This special section is the written record of the second National Institute for Clinical Excellence (NICE) conference, which drew together experts in the fields of health technology assessment (HTA) from around the world. It includes a significant perspective from the pharmaceutical industry, whose partnership with the manufacturers of technologies (pharmaceuticals, devices, etc.) is of paramount importance to the successful future of the input of HTA into healthcare delivery. The importance of HTA as the basis of clinical decision making has never been more apparent. All clinicians are aware of the requirement that they provide the most up-to-date health care for their patients, who in turn appropriately consider this as a right. The need to ensure that this care is based on reliable evidence of clinical effectiveness is paramount. In addition, the need for all healthcare systems to consider costs as well as benefits has led to a further imposition on those who provide care to take into account value for money when considering the implementation of a new technology.

Introduction: Many health technologies exhibit some form of learning effect, and this represents a barrier to rigorous assessment. It has been shown that the statistical methods used are relatively crude. Methods to describe learning curves in fields outside medicine, for example, psychology and engineering, may be better.

Methods: To systematically search non–health technology assessment literature (for example, PsycLit and Econlit databases) to identify novel statistical techniques applied to learning curves.

Results: The search retrieved 9,431 abstracts for assessment, of which 18 used a statistical technique for analyzing learning effects that had not previously been identified in the clinical literature. The newly identified methods were combined with those previously used in health technology assessment, and categorized into four groups of increasing complexity: a) exploratory data analysis; b) simple data analysis; c) complex data analysis; and d) generic methods. All the complex structured data techniques for analyzing learning effects were identified in the nonclinical literature, and these emphasized the importance of estimating intra- and interindividual learning effects.

Conclusion: A good dividend of more sophisticated methods was obtained by searching in nonclinical fields. These methods now require formal testing on health technology data sets.

Objectives: The study evaluated the extent to which quality-adjusted life-years (QALYs) and healthy-years equivalents (HYEs) were used in cost-utility studies over the past 20 years (1981–2000) as well as possible changes in the quality of journals reporting cost-utility studies.

Methods: Cost-utility studies were identified through an electronic search. For each study the journal name, date of publication, article's language and research origin, and the journal's impact factor were recorded.

Results: The number of published cost-utility studies increased in the last 20 years but has leveled off in 1997. Most studies were performed in the United States and were published in English. All studies except one used QALYs as an outcome measure. The mean journal's impact factor has changed slightly over the years.

Conclusions: Cost-utility studies would possibly gain more popularity if they were used as a vehicle in the decision-making process regarding healthcare budgets and were more visible in the scientific literature.

We challenge assumptions that have guided much research and policy aimed at understanding and reducing medical practice variation. Paramount is the focus on doctors as the cause of variation to the neglect of other possible influences. Some research literature suggests that patients, families, and the community context of practice may also influence treatment decisions. Failure to question present assumptions, despite weak evidence in support of them, may account for inability to explain persistent practice variation, develop appropriate implementable guidelines, or anticipate the effect on treatment decisions of greater patient involvement. In this paper, we discuss the weak response to the NIH Consensus Conference on early stage breast cancer because it may have reflected these problems. We urge a more complex and more empirical approach in explaining treatment choice and guidelines sensitive to the potential for value differences.

In healthcare decision making, there is an important functional separation between assessment and appraisal. In the U.K. National Health Service (NHS), this distinction is illustrated by the separation of roles between the Health Technology Assessment Programme and the National Institute for Clinical Excellence. However, it can be seen at every level within the healthcare system. Assessment of a technology is a scientific task that synthesizes all relevant evidence on effectiveness and cost-effectiveness; its results are therefore generalizable. Appraisal of the technology is informed by the assessment but adds context-specific judgments on the applicability of the evidence, the feasibility and impact of alternative options, relative priorities, and wider social and ethical aspects. An explicit distinction between assessment and appraisal is helpful in achieving clarity, consistency, and consensus. It also makes clear the need for a wide range of assessment reviews to support decision making by commissioners, providers, and users of health services. Increasingly, the secondary research supported by the NHS R&D Programme is being distributed electronically. It is also being used to identify areas in which further primary research should be commissioned.

