[Benefit assessment of medical devices]. / Nutzenbewertung von Medizinprodukten.

Medical devices play an important role in both the diagnostic and therapeutic care of patients. The hope is that particularly innovative medical devices can contribute to the improvement of patient care. However, there is no mandatory need to conduct clinical studies with medical devices that allow an assessment of their benefit within the framework of EU market access or on the way to reimbursement by the statutory health insurance (SHI) in Germany. Numerous examples show that the existing legal framework for market access and for reimbursement in the SHI system is insufficient for providing patients with only those examination and treatment methods, i. e., medical devices, that comply with the benefit requirement and the imperative for quality stipulated in the Social Code Book V. However, it is possible to conduct meaningful clinical trials, i. e., randomized controlled trials, with medical devices as well. Hence, regular, indication-related benefit assessment of medical devices with a higher risk class as a prerequisite for reimbursement for a specific medical device is not only necessary, but also feasible. The 2014 report of the Advisory Council on the Assessment of Developments in the Healthcare System contains a promising recommendation for implementing this. A regulatory framework as described in the report would allow patients the fastest possible access to safe and effective medical device innovations, while increasing planning reliability for the development and marketing of new products, which has often been criticized as insufficient by manufacturers.

["IGeL" or not: cancer screening always needs comprehensive information]. / IGeL oder Nicht-IGeL : Krebsfrüherkennung braucht immer eine umfassende Aufklärung.

BACKGROUND: Cancer screening tests such as ultrasound scans, extensive skin cancer screening, or the prostate-specific antigen (PSA) test are among the most commonly used individual out-of-pocket health services (in German: Individuelle Gesundheitsleistungen, or IGeL) among people who have statutory health insurance in Germany. They are usually offered as an add-on to the services that are covered by statutory insurers. QUESTIONS AND METHODS: There are a number of reasons why cancer screening tests might not be covered by insurers. The main reasons are because the test does not have any clear benefits, and because the harms outweigh the benefits. This article describes the fundamental difficulties of, and the requirements imposed on, benefit assessments of cancer screening tests. RESULTS: Cancer screening tests that are available as individual out-of-pocket health services are always potentially harmful, while their benefit is either not clear or contested, or there is clearly no benefit. DISCUSSION: Health-care providers who offer cancer screening tests are required to provide interested people with relevant information on the related benefits, harms, and uncertainties of the tests, so as to enable an informed decision. This is especially important when it comes to "IGeL" services.

[Epidemiological methods for health services research]. / Epidemiologische Methoden für die Versorgungsforschung

On July 1, 2009, the German Network for Health Services Research [Deutsches Netzwerk Versorgungsforschung e. V. (DNVF e. V.)] approved the Memorandum III "Methods for Health Services Research", supported by the member societies mentioned as authors and published in this Journal (Gesundheitswesen 2009; 71: 505-510). This is an in-depth publication on the "epidemiological methods for health services research". Legal, political and economic steps of intervention in the medical care system modify the health services structures and processes but the impact of such interventions on the medical care users has, so far and in general, not been examined scientifically. Due to this lack of evaluation, there is, also with regard to the economic situation within the health system, no transparency of potentially severe effects on healthy and, particularly, on ill people. For this very reason, the main questions and focuses of medical care research deal with prevalence, causes and effects of over, under and inappropriate supply of health services, the interaction between diagnostics and therapy, the processes across different sectors and the complex interdependences of health services. This part of the Memorandum of Deutsches Netzwerk für Versorgungsforschung e. V. (DNVF e. V., German Network for Health Services Research) will enumerate the methods and instruments that will be used for planned studies and that have been applied for finished studies of health services research and for the evaluation of its quality and value. Health services research takes advantage of the theories and the methods of the disciplines that are involved in its studies. It does not need a specific research methodology; its methods are adapted to the specific research question. It is rather to be expected that certain issues of this research branch and its access to data will lead to the development of new methods.

[Clinical trials: methodological requirements and interpretation]. / Methodische Anforderungen an klinische Studien und ihre Interpretation.

Clinical trials are performed to answer a large variety of questions. Of special relevance is their use in testing and estimating the benefit of medical interventions. Clinical trials are necessary for drugs, non-drug interventions, prevention and screening as well as diagnostic tests. The fundamentals of clinical trials are very old. Methods have been developed and improved during recent decades. This article describes essentials of modern clinical trial methodology.

[Benefit and benefit assessment]. / Nutzen und Nutzenbewertung.

