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Background: Influenza is a worldwide prevalent infectious disease of the respiratory tract annually causing high morbidity and mortality in Germany. Influenza is preventable by vaccination and this vaccination is so far recommended by the The German Standing Committee on Vaccination (STIKO) as a standard vaccination for people from the age of 60 onwards. Up to date a parenterally administered trivalent inactivated vaccine (TIV) has been in use almost exclusively. Since 2011 however a live-attenuated vaccine (LAIV) has been approved additionally. Consecutively, since 2013 the STIKO recommends LAIV (besides TIV) for children from 2 to 17 years of age, within the scope of vaccination by specified indications. LAIV should be preferred administered in children from 2 to 6 of age. The objective of this Health Technology Assessment (HTA) is to address various research issues regarding the vaccination of children with LAIV. The analysis was performed from a medical, epidemiological and health economic perspective, as well as from an ethical, social and legal point of view. Method: An extensive systematic database research was performed to obtain relevant information. In addition a supplementary research by hand was done. Identified literature was screened in two passes by two independent reviewers using predefined inclusion and exclusion criteria. Included literature was evaluated in full-text using acknowledged standards. Studies were graded with the highest level of evidence (1++), if they met the criteria of European Medicines Agency (EMA)-Guidance: Points to consider on applications with 1. meta-analyses; 2. one pivotal study. Results: For the medical section, the age of the study participants ranges from 6 months to 17 years. Regarding study efficacy, in children aged 6 months to ≤7 years, LAIV is superior to placebo as well as to a vac-cination with TIV (Relative Risk Reduction – RRR – of laboratory confirmed influenza infection approx. 80% and 50%, respectively). In children aged >7 to 17 years (= 18th year of their lives), LAIV is superior to a vaccination with TIV (RRR 32%). For this age group, no studies that compared LAIV with placebo were identified. It can be concluded that there is high evidence for superior efficacy of LAIV (compared to placebo or TIV) among children aged 6 months to ≤7 years. For children from >7 to 17 years, there is moderate evidence for superiority of LAIV for children with asthma, while direct evidence for children from the general population is lacking for this age group. Due to the efficacy of LAIV in children aged 6 months to ≤7 years (high evidence) and the efficacy of LAIV in children with asthma aged >7 to 17 years (moderate evidence), LAIV is also very likely to be efficacious among children in the general population aged >7 to 17 years (indirect evidence). In the included studies with children aged 2 to 17 years, LAIV was safe and well-tolerated; while in younger children LAIV may increase the risk of obstruction of the airways (e.g. wheezing). In the majority of the evaluated epidemiological studies, LAIV proved to be effective in the prevention of influenza among children aged 2–17 years under everyday conditions (effectiveness). The trend appears to indicate that LAIV is more effective than TIV, although this can only be based on limited evidence for methodological reasons (observational studies). In addition to a direct protective effect for vaccinated children themselves, indirect protective ("herd protection") effects were reported among non-vaccinated elderly population groups, even at relatively low vaccination coverage of children. With regard to safety, LAIV generally can be considered equivalent to TIV. This also applies to the use among children with mild chronically obstructive conditions, from whom LAIV therefore does not have to be withheld. In all included epidemiological studies, there was some risk of bias identified, e.g. due to residual confounding or other methodology-related sources of error. In the evaluated studies, both the vaccination of children with previous illnesses and the routine vaccination of (healthy) children frequently involve cost savings. This is especially the case if one includes indirect costs from a societal perspective. From a payer perspective, a routine vaccination of children is often regarded as a highly cost-effective intervention. However, not all of the studies arrive at consistent results. In isolated cases, relatively high levels of cost-effectiveness are reported that make