Objective: We studied the influence of the methodologic quality of individual trials on the outcome of a landmark meta-analysis on thrombolytic therapy in acute myocardial infarction. From each study we extracted the number of patients in both groups who died in hospital or during follow-up. Methodologic quality was assessed using the Delphi list. We first recalculated pooled odds ratios (ORs) and 95% confidence intervals (CIs), on the studies found and compared them with the original results of Yusuf et al. Next we incorporated the results of quality assessment in five different ways in the calculation of the pooled ORs: a) component analysis; b) visual plot; c) quality score as a threshold score; d) quality score as a weighting factor; and e) cumulative pooling.

Results and Conclusion: No correlation between quality scores and ORs was found. Studies with a proper description of the different quality components provided an estimate close to the true treatment effect. No major differences were found between the results of the five different methods of incorporating the quality scores into the final conclusion.

Objectives: Healthy-years equivalents (HYEs) have been proposed as an evaluative measure with advantages over quality-adjusted life-years (QALYs). The main purpose was to assess the feasibility of eliciting HYEs from patients who have undergone major joint replacement; a secondary objective was to examine relationships with postsurgical health status.

Methods: Pre- and postsurgical reports of perceived comorbidity and current arthritic burden were obtained from 194 patients, using a comorbidity checklist, summary scores from the Western Ontario/McMaster Osteoarthritis Questionnaire (WOMAC), summary scores derived from six Likert scales, and holistic utility scores for the same attributes. After surgery, HYEs for the full across-time health profile were also elicited.

Results: All measures of arthritic burden were sensitive to pre/postsurgical changes (p = .0001), and comorbidity scores were stable. Two HYE subgroups emerged. An HYE-invariant subgroup ascribed full HYEs to their profiles, while reporting higher Likert (t = 2.1309; p = .0344) and utility (s = 4.1504; p = .0001) scores for their postsurgical health state. An HYE-variant subgroup reported HYEs that were weakly but significantly (p < .009) correlated with Likert (r = .30), utility (rs = .25), and comorbidity (r = −.26) scores for their postsurgical state.

Conclusions: Our results indicate that patients can understand the HYE assessment procedures and provide interpretable responses. However, a significant proportion reports invariant HYEs that could inflate estimates of the overall mean HYE. Further exploration of the HYEs reported by different clinical and attitudinal populations is needed before widespread adoption of this measure.

Objectives: The assessment of electronic fetal monitoring (EFM) carried out by the authors in the late 1970s provides an early case of a systematic review of evidence in health technology assessment. This paper identifies lessons pertinent for the present day in this field.

Methods: We reviewed our own files for the description of our assessment and reactions to it. We also reviewed recent literature to evaluate our observations in relation to recent evidence.

Results: Our findings of insufficient evidence of efficacy and concerns about safety have been confirmed by subsequent research. Still, despite findings and recommendations of prominent professional and governmental bodies, EFM continues in widespread use in the United States and Europe and is spreading into developing countries around the world. Aggressive attacks on our assessment as well as our skills and integrity have been mirrored in recent years by criticism of other researchers in health technology assessment.

Conclusions: The case of EFM points to the limitations of assessment without other actions to assure the implementation of results. Health technologies that are accepted by the majority of clinicians in a particular field may require extraordinary efforts to assure appropriate use of technology assessments.

Objectives: We designed a model of diagnostic and therapeutic interventions applied in children with meningeal signs. Using this model, we determined in a cost-utility analysis the consequences for society of different diagnostic strategies in terms of quality-adjusted life-years (QALYs) and costs.

Methods: Data were used from 360 children (0.1–15 years) visiting the pediatric emergency department of the Sophia Children's Hospital Rotterdam, The Netherlands (1988–98) with meningeal signs. Model inputs included probabilities of meningitis and adverse outcome, QALYs for years lived with long-term sequelae, and costs of tests and treatments. Mean outcome measures were costs and effects of diagnostic and therapeutic interventions in children suspected of bacterial meningitis, key determinants of the model outcomes, and evaluation of alternative diagnostic strategies and two vaccination programs in an analysis.

