The Range and Scientific Value of Randomized Trials.

BACKGROUND: The randomized, controlled trial (RCT) is the gold standard of scientific evidence for the attribution of clinical effects (benefits and harms) to medical interventions. Many different designs for RCTs have been developed in order to counter legitimate critical objections and to better adapt the trials to the continually changing challenges that face clinical research. METHODS: The diversity and adaptability of randomized trial designs are presented and discussed on the basis of a selective literature review and specific illustrative examples. RESULTS: A wide range of RCT designs enables adaptation to special research tasks and clinical framework conditions. These include (among others) crossover trials, n=1 trials, factorial RCT designs, and cluster-randomized trials. In addition, adaptive designs such as modern platform trials and pragmatic RCTs with simplified clinical questions and less severely restricted patient groups make broad recruitment of patients possible even in routine clinical practice. CONCLUSION: Only the randomized allocation of subjects to the treatment and control groups, which is the defining property of RCTs, can adequately ensure that traits of the subjects which might disturb or bias a comparison of two or more medical interventions, will be evenly distributed across groups, regardless of whether these traits are known or unknown. The methodological variants and further elaborations of the RCT that are discussed here will help protect patients by enabling the assessment of the benefits and harms of medical methods and products on the basis of robust evidence even in the present era of rapid innovation.

Evaluation of simparteam - a needs-orientated team training format for obstetrics and neonatology.

INTRODUCTION: A standardized team-training program for healthcare professionals in obstetric units was developed based on an analysis of common causes for adverse events found in claims registries. The interdisciplinary and inter-professional training concept included both technical and non-technical skill training. Evaluation of the program was carried out in hospitals with respect to the immediate personal learning of participants and also regarding changes in safety culture. METHODS: Trainings in n=7 hospitals including n=270 participants was evaluated using questionnaires. These were administered at four points in time to staff from participating obstetric units: (1) 10 days ahead of the training (n=308), (2) on training day before (n=239), (3) right after training (n=248), and (4) 6 months after (n=188) the intervention. Questionnaires included several questions for technical and non-technical skills and the Hospital Survey on Patient Safety (HSOPS). RESULTS: Strong effects were found in the participants' perception of their own competence regarding technical skills and handling of emergencies. Small effects could be observed in the scales of the HSOPS questionnaire. Most effects differed depending on professional groups and hospitals. CONCLUSIONS: Integrated technical and team management training can raise employees' confidence with complex emergency management skills and processes. Some indications for improvements on the patient safety culture level were detected. Furthermore, differences between professional groups and hospitals were found, indicating the need for more research on contributing factors for patient safety and for the success of crew resource management (CRM) trainings.

Health technology assessment of medical devices: What is different? An overview of three European projects.

BACKGROUND: With the growing use and importance of health technology assessment (HTA) in decision making during recent years, health technology assessors, decision makers and stakeholders are confronted with methodological challenges due to specific characteristics of health technologies (e. g., pharmaceuticals, diagnostic tests, screening programs), their developmental environment, and their regulation process. Being aware of the necessity to use HTA as a policy instrument for sustainable health care systems in a regulatory environment of decentralized Conformité Européenne (CE) marking, the European Union (EU) is increasingly supporting the development of methods for the assessment of medical devices (MD) on different levels: within the scope of European research projects and within joint assessment activities of the member states of the European network for Health Technology Assessment (EUnetHTA). OBJECTIVE: First, this article describes three projects: MedtecHTA-Methods for Health Technology Assessment of Medical Devices, a European Perspective Work Package 3 (WP3), Comparative Effectiveness of Medical Devices led by the University for Health Sciences, Medical Informatics and Technology (UMIT). Second, we discuss the experiences of the Ludwig Boltzmann Institute Health Technology Assessment (LBI HTA) with the joint production of rapid assessments of medical devices by several European HTA agencies within EUnetHTA. Third, a brief outline is given of the framework of joint methodological guideline elaboration by the EUnetHTA partner organizations because a guideline for therapeutic MD is also being developed here. METHODS: We will describe aims, methods and some preliminary results of MedtecHTA and EUnetHTA Joint Action 2 Work Package 5 Strand B (WP5B) applying the HTA Core Model for Rapid Assessment for national adaptation and reporting, and give an overview of the development process of methodological guidelines within WP 7 of EUnetHTA Joint Action 2. RESULTS: Based on a literature review in MedtecHTA WP3 incremental development, context dependency and the physical mode of action of MD were identified as those characteristics making therapeutic MD different from drugs with regard to evaluation methods. In addition, regulation does not stipulate clinical trials. These characteristics were also identified as challenges for the production of joint assessments of MD within the HTA network EUnetHTA. Furthermore, adequate timing of assessment production, the variety of involved manufacturers, the non-transparent regulation process of MD in Europe and the often poor evidence base pose a challenge to EUnetHTA assessors. As a consequence, processes and methods for the joint production of rapid assessments must be continuously adapted and improved. DISCUSSION: Research on HTA methods for the assessment of MD tries to provide tools to deal with rapidly developing devices during evidence generation, dependence of clinical effectiveness of MD on user experience and context factors. There are also tools to integrate evidence from different sources adjusting for different levels of validity, but these methods are not established and need high epidemiological and statistical expertise. A framework for deciding whether additional evidence is needed to reduce uncertainty regarding safety, clinical effectiveness and cost-effectiveness will be adapted to MD. The whole process of evidence generation before and after market access has to be considered to provide an environment for conclusive HTA recommendations informing health care decision making. In Joint Action 2, EUnetHTA develops transparent processes for the early dialogue with stakeholders and fosters dissemination of appropriate HTA methods. In the case of MD, there are special accumulated needs for such efforts.

