The ethical introduction of genome-based information and technologies into public health.

With the human genome project running from 1989 until its completion in 2003, and the incredible advances in sequencing technology and in bioinformatics during the last decade, there has been a shift towards an increase focus on studying common complex disorders which develop due to the interplay of many different genes as well as environmental factors. Although some susceptibility genes have been identified in some populations for disorders such as cancer, diabetes and cardiovascular diseases, the integration of this information into the health care system has proven to be much more problematic than for single gene disorders. Furthermore, with the 1000$ genome supposedly just around the corner, and whole genome sequencing gradually being integrated into research protocols as well as in the clinical context, there is a strong push for the uptake of additional genomic testing. Indeed, the advent of public health genomics, wherein genomics would be integrated in all aspects of health care and public health, should be taken seriously. Although laudable, these advances also bring with them a slew of ethical and social issues that challenge the normative frameworks used in clinical genetics until now. With this in mind, we highlight herein 5 principles that are used as a primer to discuss the ethical introduction of genome-based information and genome-based technologies into public health.

The contribution of health technology assessment, health needs assessment, and health impact assessment to the assessment and translation of technologies in the field of public health genomics.

The European Union has named genomics as one of the promising research fields for the development of new health technologies. Major concerns with regard to these fields are, on the one hand, the rather slow and limited translation of new knowledge and, on the other hand, missing insights into the impact on public health and health care practice of those technologies that are actually introduced. This paper aims to give an overview of the major assessment instruments in public health [health technology assessment (HTA), health needs assessment (HNA) and health impact assessment (HIA)] which could contribute to the systematic translation and assessment of genomic health applications by focussing at population level and on public health policy making. It is shown to what extent HTA, HNA and HIA contribute to translational research by using the continuum of translational research (T1-T4) in genomic medicine as an analytic framework. The selected assessment methodologies predominantly cover 2 to 4 phases within the T1-T4 system. HTA delivers the most complete set of methodologies when assessing health applications. HNA can be used to prioritize areas where genomic health applications are needed or to identify infrastructural needs. HIA delivers information on the impact of technologies in a wider scope and promotes informed decision making. HTA, HNA and HIA provide a partly overlapping and partly unique set of methodologies and infrastructure for the translation and assessment of genomic health applications. They are broad in scope and go beyond the continuum of T1-T4 translational research regarding policy translation.

An interview study of phenotypic characterization of genetically-modified mice.

An interview study was carried out with the aim of clarifying the reasons for the limited use of phenotypic characterization of genetically-modified mice (GMM) and identifying issues hindering its implementation. A total of 15 users of GMM participated in semi-structured face-to-face interviews, which were audio-taped and transcribed. The results were extracted using content analysis by theme. The investigation confirmed that few animals were systematically phenotyped and an observational approach was found to be widespread. The primary interest of the interviewees was phenotyping for impaired animal welfare. The concept of phenotyping was widely understood and perceived as a scientific advantage. The comprehensiveness of the protocols and the resources required for phenotyping were seen as problematic. All participants addressed this issue, be it regarding lack of time, money or expertise. Also, among the negative statements were worries about the capability of the available protocols to produce the information needed by the individual scientist. Phenotyping was predicted to become much more widespread in the future and its success was expected to depend on the development of reliable, fast and inexpensive methods. The study identified different aims of phenotyping and the suitability of the published protocols for these purposes was discussed. The contradiction between the limited use of characterization and its advantages was also discussed and proposals for the improvement of future phenotyping strategies are formulated.

Reimbursement decision-making and prescription patterns of glitazones in treatment of type 2 diabetes mellitus patients in Denmark.

There are marked differences between countries with regard to reimbursement decision-making, yet few studies have tried to understand this process and its consequences by a detailed analysis of the local context and decision-making structure. This article describes reimbursement decision-making and subsequent prescribing patterns of new pharmaceuticals by means of a case study on glitazones in treatment of type 2 diabetes mellitus patients in Denmark. The study shows that institutional arrangements, providing the context in which evidence is used, are highly important for understanding the reimbursement decision-making process. In particular the Danish Medicines Agency (DMA) has shaped the decision to reimburse glitazones on the basis of physician-mediated requests of individual patients. Relatively few patients have been prescribed glitazones since their introduction in 2000, suggesting that individual reimbursement may be an effective instrument in controlling overall expenditure of selected pharmaceuticals, although in the case of glitazones this has likely been achieved at the expense of equality in access to the products. The discussion focuses on the generalizability of the findings to both other pharmaceuticals in the individual reimbursement scheme in Denmark, and to other countries that are trying to balance the need to control overall pharmaceutical care expenditure with the need to secure equality in access to new drugs with therapeutic added value.