Results: The population comprised 99 children with bacterial meningitis (adverse outcome in 10), 36 with serious other bacterial infections, and 225 with self-limiting diseases. Key determinants were the risk of bacterial meningitis or sequelae, costs of treatment, and long-term morbidity. Minimizing lumbar punctures and empirical treatments using a diagnostic decision rule, without missing a single case of meningitis, was a dominant strategy to actual practice. Vaccination strategies of Streptococcus pneumoniae and Neisseria meningitidis resulted in our model in incremental cost-utility ratios of 401,965 Euro dollar ()/QALY and 22,635/QALY, respectively.

Conclusions: Costs of long-term morbidity of bacterial meningitis largely outweigh diagnostic and treatment costs. Modeling interventions in children at risk of bacterial meningitis should include long-term consequences in terms of costs and QALYs.

Objectives: This paper explores the use of evidence, focusing on economic evidence in particular, in the development of local health policies through an in-depth study of Health Improvement Programmes (HImPs) in England.

Methods: A questionnaire was sent to the person responsible for coordinating the development of the HImP in each of the 102 English health authorities. In addition, semi-structured interviews were conducted with 10 HImP leaders, and a random sample of 26 HImP documents was reviewed using a standard pro forma.

Results: Of the 102 mail questionnaires sent out, 68 (67%) were returned. It was found that those developing HImPs had multiple objectives, only some of which (e.g., efficiency in healthcare provision) would necessarily require evidence. Where evidence was used, this was a mixture of internal (experiential) and external (empirical) evidence, with the balance (66%) being in favor of the latter. Government reports and guidance from the National Institute for Clinical Excellence (NICE), were the main sources of external evidence, rather than published papers. Key barriers to the use of economic evidence were lack of time and availability and the difficulties in synthesizing information at the local level.

Conclusions: Based on responses to our survey, the main ways of increasing the use of evidence in the development of local health policies in England are to produce more evidence-based national guidance and to produce accessible summaries of the available literature for local decision makers.

The technology appraisal program of the National Institute for Clinical Excellence (NICE) was established on April 1, 1999. Its role is to advise the NHS in England and Wales on the clinical effectiveness, cost-effectiveness, and service impact of new and emerging as well as established healthcare technologies. This paper describes the role of HTA in the NICE technology appraisal process, discusses some of the challenges of the use of HTA in national policy making, and considers some of the potential ways forward.

Objectives: The aim was to determine which generations of the evolving technology of magnetic resonance angiography (MRA) are currently of clinical relevance in two clinical applications. Our purpose was to plan a systematic review that would be valuable both to purchasers driven by cost-effectiveness and to practicing clinicians.

Methods: Information was gathered from a search of major bibliographic databases, from a short questionnaire sent to 500 U.K. vascular radiologists and vascular surgeons, and from local clinical experts. We asked which of the MRA techniques were currently used and, assuming availability, what would be their technique of choice.

Results: There were 206 published articles that satisfied preliminary inclusion criteria: 69 discussed 2D time of flight (TOF); 47, 3D TOF; and 38, contrast-enhanced techniques. There were 162 questionnaires returned (60 radiologists, 102 surgeons). Of the total respondents, 77/162 (48%) used MRA in the assessment of carotid artery stenosis; 47/77 (61%) used 2D TOF; 32/77 (42%), 3D TOF; and 26/77 (34%), contrast-enhanced techniques. Thirty-five of 162 (22%) respondents used MRA in the assessment of peripheral vascular disease (PVD); 15/35 (43%) used 2D TOF, 4/35 (11%) used 3D TOF, and 22/35 (63%) used contrast-enhanced techniques. For those wishing to use MRA, contrast-enhanced techniques were the method of choice.

Conclusions: The TOF methods that represent earlier generations of the technology remain clinically relevant, and will therefore be included in our systematic review. To ensure complete and relevant coverage in reviews of other evolving technologies, it would be advisable to obtain data for guidance in a similar way.

Health technology assessment (HTA) grew from a need recognized by researchers concerned about the effectiveness of health services. They were later joined by policy makers in search of valid information about the costs and benefits of investments in health care. The history of HTA shows that this need appeared in many countries at nearly the same time.