it difficult to perform a conclusive assessment from an economic perspective. Based on the included studies, it is not possible to make a clear statement about the budget impact of using LAIV. None of the evaluated studies provides results for the context of the German healthcare setting. The efficacy of the vaccine, physicians' recommendations, and a potential reduction in influenza symptoms appear to play a role in the vaccination decision taken by parents/custodians on behalf of their children. Major barriers to the utilization of influenza vaccination services are a low level of perception and an underestimation of the disease risk, reservations concerning the safety and efficacy of the vaccine, and potential side effects of the vaccine. For some of the parents surveyed, the question as to whether the vaccine is administered as an injection or nasal spray might also be important. Conclusion: In children aged 2 to 17 years, the use of LAIV can lead to a reduction of the number of influenza cases and the associated burden of disease. In addition, indirect preventive effects may be expected, especially among elderly age groups. Currently there are no data available for the German healthcare setting. Long-term direct and indirect effectiveness and safety should be supported by surveillance programs with a broader use of LAIV. Since there is no general model available for the German healthcare setting, statements concerning the cost-effectiveness can be made only with precaution. Beside this there is a need to conduct health eco-nomic studies to show the impact of influenza vaccination for children in Germany. Such studies should be based on a dynamic transmission model. Only these models are able to include the indirect protective effects of vaccination correctly. With regard to ethical, social and legal aspects, physicians should discuss with parents the motivations for vaccinating their children and upcoming barriers in order to achieve broader vaccination coverage. The present HTA provides an extensive basis for further scientific approaches and pending decisions relating to health policy., GMS Health Technology Assessment; 10:Doc03; ISSN 1861-8863

The use of central venous catheters coated with antibiotics can avoid bloodstream infections with intensive care patients. This is the result of a scientific examination which has been published by the DIMDI. Costs could be also saved in this way. However, according to the authors, the underlying studies do not allow absolutely valid statements., GMS Health Technology Assessment; 8:Doc08; ISSN 1861-8863

[english] The use of central venous catheters coated with antibiotics can avoid bloodstream infections with intensive care patients. This is the result of a scientific examination which has been published by the DIMDI. Costs could be also saved in this way. However, according to the authors, the underlying studies do not allow absolutely valid statements.[german] Der Einsatz bestimmter Antibiotika-beschichteter Venenkatheter kann bei Intensivpatienten Blutbahninfektionen vermeiden. So das Ergebnis einer wissenschaftlichen Untersuchung, die das DIMDI veröffentlicht hat. Auch ließen sich damit Kosten einsparen. Allerdings erlauben, laut den Autoren, die zugrunde gelegten Studien keine uneingeschränkt gültigen Aussagen.

Health political and scientific background Bone graft substitutes are increasingly being used as supplements to standard care or as alternative to bone grafts in the treatment of traumatic fractures. Research questions The efficacy and cost-effectiveness of bone graft substitutes for the treatment of traumatic fractures as well as the ethical, social and legal implications of their use are the main research questions addressed. Methods A systematic literature search was conducted in electronic medical databases (MEDLINE, EMBASE etc.) in December 2009. Randomised controlled trials (RCT), where applicable also containing relevant health economic evaluations and publications addressing the ethical, social and legal aspects of using bone graft substitutes for fracture treatment were included in the analysis. After assessment of study quality the information synthesis of the medical data was performed using metaanalysis, the synthesis of the health economic data was performed descriptively. Results 14 RCT were included in the medical analysis, and two in the heath economic evaluation. No relevant publications on the ethical, social and legal implications of the bone graft substitute use were found. In the RCT on fracture treatment with bone morphogenetic