England, Scotland, Sweden, and France. Data sources were the publicly available reports on HTA recommendations. Ten drugs with European Medicines Agency orphan designation and appraised in England were selected. Qualitative thematic analysis was used to systematically identify and code all “other considerations” based on a previously developed methodological framework, which also coded whether it was provided by stakeholders, and how it influenced the decision.

Results: A classification framework of scientific and social value judgments was developed and used throughout the study. A total of 125 “other considerations” were identified and grouped into ten subcategories based on the information provided. Eighteen to 100 percent of these, depending on the agency, were put forward as one of the main reasons for the final decision potentially contributing to accepting a higher incremental cost-effectiveness ratio or uncertain evidence. Some of these were nonquantified or nonelicited and pertained to the assessor's judgment. A taxonomy of these value judgments was created to be used in future cases. Results also contributed to better defining the determinants of social value and improving accountability for reasonableness.

Conclusions: The systematic identification of the scientific and social value judgments enables to better understanding the dimensions of value, which can be used to improve their transparency and consistent use across decisions and settings.