Objectives: Although psychiatric comorbidity is relevant for a number of diseases, it is often ignored in technology assessment. This study examines the service use rate in mental healthcare facilities and related costs for stroke patients discharged from the University Hospital Maastricht between 1987 and 1995.

Methods: Through anonymous record linkage, the medical registration of the hospital and the registration of the Maastricht Mental Health Case Register were linked.

Results: Linkage succeeded for 16% of the 2,020 stroke patients, indicating that these patients used mental health services during a 10-year period around the stroke (±5 years). Of the users' group, 88% had a mental healthcare contact following stroke. Regression analysis shows that age, length of hospital stay, and mental healthcare contact before stroke are associated with mental healthcare use after stroke. It is remarkable in that there is already an increase in the consumption of mental health care in the prodromal phase just before the stroke occurred. When comparing costs before and after stroke, the outpatient costs increased on average by \epsfbox{cj108-4-euro.eps}42.64, semi-institutionalized costs increased on average by \epsfbox{cj108-4-euro.eps}208.10, and intramural costs by \epsfbox{cj108-4-euro.eps}1,189.21. The total increase in costs is \epsfbox{cj108-4-euro.eps}1,439.95. For all mental healthcare facilities, the increase in costs is significant.

Conclusions: No study so far has revealed the total costs of mental healthcare facilities following stroke. Extrapolating these costs to the Netherlands illustrates that stroke patients have a high psychiatric comorbidity, inducing about 1.3% of total mental healthcare costs.

Objectives: Systematic review of the clinical and cost-effectiveness of donepezil, rivastigmine, and galantamine for people suffering from Alzheimer's disease.

Methods: Sixteen electronic databases (including MEDLINE, the Cochrane Library, and Embase) and bibliographies of related papers were searched for published/unpublished English language studies, and experts and pharmaceutical companies were consulted for additional information. Randomized controlled trials (RCTs) and economic studies were selected. Clinical effectiveness was assessed on measurement scales assessing progression of Alzheimer's disease on the person's global health, cognition, functional ability, behavior and mood, and quality of life. Cost-effectiveness was presented as incremental cost per year spent in a nonsevere state (by Mini Mental Health State Examination) or quality-adjusted life-year.

Results: Twelve of 15 RCTs included were judged to be of good quality. Although donepezil had beneficial effects in Alzheimer's patients on global health and cognition, rivastigmine on global health, and galantamine on global health, cognition, and functional scales, these improvements were small and may not be clinically significant. Measures of quality of life and behavior and mood were rarely assessed. Adverse effects were usually mild and transient. Cost-effectiveness base case estimates ranged from £2,415 savings to £49,476 additional cost (1997 prices) per unit of effect for donepezil and a small savings for rivastigmine. Estimates were not considered robust or generalizable.

Conclusions: Donepezil, rivastigmine, and galantamine appear to have some clinical effect for people with Alzheimer's disease, although the extent to which these translate into real differences in everyday life remains unclear. Due to the nature of current economic studies, cost-effectiveness remains uncertain and the impact on different care sectors has been inadequately investigated. Further research is needed to establish the actual benefits of acetylcholinesterase inhibitors (AChEls) for people with Alzheimer's disease and their caregivers, the relationship of these changes to clinical management, and careful prospective evaluation of resource and budgetary consequences.

The Bayesian approach to statistics has been growing rapidly in popularity as an alternative to the frequentist approach in the appraisal of heathcare technologies in clinical trials. Bayesian methods have significant advantages over classical frequentist statistical methods and the presentation of evidence to decision makers. A fundamental feature of a Bayesian analysis is the use of prior information as well as the clinical trial data in the final analysis. However, the incorporation of prior information remains a controversial subject that provides a potential barrier to the acceptance of practical uses of Bayesian methods. The pur pose of this paper is to stimulate a debate on the use of prior information in evidence submitted to decision makers. We discuss the advantages of incorporating genuine prior information in cost-effectivene ss analyses of clinical trial data and explore mechanisms to safeguard scientific rigor in the use of such prior information.