Defining cancer patients as being in the terminal phase: who receives a formal diagnosis, and what are the effects?

PURPOSE: Physicians either do not define cancer patients as being terminal, or their prognostic estimates tend to be optimistic. This might affect patients' appropriate and timely referral to specialist palliative care services or can lead to unintended acute hospitalization. PATIENTS AND METHODS: We used the Danish Cancer Register and four administrative registers to perform a retrospective cohort study in 3,445 patients who died as a result of cancer. We used the Danish "terminal declaration" issued by a physician as a proxy for a formal terminal diagnosis (prognosis of death within 6 months). The terminal declaration gives right to economic benefits and increased care for the dying. We investigated patient-related factors of receiving an explicit terminal diagnosis by logistic regression and then analyzed the effects of such a diagnosis on admission rate per week and place of death. RESULTS: Thirty-four percent of patients received a formal terminal diagnosis. Age of > or = 70 years (odds ratio [OR], 0.44; 95% CI, 0.34 to 0.56; P < .001), women (OR, 0.81; 95% CI, 0.69 to 0.96; P = .02), hematologic cancer (OR, 0.20; 95% CI, 0.09 to 0.41; P < .001), and a less than 1-month survival time (OR, 0.10; 95% CI, 0.07 to 0.15; P < .001) were associated with a lesser likelihood of receiving a formal terminal diagnosis. Explicit terminal diagnosis was associated with lower admission rate and an adjusted OR of hospital death of 0.25 (95% CI, 0.21 to 0.29). CONCLUSION: Women and the elderly were less likely to receive a formal terminal diagnosis. The formal terminal diagnosis reduced hospital admissions and increased the possibilities of dying at home.

[Initiating insulin therapy in patients with diabetes mellitus type 2: in a transmural setting is at least as effective as in an outpatient setting; a retrospective study with a 4-year follow-up]. / Het instellen op insuline van patiënten met diabetes mellitus type 2: in een transmurale organisatievorm minstens even effectief als poliklinisch; een retrospectief onderzoek met 4 jaar follow-up.

OBJECTIVE: Assessing whether the initiation of insulin therapy in patients with diabetes mellitus type 2 can be delivered as effectively in a structured transmural care model as in the more usual outpatients structure. DESIGN: Retrospective comparative cohort study. METHOD: In 1997 data were collected from 52 patients with diabetes mellitus type 2 all of whom were above 40 years of age and transferred to insulin therapy in 1993: 25 in a transmural care setting and 27 in an outpatients setting, both in Amsterdam, the Netherlands. Both groups were treated according to one protocol concerning the initiation and monitoring of insulin therapy, treatment goals and follow-up. Outcome measures were: percentage of glycated haemoglobin (HbA1c), health status, self-care behaviour and patient satisfaction. In 1993 the mean age was (transmural/outpatients setting): 67.5/65.3 years; percentage of men: 32%/48%; mean duration of diabetes: 7.3/10.6 years; HbA1c: 9.1%/9.3%; mean body mass index: 27.4/29.1 kg/m2. RESULTS: In the period 1993-1997 the mean HbA1c decreased from 9.1% to 7.2% in the transmural care group and from 9.3% to 7.6% in the outpatients care group (both: p = 0.000). The percentage of patients with poor glycaemic control (HbA1c > 8%) decreased from 60 to 8 in the transmural care group and from 59 to 15 in the outpatients care group. The percentage of patients with good glycaemic control (HbA1c < 7%) increased from 4 to 52 in the transmural care group and from 11 to 30 in the outpatients care group. No statistically significant differences were found between the patient groups with respect to health status, self-care behaviour and patient satisfaction. CONCLUSION: The transfer of patients with diabetes mellitus type 2 insulin therapy in a shared care setting was at least as effective as in an outpatients setting.

Timing of adoption of laparoscopic cholecystectomy in Denmark and in The Netherlands: a comparative study.