[Review: Patient safety as a national health goal: current state and essential fields of action for the German healthcare system]. / Übersichtsartikel: Patientensicherheit als nationales Gesundheitsziel: Status und notwendige Handlungsfelder für die Gesundheitsversorgung in Deutschland.

For some years patient safety has been an important topic for the design of the healthcare systems in many countries. In Germany we are still in the starting phase of this development. Here, patient safety is not a main focus for research and there is only little funding for these topics. Thus most findings on patient safety have been derived in foreign studies. Slowly, some find their way into the clinical routine in Germany. This paper summarises the state of development of patient safety from a trans-sectoral point of view and outlines essential fields of action for the German healthcare system.

Dementia care in the general practice setting: a cluster randomized trial on the effectiveness and cost impact of three management strategies.

OBJECTIVE: To compare a complex nondrug intervention including actively approaching counseling and caregiver support groups with differing intensity against usual care with respect to time to institutionalization in patients with dementia. METHODS: Within this three-armed cluster-randomized controlled trial, 390 community-dwelling patients aged 65 years or older with physician-diagnosed mild to moderate dementia and their caregivers were enrolled via 129 general practitioners in Middle Franconia, Germany. The intervention included general practitioners' training in dementia care and their recommendation of support groups and actively approaching caregiver counseling. Primary study end point was time to institutionalization over 2 years. In addition, long-term intervention effects were assessed over a time horizon of 4 years. Secondary end points included cognitive functioning, (instrumental) activities of daily living, burden of caregiving, and health-related quality of life after 2 years. Frailty models with strict intention-to-treat approach and mixed linear models were applied to account for cluster randomization. Health care costs were assessed from the societal perspective. RESULTS: After 2 (4) years, 12% (24%) of the patients were institutionalized and another 21% (35%) died before institutionalization. No significant differences between study groups were observed with respect to time to institutionalization after 2 and 4 years (P 0.25 and 0.71, respectively). Secondary end points deteriorated, but differences were not significant between study groups. Almost 80% of the health care costs were due to informal care. Total annual costs amounted to more than €47,000 per patient and did not differ between study arms. CONCLUSION: The intervention showed no effects on time to institutionalization and secondary outcomes.

Regulating open disclosure: a German perspective.

The issue of open disclosure has received growing attention from policy-makers, legal experts and academic researchers, predominantly in a number of English-speaking countries. While implementing open disclosure in practice is still an on-going process, open disclosure now forms an integral part of health policy in various American states, the UK, Canada, Australia and New Zealand, with a number of measures having been put in place to encourage open disclosure and to mitigate some of the barriers to such open communication. In contrast, this issue has received little attention in non-English-speaking countries and there is currently no empirical data relating to actual practice or practitioners' attitudes and views in most countries in continental Europe. This article critically examines Germany's current approach to open disclosure. It finds that the issue plays no significant role in German health policy with very limited measures explicitly concerning such communication currently in place. While a number of aspects of the wider regulatory framework appear to be supportive, Germany is still in the early stages of a systematic approach and additional measures are required to further promote open disclosure within the self-governing German healthcare system. This exploration provides an example of a non-English-speaking country's approach to open disclosure and may be of particular interest to neighbouring German-speaking and civil law countries such as Switzerland and Austria.

Costs of care for dementia patients in community setting: an analysis for mild and moderate disease stage.