Objective: The objective of this study was to examine the economics of administering calcium and vitamin D3 to post-menopausal women in Sweden. We focus primarily on the cost-effectiveness of treating older women for whom clear evidence of efficacy is available. We supplement this information, however, with estimates of the cost-effectiveness of treating certain high-risk groups of younger women, while acknowledging the greater uncertainty involved.

Methods: We developed a Markov model for analyzing the occurrence and timing of hip fractures, based almost entirely on peer-reviewed data from Sweden. In a 3-year randomized clinical trial, the combination of calcium and vitamin D3 was shown to reduce the risk of hip fractures by 27%. Costs for treating hip fractures were based on 1,080 women who were hospitalized in Stockholm.

Results: Treatment of 70-year-old women was cost saving at efficacy as low as two-thirds that seen in the clinical trials, and upwards. Even at modest rates of efficacy, treatment of the high-risk 50- and 60-year-old cohorts was generally cost-effective and in some cases even cost saving. Particularly cost-effective was treatment of women with identified osteoporosis or a maternal family history of hip fracture.

Conclusion: Simulation results suggest a role for lifetime treatment of older women with calcium and vitamin D3 in Sweden. While there is more uncertainty underlying the treatment of younger women, our simulation results suggest that treatment may also be cost saving or at least cost-effective for many cohorts of high-risk 50- and particularly 60-year-old women, in particular those with osteoporosis or a maternal family history of hip fracture.

Objectives: Comparative economic evaluations of chemotherapy administered in hospital day-care units or in the home are relatively scarce. Furthermore, most existing evaluations do not include methodologic studies. This study seeks to compare the costs of anticancer chemotherapy with hospital at-home care versus a hospital day-care unit in the Rhône-Alpes region of France.

Methods: This study is based on a randomized controlled crossover trial that included 42 patients, to whom chemotherapy courses were alternatively given in both settings. All cost categories were taken into account according to microcosting methods. A detailed assessment was performed on coordination and health care in both structures (marginal costs and average costs), from the viewpoint of society.

Results: The marginal cost for one chemotherapy administration was significantly higher with hospital at-home care than in the hospital day-care unit ($232.5 vs. $157, p < .0001). Conversely, the average cost was significantly lower with home care than at the hospital ($252.6 vs. $277.3, p = .0002).

Conclusions: The results show that the interest of developing home care in anticancer chemotherapy is questionable regarding costs. In the French healthcare system, where there is a surplus of hospital beds, marginal costs seem to be more relevant indicators in most cases than average costs.

Increasingly, health technology assessment (HTA) is used to aid decisions on the reimbursement of pharmaceuticals or recommendations for their use. The pharmaceutical industry seeks to work in partnership with HTA agencies; however, this presents a number of challenges. Clinical trials will need to include appropriate measures that capture economic and patient benefits as well as relevant clinical endpoints, and the industry will want to seek international harmonization of the many guidelines for economic evaluation. The problem of demonstrating cost-effectiveness of a product before it is available for use must be addressed, possibly by conditional reimbursement to allow collection of real world evidence. It is also important that reimbursement decision makers minimize bias, play fair, and adhere to the written rules they issue. If the industry fairly demonstrates the value of a product using the best available evidence, HTA agencies should be transparent in the rationale for their recommendations.

Objectives: The great interest focused on home care technologies during the last decade resulted from its potential to cut costs. However, the reallocation of costs between healthcare providers and social welfare providers, and the indirect costs of informal care, are not as frequent topics of discussion. The aim of this paper is to discuss different models for estimating the costs of informal care in the home care setting in economic appraisals.

Methods: The outcome of using different models for estimating indirect costs was illustrated using empirical data regarding the time spent by informal caregivers in providing care in a group of home care patients (n = 59). The models used comprise different interpretations of the traditional human capital approach and the friction cost model.

Results and Conclusions: Informal care is an important component in home care. The inclusion of indirect costs of informal care in economic appraisals will have implications for the cost-effectiveness of home care, since it will raise costs depending on the model used for estimating indirect costs. In this study we have shown that indirect costs estimated by the friction cost model only amount to 18% to 44% of the cost when the human capital approach is used. The results indicate that, regardless of the method used to estimate indirect costs, the cost of informal care in evaluations of home care programs is often underestimated due to the exclusion of indirect costs.