protein-2 (BMP-2) versus standard care without bone grafting (RCT with an elevated high risk of bias) there was a significant difference in favour of BMP-2 for several outcome measures. The RCT of calcium phosphate (CaP) cement and bone marrow-based composite materials versus autogenous bone grafts (RCT with a high risk of bias) revealed significant differences in favour of bone graft substitutes for some outcome measures. Regarding the other bone graft substitutes, almost all comparisons demonstrated no significant difference. The use of BMP-2 in addition to standard care without bone grafting led in the study to increased treatment costs considering all patients with traumatic open fractures. However, cost savings through the additional use of BMP-2 were calculated in a patient subgroup with high-grade open fractures (Gustilo-Anderson grade IIIB). Cost-effectiveness for BMP-2 versus standard care with autologous bone grafts as well as for other bone graft substitutes in fracture treatment has not been determined yet. Discussion Although there were some significant differences in favour of BMP-2, due to the overall poor quality of the studies the evidence can only be interpreted as suggestive for efficacy. In the case of CaP cements and bone marrow-based bone substitute materials, the evidence is only weakly suggestive for efficacy. From an overall economic perspective, the transferability of the results of the health economic evaluations to the current situation in Germany is limited. Conclusions The current evidence is insufficient to evaluate entirely the use of different bone graft substitutes for fracture treatment. From a medical point of view, BMP-2 is a viable alternative for treatment of open fractures of the tibia, especially in cases where bone grafting is not possible. Autologous bone grafting is preferable comparing to the use of OP-1. Possible advantages of CaP cements and composites containing bone marrow over autogenous bone grafting should be taken into account in clinical decision making. The use of the hydroxyapatite material and allograft bone chips compared to autologous bone grafts cannot be recommended. From a health economic perspective, the use of BMP-2 in addition to standard care without bone grafting is recommended as cost-saving in patients with high-grade open fractures (Gustilo-Anderson grade IIIB). Based on the current evidence no further recommendations can be made regarding the use of bone graft substitutes for the treatment of fractures. To avoid legal implications, use of bone graft substitutes outside their approved indications should be avoided.

[english] Often geriatric patients with secondary diagnosis dementia do not receive a rehabilitation treatment, although it is an obligatory service offered by the statutory health insurance. Scientists have examined the benefit of relevant measures for patients who are slightly or moderately affected with dementia. Thus, also these patients would profit by a rehabilitation.[german] Geriatrische Patienten mit Nebendiagnose Demenz erhalten oft keine Rehabilitation, obwohl diese zu den Pflichtleistungen der gesetzlichen Krankenkasse gehört. Wissenschaftler haben untersucht, ob und wenn ja, welchen Nutzen entsprechende Maßnahmen für leicht bis moderat demenzkranke Patienten haben. Demnach profitieren durchaus auch diese Patienten von einer Rehabilitation.

Health political and scientific background Bone graft substitutes are increasingly being used as supplements to standard care or as alternative to bone grafts in the treatment of traumatic fractures. Research questions The efficacy and cost-effectiveness of bone graft substitutes for the treatment of traumatic fractures as well as the ethical, social and legal implications of their use are the main research questions addressed. Methods A systematic literature search was conducted in electronic medical databases (MEDLINE, EMBASE etc.) in December 2009. Randomised controlled trials (RCT), where applicable also containing relevant health economic evaluations and publications addressing the ethical, social and legal aspects of using bone graft substitutes for fracture treatment were included in the analysis. After assessment of study quality the information synthesis of the medical data was performed using metaanalysis, the synthesis of the health economic data was performed descriptively. Results 14 RCT were included in the medical analysis, and two in the heath economic evaluation. No relevant publications on the ethical, social and legal implications of the bone graft substitute use were