The term value denotes the effect(s) of an intervention which will improve, by more than just a little, prognosis and/or symptoms and/or quality of life of the patient. The value of a medical intervention has to be assessed in a way that the patient can be adequately informed and believable promises and pronouncements of such an intervention are made. The decisive and only relevant question when assessing value is to what extent the patient profits. The assessment of value is connected with the question about clinically or patient-relevant (i. e. relevant) end points, which for the patient means decisive and perceived events that as a rule have an effect on him/her. It is the aim of value assessment to ensure quality of an individual treatment and of medical practice in a wider sense.

[Post-marketing surveillance studies]. / Klinische Prüfungen nach der Zulassung.

Approval of a drug on the market is typically considered as the successful endpoint of a long development phase. This often leads to reduced interest in further research for the indication approved, while in contrast the patient's as well as physician's interest in further research increases. This paper discusses the main areas of effectiveness, safety and post-marketing practice regarding sensible study types for the specific area and the potential gain of knowledge.

Postprandial blood glucose latency after oatmeal is a valid screening test for diabetic gastropathy in type 1 diabetes, but not in type 2 diabetes.

Disordered gastric motility occurs frequently in diabetes mellitus. Gastric emptying time is abnormal in about 50% of diabetic patients and delayed emptying time is known as an important cause for brittle diabetes in type 1 diabetes. We compared the rise in blood glucose after a standardized meal (oatmeal test) as a noninvasive screening test for diabetic gastropathy with the noninvasive measurement of gastric emptying time with ultrasound in type 1 and type 2 diabetic patients. The test result was considered pathological if the rise of blood glucose after an initial steady state did not reach 20 mg/dl in the first 20 min after the meal (prolonged blood glucose latency). We found a sensitivity of 90% (58.7-99.8) and a specificity of 100% (71.5-100) for the oatmeal test in type 1 diabetes in the gastropathy screening. In type 2 diabetes we found a sensitivity of 13% (1.5-38.3) and a specificity of 78% (60-90.7) (95% CI). In conclusion, the oatmeal test seemed to be a good, noninvasive screening test in diabetic gastropathy in type 1 diabetes, but has no diagnostic value in type 2 diabetes. The causes for such a difference may be due to a different postprandial blood glucose regulation in type 2 diabetes compared to the beta-cell-depleted type 1 diabetes.

[Rapid reviews for evidence-based decision support. (Restricting) requirements]. / Entscheidungsunterstützung durch Kurzstellungnahmen zur Evidenzlage. (Verzicht auf) Anforderungen.

Since evidence-based decision making is increasingly gaining acceptance among German health care authorities the need for evidence-based support for time-critical decisions becomes obvious. The best method to identify and summarize the available evidence is the conduct of systematic reviews of the literature. However, generally systematic reviews are not applicable in matters of urgency, because of their time consuming preparation. Concepts for "rapid reviews" are urgently required which ensure that these reviews still produce reliable results. The article proposes strategies to accelerate the preparation of a systematic review and discusses their possible influences on the conclusions of the review. Research efforts are needed to clarify which of the accelerations actually yield valid results.

[Evidence-based scientific analysis of fundamental Medical Services of Statutory Health Insurance internal principle assessment]. / Die evidenzbasierte wissenschaftliche Analyse als Grundlage MDK-interner Grundsatzgutachten.

In Germany, the increasing relevance of Evidence-based medicine (EbM) is not only a consequence of growing economic limitations in the health care system but of a changed jurisdiction, too: liability of the statutory health insurances (SHI) to pay for medical care depends on the proof of its effectiveness. This is of special importance for the Medical Services in their role as an advisor of the SHI. The article depicts the basic assignments of the Medical Services of the Statutory Health Insurance, their legal frame and the role of EbM in sociomedical expertising. The way of fundamental sociomedical expertising, its internal and external effects, the personnel and technical/logistic requirements are described as well as potential of improvement.

[Evidence-based medicine in the further development of health care systems. Comments on a current discussion]. / Evidenzbasierte Medizin in der Weiterentwicklung des Gesundheitssystems. Anmerkungen zu einer aktuellen Diskussion.

The concept of evidence-based medicine is applicable also in the field of guiding health care systems to overcome deficits in adequate patient care. EbM has already been used in this field and has passed first tests of its practical application. There are some obstacles against the future esteem of EbM. These include some misunderstanding concerning the concept itself, missing routine where external evidence has to be put into practice, and some general resistance. Details are presented and an adequate usage of EbM is argued for.

[How much is "evidence-based"? An overview of the state of the art in research]. / Wie viel ist "evidenzbasiert"? Eine Ubersicht zum aktuellen Forschungsstand.