OBJECTIVE: Rising life expectancy is associated with higher prevalence rates of dementia disorders. When disease progresses the patients' call on formal health care services and on social support grows which imposes increasing costs of care. The aim of this study was to investigate the costs for patients with mild and moderate dementia in community setting in Germany. METHODS: We assessed total costs of care and individual cost components for 383 community-living dementia patients alongside a cluster-randomized trial from societal and health insurance perspective. Utilization of formal health care services was based on insurance claims data and time dedicated to informal care was assessed within caregiver interviews. We estimated costs using a two-part regression model adjusting for age, gender and cluster-effects. RESULTS: Costs of care equal €47,747 (Euros) from societal perspective which is almost the 4.7-fold of health insurance expenditures. Valued informal care covers 80.2% of societal costs and increases disproportionally when disease progresses. In moderate dementia the corresponding amount exceeds the one in mild dementia by 69.9%, whereas costs for formal health care services differ by 14.3%. CONCLUSION: Due to valued informal care, costs of care for community-living patients with moderate dementia are significantly higher than for patients with mild dementia. Informal care is a non-cash item saving expenditures for professional care. To relieve social security system and family caregivers as well as to allow dementia patients to stay at home as long as possible, concepts fostering community-based dementia care and support to family caregivers need to be further developed.

Effects of general practitioner training and family support services on the care of home-dwelling dementia patients--results of a controlled cluster-randomized study.

BACKGROUND: More than 90% of dementia patients are cared for by their general practitioners, who are decisively involved in the diagnosis, therapy and recommendation of support services. OBJECTIVE: To test whether special training of general practitioners alters the care of dementia patients through their systematic recommendation of caregiver counseling and support groups. METHOD: 129 general practitioners enrolled 390 dementia patients and their informal caregivers in a prospective, three-arm cluster-randomized 2-year study. Arm A constituted usual care, in Arm B and C support groups and caregiver counseling (in Arm B one year after baseline, in Arm C at baseline) were recommended by the general practitioners. The general practitioners received arm-specific training. Diagnostic and therapeutic behavior of physicians was recorded at baseline. Informal caregivers were questioned in follow-up after 2 years about the utilization of support services. RESULTS: The diagnostic behavior of the general practitioners conforms to relevant guidelines. The procedure in newly-diagnosed patients does not differ from previously diagnosed patients with the exception of the rate of referral to a specialist. About one-third of the newly-diagnosed dementia patients are given an anti-dementia drug. The utilization of support groups and counseling increased five- and fourfold, respectively. Utilization of other support services remained low (< 10%), with the exception of home nursing and institutional short-term nursing. CONCLUSION: Trained general practitioners usually act in conformity with guidelines with respect to diagnosing dementia, and partly in conformity with the guidelines with respect to recommended drug therapy. Recommendations of support services for informal caregivers by the general practitioner are successful. They result in a marked increase in the utilization rate for the recommended services compared to offers which are not recommended by the general practitioner. TRIAL REGISTRATION: ISRCTN68329593.

[Safety culture in the context of work intensification--development in Germany over the last 10 years]. / Sicherheitskultur in verdichteten Arbeitsbedingungen--die Entwicklung in Deutschland in den letzten 10 Jahren.

This article tries to review the development of patient safety culture in the German healthcare system over the last decade. Since the use of standardized questionnaires and other instruments to measure safety culture in Germany has only just begun there are no representative and longitudinal data. Therefore a set of indicators and clues is chosen to characterise the safety culture development on the micro-, meso- and macro-level of the healthcare system in four areas. Is patient safety an issue of the healthcare debates and especially of research? Have dedicated structures and processes been implemented to support clinical risk management? What are the objective outcomes of healthcare and treatment in regard to patient safety? In summary, there are a lot of signs that patient safety issues in Germany are gaining more and more importance on all levels of the healthcare system. To date there have been single evidence-based studies only indicating a causal or close temporal relationship between patient safety outcomes and the increasing efforts of hospitals, outpatient and long-term care facilities.

Dementia care initiative in primary practice: study protocol of a cluster randomized trial on dementia management in a general practice setting.