Laparoscopic cholecystectomy (LC) has diffused rapidly in most industrialised countries. The aim of this study has been to analyse the impact of different hospital characteristics on the hospital adoption of LC in Denmark and The Netherlands. Data on the timing of the adoption of LC and hospital characteristics (hospital size, teaching status and location) were retrieved in both countries. Proportional hazard regression was used to analyse different multivariate models. A total of 59 Danish and 109 Dutch hospitals adopting LC were identified. The multivariate analyses showed that increased hospital size was associated with relatively early adoption of LC in Denmark. Neither this nor other hospital characteristics influenced the timing of adoption in The Netherlands. As in other countries studied, hospital size is identified as an important factor in hospital adoption, whereas teaching status and location play a more limited role. The study shows that a multivariate method, such as the proportional hazard regression, can be used to elucidate differences among countries of the impact of different factors on the adoption of medium-ticket technologies like LC. Such multinational comparisons provide valuable information for health policy and planning.

Perioperative enteral nutrition and quality of life of severely malnourished head and neck cancer patients: a randomized clinical trial.

BACKGROUND AND AIMS: This study evaluated the use of perioperative nutritional support on Quality of Life (QOL) in malnourished head and neck cancer patients undergoing surgery. METHODS: 49 Malnourished (weight loss >10%) head and neck cancer patients who were included in a nutrition intervention trial were randomized to receive either no preoperative and standard postoperative tube-feeding (group I), standard preoperative and postoperative tube-feeding (group II) or arginine-supplemented preoperative and postoperative tube-feeding (group III). Of these patients, 31 completed a full QOL assessment on the first day of preoperative nutritional support, one day before surgery, and 6 months after surgery. Both a disease-specific (EORTC QLQ-C30) and a generic questionnaire (COOP-WONCA) were used. One way analysis of variance (ANOVA) and the Kruskal-Wallis test were applied for testing differences in scores between groups. RESULTS: Between baseline and the day before surgery, both preoperatively fed groups revealed a positive change for the dimensions physical and emotional functioning and dyspnea (with significance in group II, P=0.050,0.031,0.045 respectively). Group III showed a negative change in appetite (P=0.049). Between baseline and 6 months after surgery, there were no differences between group I and both pre-fed groups. There were no differences in favour of group III compared to group II. CONCLUSION: Enteral nutrition improves QOL of severely malnourished head and neck cancer patients in the period preceding surgery. No benefit of preoperative enteral feeding on QOL could be demonstrated 6 months after surgery.

Identification and priority setting for health technology assessment in The Netherlands: actors and activities.

This article describes the actual situation at the beginning of 1999 with regard to identification and priority setting for health technology assessment (HTA) on a national level in the Netherlands. For this purpose the literature on HTA published in 1980-1998, mainly national, was thoroughly reviewed. Many policy documents and other reports from the 'grey literature' of identification and priority setting for HTA in the Netherlands were also used. The results show that attempts to identify and set priorities for HTA is a new activity in the Netherlands. The three most important actors in the field are the Health Council, the Council for Health Research and the Health Insurance Council. Methodologies differ depending on the content and scope of each programme. In addition, the methods used are not always transparent and the activities are not co-ordinated. The lack of co-ordination is due to the fact that there is no single organisation that is authorized to identify and set priorities for HTA. Suggestions for improving co-ordination are proposed with the aim of developing a truly national effort in this field, which will enable a more balanced and efficient set of HTA activities.

Cost-effectiveness of composite resins and amalgam in the replacement of amalgam Class II restorations.

OBJECTIVES: The replacement of an old amalgam Class II restoration is a common treatment and will remain so for decades. In addition to effectiveness, possible adverse health effects and esthetics, the costs of the treatment options will play a role in the choice of material. The aim of this study was to yield information on the relative cost-effectiveness of the use of composite resins and amalgam for the rerestoration of amalgam Class II restorations. METHODS: As part of a larger randomized clinical trial, treatment effectiveness and treatment costs were estimated in 73 composite and amalgam Class II posterior re-restorations. The main treatment outcome was longevity. Secondary outcomes included need of repair and quality of the margin while in situ. Costs were analyzed from the perspective of dentistry, assuming a treatment strategy aimed at offering 'value for money'. From this perspective, differential costs were based on personnel costs as approximated by treatment time. RESULTS: Replacing an amalgam Class II restoration with amalgam is associated with lower costs than replacing with a composite resin. A sensitivity analysis, considering type of composite, increasing proficiency with the material, and time needed for future removal of material, demonstrated that these differences are fairly robust. The materials performed equally well for the first 5 years after placement with respect to longevity. Differences in secondary outcomes were minor and not all in favor of the same material. CONCLUSIONS: It is tentatively concluded that amalgams are more cost-effective than composites for replacing existing Class II amalgam restorations.

Indirect costs of back pain in the Netherlands: a comparison of the human capital method with the friction cost method.