found. In the RCT on fracture treatment with bone morphogenetic protein-2 (BMP-2) versus standard care without bone grafting (RCT with an elevated high risk of bias) there was a significant difference in favour of BMP-2 for several outcome measures. The RCT of calcium phosphate (CaP) cement and bone marrow-based composite materials versus autogenous bone grafts (RCT with a high risk of bias) revealed significant differences in favour of bone graft substitutes for some outcome measures. Regarding the other bone graft substitutes, almost all comparisons demonstrated no significant difference.The use of BMP-2 in addition to standard care without bone grafting led in the study to increased treatment costs considering all patients with traumatic open fractures. However, cost savings through the additional use of BMP-2 were calculated in a patient subgroup with high-grade open fractures (Gustilo-Anderson grade IIIB). Cost-effectiveness for BMP-2 versus standard care with autologous bone grafts as well as for other bone graft substitutes in fracture treatment has not been determined yet. Discussion Although there were some significant differences in favour of BMP-2, due to the overall poor quality of the studies the evidence can only be interpreted as suggestive for efficacy. In the case of CaP cements and bone marrow-based bone substitute materials, the evidence is only weakly suggestive for efficacy. From an overall economic perspective, the transferability of the results of the health economic evaluations to the current situation in Germany is limited. Conclusions The current evidence is insufficient to evaluate entirely the use of different bone graft substitutes for fracture treatment. From a medical point of view, BMP-2 is a viable alternative for treatment of open fractures of the tibia, especially in cases where bone grafting is not possible. Autologous bone grafting is preferable comparing to the use of OP-1. Possible advantages of CaP cements and composites containing bone marrow over autogenous bone grafting should be taken into account in clinical decision making. The use of the hydroxyapatite material and allograft bone chips compared to autologous bone grafts cannot be recommended. From a health economic perspective, the use of BMP-2 in addition to standard care without bone grafting is recommended as cost-saving in patients with high-grade open fractures (Gustilo-Anderson grade IIIB). Based on the current evidence no further recommendations can be made regarding the use of bone graft substitutes for the treatment of fractures. To avoid legal implications, use of bone graft substitutes outside their approved indications should be avoided. Gesundheitspolitischer und wissenschaftlicher Hintergrund Bei der Behandlung von traumatischen Frakturen werden zusätzlich zur Standardtherapie und ggf. alternativ zu Knochentransplantaten zunehmend verschiedene Knochenersatzmaterialien eingesetzt. Fragestellung Es stellt sich die Frage nach der Wirksamkeit, Kostenwirksamkeit sowie nach ethischen, sozialen und juristischen Implikationen beim Einsatz von Knochenersatzmaterialien bei traumatischen Frakturen. Methodik Eine systematische Literaturrecherche wird in den medizinischen elektronischen Datenbanken MEDLINE, EMBASE etc. im Dezember 2009 durchgeführt. In die Bewertung werden randomisierte kontrollierte Studien (RCT) ggf. mit gesundheitsökonomischen Analysen sowie Publikationen zu ethischen, sozialen sowie juristischen Aspekten einbezogen. Die medizinische Informationssynthese erfolgt nach Bewertung der Studienqualität u.a. in Form von Metaanalysen, die gesundheitsökonomische Informationssynthese deskriptiv. Ergebnisse 14 RCT werden in die medizinische und zwei Analysen in die gesundheitsökonomische Bewertung einbezogen, zu ethischen, sozialen und juristischen Aspekten werden keine Publikationen identifiziert. Beim Vergleich Bone morphogenetic protein (BMP)-2 gegenüber Standardtherapie ohne Knochentransplantat bei Frakturen ergeben sich in einem RCT (mit erhöhtem Verzerrungspotenzial) signifikante Unterschiede zugunsten BMP-2 bezüglich mehrerer Endpunkte. Bei Calciumphosphat (CaP)-Zementen und knochenmarkhaltigen Kompositmaterialien zeigen sich beim Vergleich gegenüber Knochentransplantaten in den RCT (alle mit hohem Verzerrungspotenzial) signifikante Unterschiede zugunsten der Knochenersatzmaterialien bezüglich einzelner Endpunkte. Bei allen anderen Materialien finden sich in fast allen Vergleichen keine signifikanten Unterschiede.Die BMP-2-Anwendung zusätzlich zur Standardbehandlung ohne Knochentransplantation führt bei