BACKGROUND: Current guidelines for dementia care recommend the combination of drug therapy with non-pharmaceutical measures like counselling and social support. However, the scientific evidence concerning non-pharmaceutical interventions for dementia patients and their informal caregivers remains inconclusive. Targets of modern comprehensive dementia care are to enable patients to live at home as long and as independent as possible and to reduce the burden of caregivers. The objective of the study is to compare a complex intervention including caregiver support groups and counselling against usual care in terms of time to nursing home placement. In this paper the study protocol is described. METHODS/DESIGN: The IDA (Initiative Demenzversorgung in der Allgemeinmedizin) project is designed as a three armed cluster-randomized trial where dementia patients and their informal caregivers are recruited by general practitioners. Patients in the study region of Middle Franconia, Germany, are included if they have mild or moderate dementia, are at least 65 years old, and are members of the German AOK (Allgemeine Ortskrankenkasse) sickness fund. In the control group patients receive regular treatment, whereas in the two intervention groups general practitioners participate in a training course in evidence based dementia treatment, recommend support groups and offer counseling to the family caregivers either beginning at baseline or after the 1-year follow-up. The study recruitment and follow-up took place from July 2005 to January 2009. 303 general practitioners were randomized of which 129 recruited a total of 390 patients. Time to nursing home admission within the two year intervention and follow-up period is the primary endpoint. Secondary endpoints are cognitive status, activities of daily living, burden of care giving as well as healthcare costs. For an economic analysis from the societal perspective, data are collected from caregivers as well as by the use of routine data from statutory health insurance and long-term care insurance. DISCUSSION: From a public health perspective, the IDA trial is expected to lead to evidence based results on the community effectiveness of non-pharmaceutical support measures for dementia patients and their caregivers in the primary care sector. For health policy makers it is necessary to make their decisions about financing new services based on strong knowledge about the acceptance of measures in the population and their cost-effectiveness. TRIAL REGISTRATION: ISRCTN68329593.

[IDA project--concept and implementation of a cluster-randomized trial on dementia management in a general practice setting]. / Projekt IDA - Konzept und Umsetzung einer cluster-randomisierten Studie zur Demenzver- sorgung im hausärztlichen Bereich.

Given the multiple deficits in dementia care IDA is a health services research project that addresses the key role of general practitioners in the early detection of dementia, patient and family education, therapy and referral to further counseling and supportive measures. Mid 2005 IDA was started by the AOK Bavaria as a pilot project targeting patients living at home. This three-armed cluster-randomized trial--currently including 180 participating general practitioners--is to compare two supportive measures of different intensity (counseling for care-giving relatives and care management) with the usual care in terms of time to nursing home placement. Additional outcomes investigated include the development of the patient's cognitive status and his abilities to perform activities of daily living, burden and quality of life of care-giving relatives as well as healthcare costs and costs of institutional care. Participating patients with initially mild to moderate disease will be observed for a period of two years. Data collection will proceed via general practitioners and caregivers and also utilize routine data of statutory health insurances and long-term care insurances. Keeping in mind that patient recruitment is ongoing throughout 2006 the initial analysis of 254 patients' data shows an average 80-year old patient in the early phase of moderate dementia. One third of the participants are cases with a first- time diagnosis obtained from their general practitioner. Final results for IDA are expected to be available in 2009.

[Multimodal training of general practitioners--evaluation and knowledge increase within the framework of the dementia management initiative in general medicine (IDA)]. / Multimodale Schulung von Hausärzten - Evaluation und Wissenszuwachs im Rahmen der Initiative Demenzversorgung in der Algemeinmedizin (IDA).

BACKGROUND AND OBJECTIVE: In many industrialized countries diagnostic and therapeutic deficits in the management of patients with dementia are well documented. Due to demographic trends the next years will see a further rise in the number of affected patients. Accordingly, the knowledge and competence of the physicians taking care of these patients need to be keep up-to-date. In the context of the three-armed cluster-randomized IDA trial (IDA = "Initiative Demenzversorgung in der Allgemeinmedizin"; Dementia Management Initiative in General Medicine), general practitioners (GPs) from the trial area (Bavaria, Germany) were trained in the diagnosis and treatment of dementia. METHODS: The educational training concept was based on the evidence-based guideline of Witten/Herdecke University (UWH). All participating GPs (n = 137, January 2006) received three hours training in the diagnosis of dementia. In addition, a subgroup was trained for two hours in dementia therapy (n = 90). Both groups obtained information about the study design. The didactic concept included screen and oral presentations by opinion leaders, video and interactive elements. At the beginning of the training sessions participants had to fill in a pilot-tested questionnaire with 20 multiple choice questions addressing the diagnosis and therapy of dementia (pretest). The same questionnaire was completed at the end of the training session (posttest) complemented by an evaluation sheet. Overall and intergroup differences between pre- and post-test results (increase in knowledge) were compared using the Chi-Square test. RESULTS: Overall, the quality of the training received a positive rating by the participants. By the end of January 2006, 137 doctors had been trained. The mean knowledge gain was 4.0+2.6 correctly answered questions (p<0.001; Cl 3.6 to 4.5) comparing pre- and posttest (n = 132). In the group trained on diagnosis alone (n = 45), the gain averaged 2.0+/-1.9 questions. The group with additional training on therapy (n = 87) achieved a difference of 5.1 -2.3 questions (p<0.001). DISCUSSION: Participants of the dementia training achieved a substantial gain of knowledge. The extent of this knowledge increase was associated with the attendance to respective training modules. An ongoing trial will add further information about knowledge translation in the field of dementia.