In this study we estimated the indirect costs of back pain in 1991 in The Netherlands on the basis of two approaches: the traditionally used human capital method and the more recently developed friction cost method. The indirect costs of illness were defined as the value of production losses of paid labour and related costs to society due to back pain. The results of this study in 1991 in The Netherlands show that the short-term indirect costs estimated by the human capital method were more than three times as high as the indirect costs estimated by the friction cost method (US$ 4.6 billion vs. USS 1.5 billion, respectively). The lower estimate of indirect costs when using the friction cost method is mainly due to the fact that in this method actual production losses are estimated during a relatively short friction period, which is defined as the period needed to restore the initial production level. In contrast with the human capital method, long-term absenteeism and disability do not induce additional costs when applying the friction cost method. Since the friction cost method takes into account that employees can be replaced, we believe that this method produces a more accurate estimate of indirect costs than the human capital method. Notwithstanding the resulting decrease in indirect costs of back pain, these costs are still impressive, representing 0.28% of the GNP in The Netherlands in 1991. As a consequence, but particularly stimulated by structural changes in the Dutch social security system, policies aimed at reducing indirect costs of back pain, increasingly concentrate on the development and evaluation of interventions early after the onset of disease. This is complemented, on the one hand, by the development of clinical guidelines for the management of back pain in primary care and, on the other hand, by governmental policies aimed at reintegration of chronically ill in the labour force.

Diffusion of laparoscopic technologies in Denmark.

It has been predicted that minimally invasive therapy will have dramatic consequences for the specialty of general surgery, as demonstrated by the diffusion of laparoscopic cholecystectomy. To investigate the determinants of the diffusion in Denmark of five laparoscopic technologies (cholecystectomy, appendicectomy, surgery for colon cancer, surgery for inguinal hernia and fundoplication), questionnaires on seventeen factors' influence on the adoption (stimulating or impeding) were sent to fifty-nine hospitals. Fifty hospitals (85%) responded. Overall, 98% adopted laparoscopic cholecystectomy in Denmark between 1991 and 1995, whereas the remainder of the technologies were adopted by 7-65% of hospitals performing these operations. Large and specialized hospitals were the earliest adopters. The factors, nature of technology (minimally invasive versus conventional), training (appropriate training courses), competition (between specialties and between hospitals) and media attention have stimulated the diffusion, whereas three budget factors (budget for investment, budget for operation and public regulation) usually had an impeding effect. Stimulating factors prevail for all laparoscopic technologies indicating that some guidance of the adoption and use of new health technologies might be necessary. In Denmark, one of the suggested health policies to secure timely guidance is the establishment of an early warning system.

The use of societal criteria in priority setting for health technology assessment in The Netherlands. Initial experiences and future challenges.

Priority setting for the evaluation of health technologies in the Netherlands is exclusively based on the scientific merits of individual research proposals. This process has not resulted in satisfactory allocation of resources. Therefore, societal criteria for setting priorities for health technology assessment have been proposed as an adjunct to scientific criteria. These societal criteria include the burden of disease, uncertainty about the (cost-)effectiveness of the intervention at issue, the potential benefits of the research project, and its potential impact on health care. To realize the full potential of this model for priority setting, a number of methodological issues need to be addressed. Joint efforts of researchers and policy makers in this field are necessary for future progress.

Evaluation and diffusion of excimer laser treatment of myopia in the United States and in The Netherlands.

Excimer laser photorefractive keratectomy (PRK) is an experimental treatment to correct myopia (short-sightedness) that is diffusing into use without convincing evidence of safety and efficacy. It has been claimed that PRK may render conventional methods of correcting myopia, such as wearing glasses or contact lenses, obsolete. Since about 25% of the world's population is myopic, the consequences of this technology in terms of benefits, risks, and costs could be truly enormous. The fee for the procedure in various countries such as the United States, the Netherlands, and Australia varies from about US $1500 to US $2250 per eye. In the United States, the Food and Drug Administration, acting as authorized in the Medical Devices Act of 1976, has limited the use of PRK to patients participating in clinical trials. In the Netherlands, in contrast, where medical equipment is not regulated, the method has diffused without controls, although it is not reimbursed by health insurance agencies. The procedure has become controversial in the Netherlands because it is provided privately and has been aggressively and inappropriately promoted. The case illustrates the limitations of health policy concerning technologies provided privately and raises a number of social and political questions.

Strategies for successful evaluation and policy-making toward health care technology on the move: the case of medical lasers.