Betrachtung aller Patienten mit traumatischen offenen Frakturen zur Kostenerhöhung. Einsparungen durch zusätzlichen BMP-2-Einsatz lassen sich allerdings bei der Patientensubgruppe mit hochgradig offenen Frakturen (Gustilo-Anderson-Grad-IIIB) errechnen. Die Kostenwirksamkeit beim BMP-2-Einsatz vs. Standardbehandlung mit Knochentransplantation sowie beim Einsatz anderer Knochenersatzmaterialien ist bisher nicht ermittelt. Diskussion Aufgrund der schlechten Studienqualität kann trotz einiger signifikanter Unterschiede zugunsten BMP-2 nur von einigen starken Hinweisen, bei CaP-Zementen und knochenmarkhaltigen Knochenersatzmaterialien nur von wenigen schwachen Hinweisen auf eine Wirksamkeit ausgegangen werden. Die Ergebnisübertragbarkeit aus den bewerteten gesundheitsökonomischen Analysen auf die heutige Situation in Deutschland mit gesamtwirtschaftlicher Perspektive ist eingeschränkt. Schlussfolgerungen Die Evidenzlage zum Einsatz von Knochenersatzmaterialien ist unbefriedigend. Aus medizinischer Sicht ist der Einsatz von BMP-2 bei Patienten mit offenen Tibiafrakturen eine Therapieoption, insbesondere wenn keine Knochentransplantation infrage kommt. Dem Einsatz von Osteogenic protein (OP)-1 ist die Knochentransplantation vorzuziehen. Mögliche Vorteile beim Einsatz von CaP-Zementen und knochenmarkhaltigen Kompositmaterialien gegenüber einer Knochentransplantation sollen in die klinische Entscheidungsfindung einbezogen werden. Der Einsatz des Hydroxylapatitmaterials und der Allograft-Knochenchips kann gegenüber einer Knochentransplantation nicht empfohlen werden.Aus gesundheitsökonomischer Sicht ist der Einsatz von BMP-2 zusätzlich zur Standardbehandlung ohne Knochentransplantation nur bei Patienten mit hochgradig offenen Frakturen (Gustilo-Anderson-Grad-IIIB) als kostensparend zu empfehlen. Es können keine weiteren Empfehlungen zum Einsatz von Knochenersatzmaterialien bei Patienten mit Frakturen oder Nonunions gemacht werden. Zur Vermeidung von juristischen Implikationen soll der Einsatz von Knochenersatzmaterialien außerhalb der zugelassenen Indikationen vermieden werden.

[english] The prevalence, diagnostics and therapy of the burnout syndrome are increasingly discussed in the public. The unclear definition and diagnics of the burnout syndrome are scientifically criticized. There are several therapies with unclear evidence for the treatment of burnout in existence.The health technology assessment (HTA) report deals with the question of usage and efficacy of different burnout therapies.For the years 2006 to 2011, a systematic literature research was done in 31 electronic databases (e.g. EMBASE, MEDLINE, PsycINFO). Important inclusion criteria are burnout, therapeutic intervention and treatment outcome.17 studies meet the inclusion criteria and are regarded for the HTA report. The studies are very heterogeneous (sample size, type of intervention, measuring method, level of evidence). Due to their study design (e.g. four reviews, eight randomized controlled trials) the studies have a comparable high evidence: three times 1A, five times 1B, one time 2A, two times 2B and six times 4. 13 of the 17 studies are dealing with the efficacy of psychotherapy and psychosocial interventions for the reduction of burnout (partly in combination with other techniques). Cognitive behaviour therapy leads to the improvement of emotional exhaustion in the majority of the studies. The evidence is inconsistent for the efficacy of stress management and music therapy. Two studies regarding the efficacy of Qigong therapy do not deliver a distinct result. One study proves the efficacy of roots of Rhodiola rosea (evidence level 1B). Physical therapy is only in one study separately examined and does not show a better result than standard therapy.Despite the number of studies with high evidence the results for the efficacy of burnout therapies are preliminary and do have only limited reach. The authors of the studies complain about the low number of skilled studies for the therapy of burnout. Furthermore, they point to the insufficient evaluation of the therapy studies and the need for further research. Some authors report the effects of considerable natural recovering.Numerous limitations affect the quality of the results. Intervention contents and duration, study design and study size are very diverse and do not permit direct comparison. Most of the samples are small by size with low statistical power, long-term follow-ups are missing. Comorbidities and parallel utilized therapies are insufficient documented or controlled. Most of the studies