The proportion of evidence-based health care gives rise to controversy. Estimates range from 4%-20%. Studies trying to ascertain the proportion of evidence-based healthcare show wide variations in the results depending on design, setting, subject, main outcome measures, methodology and definition of evidence from 11-82%. The results should not be generalized to community health care and should not be misused in public discussions.

Intention-to-treat: methods for dealing with missing values in clinical trials of progressively deteriorating diseases.

Since it came up in the 1960s, the principle of intention-to-treat (ITT) has become widely accepted for the analysis of controlled clinical trials. In this context the question of how to perform such an analysis in the presence of missing information about the main endpoint is of major importance. Uncritical use of several ad hoc strategies for dealing with missing values is common in the practice of clinical trials. On the other hand, little is known about possible dangers and problems of applying these strategies. We therefore performed a detailed investigation of different methods for dealing with missing values in order to develop recommendations for their practical use. A simulation study was performed investigating possible consequences on type I error and power of applying different methods for dealing with missing values. The simulations were based on a clinical trial of osteoporosis, a progressively deteriorating disease. The strategies examined can be roughly classified into numerical imputation strategies (last observation carried forward, mean and regression based methods) and non-parametric strategies (rank and dichotomization based methods). Different drop-out mechanisms and different types of progression of disease are considered. The type I error increases drastically for the different strategies, especially if the courses of disease vary between treatment groups. The loss in power can be substantial. There is no strategy which is adequate for all different combinations of drop-out mechanisms, drop-out rates and courses of disease over time. For drop-out rates less than 20 per cent and similar courses of disease in the treatment groups, missing values might be replaced by the mean of the other group, or counted as treatment failures after dichotomization of the endpoint. For larger drop-out rates or less similar courses of disease, no adequate recommendations can be given. Because of the drastic consequences of increasing drop-out rates, it has to be a primary goal in clinical trials to keep missing values to a minimum. Unobserved information cannot be reliably regained by any methodological resources. As there are no strategies for universal use, reasons for the choice of a certain method have to be provided when designing and analysing clinical trials.

[Neurological scales as endpoints in stroke studies. Aspects of statistical evaluation]. / Neurologische Skalen als Endpunkte in Schlaganfallstudien. Aspekte der statistischen Auswertung.

Even after publication of ECASS II, the latest paper in a series of large, placebo-controlled studies on thrombolysis in acute ischaemic stroke, there is still uncertainty as to what the best clinical endpoint(s) is (are) in trial design for reliably identifying significant differences between treatment groups. If the expected treatment difference as measured by a neurological outcome scale like the Modified Rankin Scale corresponds more to a shift in dispersion (on average a majority of patients profits greatly) rather than to a shift in location (on average each patient profits much), then the power of the odds ratio test is much higher than that of the Wilcoxon test and therefore the clinical outcome parameters should be dichotomised. With respect to the time window of 0-6 hrs from symptom onset of an acute ischaemic stroke, for example, a dichotomisation of 0-2 vs. 3-6 for the Modified Rankin Scale is reasonable. In the case of multiple endpoints, a global (multivariate) test should be used, but the correlation between these endpoints must not be too high, which means that the various manifestations of the complex stroke disease should be considered.

[Publications of dissertations on unconventional medical therapy and diagnosis procedures--a contribution to "publication bias"]. / Veröffentlichungen von Dissertationen zu unkonventionellen medizinischen Therapie- und Diagnoseverfahren - ein Beitrag zum <>

BACKGROUND: The problem of the so-called publication bias has received much attention during the last few years. It may be a major threat to the results of meta-analyses and systematic reviews. Its implications are not completely clear, and successful strategies to deal with this problem are far from being established. Some studies have begun to identify characteristic items which de- or increase the likelihood of publication of research results. AIM: It was to be investigated, whether or not a publication bias can be proved for results of medical theses on all kinds of complementary medical subjects and which modifying factors can be identified. METHODS: All 140 medical theses on aspects of complementary medicine of the years 1982-1992 were included. Data were extracted, and publications were searched for in MEDLINE and by personal communication with the authors and supervisors. Factors that may influence the likelihood of publication were identified by means of bivariate analysis and logistic regression analysis. RESULTS: Publications were found for 53 (37,9%) of medical theses included. The most dominant factors which were found to influence the likelihood of publication were 'positive result' (OR 2.337; 95% CI 0.733; 7.450), 'high-level statistical analysis' (1.483; 95% CI 0.710; 3.097), 'supervisers with a high publication output' (1.477; 95% CI 0.164; 13.267), and 'candidates of younger age' (0.691; 95% CI 0.388; 1.230). CONCLUSIONS: As it was found for other medical subjects, an apparent publication bias was shown in complementary medicine, with positive results having a greater chance of publication than negative ones.