Evaluating new health care technology that is rapidly diffusing is one of the greatest challenges to researchers and policy-makers. If no evaluation is done until the technology is mature, evaluation will not influence processes of diffusion. If evaluation is done early, it may be irrelevant when it is completed, because of developments in the technology and changing indications for its use. Nonetheless, early evaluation seems to be the only strategy possible to improve the integration of evaluation and diffusion. These difficulties are illustrated by the case of lasers. Lasers are diffusing relatively rapidly into health care, and yet few laser applications have been well-evaluated. Looking back over the past 20 years or so, only one public body, the National Eye Institute of the U.S. National Institutes of Health (NIH) seems to have tried to address the problem of laser evaluation. In the case of the Eye Institute, it has consistently identified new technologies for treatment of eye conditions and has mounted well-designed prospective evaluations aimed at influencing clinical practice. However, these evaluations have not been integrated with public policy-making, and therefore their influence has been relatively slow to develop. In recent years, concerns about technology have brought more active attempts to develop public policies to affect diffusion. Excimer laser treatment of coronary artery disease, especially as dealt with in the Netherlands, illustrates how a strategy can be developed. Regulation has allowed diffusion to be constrained while evaluation is carried out. Results of the evaluation will guide subsequent diffusion. In the future, such results will probably be used in determining if the laser treatment should be included in the benefit package of health insurance. A strategy for improving diffusion processes requires continuous monitoring of technological developments in health care to identify candidates for such early assessment. Since assessment resources are limited, setting priorities between candidates for assessment is necessary. Once priorities have been determined, an evaluative strategy can be formulated. As in the case of laser treatment of coronary disease, a mechanism for constraining diffusion until evaluations are completed is necessary. Once the studies are completed, policy-making must be done promptly. The problem of successful implementation of this strategy lies with the public bodies, which are often not prepared to develop an integrated strategy of diffusion based on technology assessment and economic appraisal. Developing such a strategy, which would involve slowing diffusion in some cases and speeding it up in others, seems to have clear benefits.(ABSTRACT TRUNCATED AT 400 WORDS)

Evaluation of argon laser treatment of diabetic retinopathy and its diffusion in The Netherlands.

Argon laser treatment of diabetic retinopathy (DR) is the best evaluated case in the field of minimally invasive therapy. A well-organized randomized controlled trial was followed by formal cost-analyses and cost-effectiveness analyses. Laser treatment of DR proved to be cost-effective in a situation where there was no satisfactory treatment previously. Subsequently, screening strategies for retinopathy were developed. Systematic screening for DR in diabetic populations would be cost-saving from a societal perspective. The availability of effective and cost-effective therapy and cost-saving screening strategies for DR warrants active policy making to stimulate the implementation of strategies to control retinopathy in diabetic populations. Such strategies would ideally include both guided diffusion of argon lasers and the organization of screening programs. Data from the Netherlands are used to illustrate the diffusion of argon lasers in health care. After a slow start, argon lasers have diffused widely in the Dutch health care system. This development is complemented by recommendations for screening of the European diabetic population, which were issued in 1991. More active cooperation of all parties involved would benefit in preventing blindness from DR.

Diffusion of minimally invasive therapy in Europe.

This paper considers the diffusion of the 10 cases presented in this issue. Most of the cases have diffused relatively slowly. This slow diffusion can be explained by a number of factors, including budgetary restraints, financial incentives, physician conservatism, and lack of appropriate training. A consistent thread in the cases is the argument that evidence of effectiveness is not convincing. The article considers whether further diffusion of each innovation can be justified from existing evidence. This information is important for policy purposes. Policies might be developed to encourage or to discourage any potentially important innovation.

Diffusion of minimally invasive therapy in The Netherlands.

In the context of the European project, the diffusion of 10 selected cases of minimally invasive therapy (MIT) in the Dutch health care system was documented and analyzed. In each case the diffusion pattern resulting from the balance of stimulating and impeding factors is described, and summarized in a matrix framework. Budgetary pressures, lack of evidence on effectiveness and physician conservatism are the most important factors impeding diffusion of MIT. Patient demand, media reporting and presence of medical innovators are important diffusion-stimulating factors. Finally, a judgment is made on the policy implications of these findings, based on a comparison of the extent and speed of the diffusion of each case, the quality of evidence on effectiveness and cost-effectiveness and, in a few cases, existing policies. In most cases, more active policy making, either stimulating or otherwise guiding diffusion, would be desirable.