use the Maslach Burnout Inventory (MBI) as diagnostic or outcome-tool, but with different cut-off-points. It should be noticed that the validity of the MBI as diagnostic tool is not proved. Ethical, juridical and social determining factors are not covered or discussed in the studies.The efficacy of therapies for the treatment of the burnout syndrome is insufficient investigated. Only for cognitive behavioural therapy (CBT) exists an adequate number of studies which prove its efficacy. Big long-term experimental studies are missing which compare the efficacy of the single therapies and evaluate their evidence. The natural recovering without any therapy needs further research. Additionally, it has to be examined to what extent therapies and their possible effects are thwarted by the conditions of the working place and the working conditions.[german] Die Prävalenz, Diagnostik und Therapie des Burnout-Syndroms wird in der (Fach)Öffentlichkeit zunehmend diskutiert. Wissenschaftlich wird die unklare Definition und Diagnostik des Burnout-Syndroms kritisiert. Zur Behandlung des Burnout werden verschiedene Therapien mit unklarer Evidenz angeboten.Der Health Technology Assessment (HTA)-Bericht befasst sich mit der Frage, welche Therapien zur Behandlung des Burnout-Syndroms eingesetzt werden und wie wirksam diese sind. Die relevante Studienliteratur ist anhand von Schlagworten in 31 Datenbanken (u.a. EMBASE, MEDLINE, PsycINFO) für den Zeitraum 2006 bis 2011 gesucht worden. Wichtige Einschlusskriterien sind Burnout, therapeutische Intervention und Treatment outcome.17 Studien erfüllen die Einschlusskriterien und werden für den HTA-Bericht berücksichtigt. Die Studien sind sehr heterogen (Fallzahl, Stichprobe, Intervention, Messverfahren, Evidenzlevel). Sie haben aufgrund ihres Studiendesigns (u.a. vier Reviews, acht randomisierte kontrollierte Studien) eine vergleichsweise hohe Evidenz: dreimal 1A, fünfmal 1B, einmal 2A, zweimal 2B und sechsmal 4. 13 der 17 Studien befassen sich mit der Wirkung von Psychotherapie und psychosozialen Interventionen (teilweise in Kombination mit anderen Techniken) Reduktion von Burnout. Der Einsatz kognitiver Verhaltenstherapie (KVT) führt in der Mehrheit der Studien zu Verbesserungen der emotionalen Erschöpfung. Die Evidenz der Wirkung von Stressmanagementtraining auf die Reduktion des Burnout ist ebenso wie die Wirkung von Musiktherapie uneinheitlich. Zwei Studien zur Wirksamkeit der Qigong-Therapie kommen zu keinem eindeutigen Ergebnis. Durch eine Studie mit dem Evidenzgrad 1B wird die Wirksamkeit von Rhodiola rosea (Rosenwurz) belegt. Physiotherapie wird nur in einer Studie isoliert untersucht und ist dort der Standardtherapie nicht überlegen. Trotz einer Reihe von Studien mit hohen Evidenzleveln haben die Aussagen zur Wirksamkeit von Burnout-Therapien vorläufigen Charakter und sind von begrenzter Reichweite. Die Autoren der Studien beklagen die zu geringe Anzahl qualifizierter Studien zur Therapie des Burnout-Syndroms und weisen auf die unzureichende Evaluation von Therapiestudien sowie auf die Notwendigkeit weiterer Forschung hin. Einige Autoren berichten beträchtliche Effekte natürlicher Erholung.Zahlreiche Einschränkungen beeinträchtigen die Qualität der Ergebnisse. Interventionsinhalte und -dauer, Studiendesign und Untersuchungspopulationen sind sehr unterschiedlich und lassen direkte Vergleiche nicht zu. Die Stichproben sind überwiegend klein mit geringer statistischer Power, es fehlen längerfristige Follow-up. Komorbiditäten und parallel in Anspruch genommene Therapien sind unzureichend erfasst bzw. kontrolliert worden. Die weit überwiegende Anzahl der Studien verwendet das Maslach Burnout Inventar, dessen klinische Validität nicht bewiesen ist, als Diagnose- und/oder Outcome-Tool, mit jeweils verschiedenen Cut-off-Werten, zur Bestimmung des (schweren) Burnout. Ethische, soziale und rechtliche Rahmenbedingungen werden in den Studien nicht behandelt.Die Wirkung der Therapien, die zur Behandlung des Burnout-Syndroms eingesetzt werden, ist unzureichend erforscht. Es liegt nur zur Wirkung der KVT eine hinreichend große Anzahl von Studien vor, die die Wirksamkeit der KVT belegen. Es fehlen große langfristig angelegte experimentelle Studien, die die einzelnen Therapien in ihrer Wirkung vergleichen und evidenzbasiert evaluieren. Auch die ohne Einfluss einer bestimmten Therapie erreichte „natürliche“ Erholung ist näher zu untersuchen. Es ist außerdem zu prüfen, inwieweit Therapien und ihre mögliche Wirkung durch die Bedingungen am Arbeitsplatz und die Arbeitsplatzsituation konterkariert werden.

[english] Bone graft substitutes are increasingly being used as supplements to standard care or as alternative to bone grafts in the treatment of traumatic fractures.The efficacy and cost-effectiveness of bone graft substitutes for the treatment of traumatic fractures as well as the ethical, social and legal implications of their use are the main research questions addressed.A systematic literature search was conducted in electronic medical databases (MEDLINE, EMBASE etc.) in December 2009. Randomised controlled trials (RCT), where applicable also containing relevant health economic evaluations and publications addressing the ethical, social and legal aspects of using bone graft substitutes for fracture treatment were included in the analysis. After assessment of study quality the information synthesis of the medical data was performed using metaanalysis, the synthesis of the health economic data was performed descriptively. 14 RCT were included in the medical analysis, and two in the heath economic evaluation. No relevant publications on the ethical, social and legal implications of the bone graft substitute use were found. In the RCT on fracture treatment with bone morphogenetic protein-2 (BMP-2) versus standard care without bone grafting (RCT with an elevd high risk of bias) there was a significant difference in favour of BMP-2 for several outcome measures. The RCT of calcium phosphate (CaP) cement and bone marrow-based composite materials versus autogenous bone grafts (RCT with a high risk of bias) revealed significant differences in favour of bone graft substitutes for some outcome measures. Regarding the other bone graft substitutes, almost all comparisons demonstrated no significant difference.The use of BMP-2 in addition to standard care without bone grafting led in the study to increased treatment costs considering all patients with traumatic open fractures. However, cost savings through the additional use of BMP-2 were calculated in a patient subgroup with high-grade open fractures (Gustilo-Anderson grade IIIB). Cost-effectiveness for BMP-2 versus standard care with autologous bone grafts as well as for other bone graft substitutes in fracture treatment has not been determined yet. Although there were some significant differences in favour of BMP-2, due to the overall poor quality of the studies the evidence can only be interpreted as suggestive for efficacy. In the case of CaP cements and bone marrow-based bone substitute materials, the evidence is only weakly suggestive for efficacy. From an overall economic perspective, the transferability of the results of the health economic evaluations to the current situation in Germany is limited.The current evidence is insufficient to evaluate entirely the use of different bone graft substitutes for fracture treatment. From a medical point of view, BMP-2 is a viable alternative for treatment of open fractures of the tibia, especially in cases where bone grafting is not possible. Autologous bone grafting is preferable comparing to the use of OP-1. Possible advantages of CaP cements and composites containing bone marrow over autogenous bone grafting should be taken into account in clinical decision making. The use of the hydroxyapatite material and allograft bone chips compared to autologous bone grafts cannot be recommended. From a health economic perspective, the use of BMP-2 in addition to standard care without bone grafting is recommended as cost-saving in patients with high-grade open fractures (Gustilo-Anderson grade IIIB). Based on the current evidence no further recommendations can be made regarding the use of bone graft substitutes for the treatment of fractures. To avoid legal implications, use of bone graft substitutes outside their approved indications should be avoided.[german] Bei der Behandlung von traumatischen Frakturen werden zusätzlich zur Standardtherapie und ggf. alternativ zu Knochentransplantaten zunehmend verschiedene Knochenersatzmaterialien eingesetzt.Es stellt sich die Frage nach der Wirksamkeit, Kostenwirksamkeit sowie nach ethischen, sozialen und juristischen Implikationen beim Einsatz von Knochenersatzmaterialien bei traumatischen Frakturen.Eine systematische Literaturrecherche wird in den medizinischen elektronischen Datenbanken MEDLINE, EMBASE etc. im Dezember 2009 durchgeführt. In die Bewertung werden randomisierte kontrollierte Studien (RCT) ggf. mit gesundheitsökonomischen Analysen sowie Publikationen zu ethischen, sozialen sowie juristischen Aspekten einbezogen. Die medizinische Informationssynthese erfolgt nach Bewertung der Studienqualität u.a. in Form von Metaanalysen, die gesundheitsökonomische Informationssynthese deskriptiv.14 RCT werden in die medizinische und zwei Analysen in die gesundheitsökonomische Bewertung einbezogen, zu ethischen, sozialen und juristischen Aspekten werden keine Publikationen identifiziert. Beim Vergleich Bone morphogenetic protein (BMP)-2 gegenüber Standardtherapie ohne Knochentransplantat bei Frakturen ergeben sich in einem RCT (mit erhöhtem Verzerrungspotenzial) signifikante Unterschiede zugunsten BMP-2 bezüglich mehrerer Endpunkte. Bei Calciumphosphat (CaP)-Zementen und knochenmarkhaltigen Kompositmaterialien zeigen sich beim Vergleich gegenüber Knochentransplantaten in den RCT (alle mit hohem Verzerrungspotenzial) signifikante Unterschiede zugunsten der Knochenersatzmaterialien bezüglich einzelner Endpunkte. Bei allen anderen Materialien finden sich in fast allen Vergleichen keine signifikanten Unterschiede.Die BMP-2-Anwendung zusätzlich zur Standardbehandlung ohne Knochentransplantation führt bei Betrachtung aller Patienten mit traumatischen offenen Frakturen zur Kostenerhöhung. Einsparungen durch zusätzlichen BMP-2-Einsatz lassen sich allerdings bei der Patientensubgruppe mit hochgradig offenen Frakturen (Gustilo-Anderson-Grad-IIIB) errechnen. Die Kostenwirksamkeit beim BMP-2-Einsatz vs. Standardbehandlung mit Knochentransplantation sowie beim Einsatz anderer Knochenersatzmaterialien ist bisher nicht ermittelt. Aufgrund der schlechten Studienqualität kann trotz einiger signifikanter Unterschiede zugunsten BMP-2 nur von einigen starken Hinweisen, bei CaP-Zementen und knochenmarkhaltigen Knochenersatzmaterialien nur von wenigen schwachen Hinweisen auf eine Wirksamkeit ausgegangen werden. Die Ergebnisübertragbarkeit aus den bewerteten gesundheitsökonomischen Analysen auf die heutige Situation in Deutschland mit gesamtwirtschaftlicher Perspektive ist eingeschränkt.Die Evidenzlage zum Einsatz von Knochenersatzmaterialien ist unbefriedigend. Aus medizinischer Sicht ist der Einsatz von BMP-2 bei Patienten mit offenen Tibiafrakturen eine Therapieoption, insbesondere wenn keine Knochentransplantation infrage kommt. Dem Einsatz von Osteogenic protein (OP)-1 ist die Knochentransplantation vorzuziehen. Mögliche Vorteile beim Einsatz von CaP-Zementen und knochenmarkhaltigen Kompositmaterialien gegenüber einer Knochentransplantation sollen in die klinische Entscheidungsfindung einbezogen werden. Der Einsatz des Hydroxylapatitmaterials und der Allograft-Knochenchips kann gegenüber einer Knochentransplantation nicht empfohlen werden.Aus gesundheitsökonomischer Sicht ist der Einsatz von BMP-2 zusätzlich zur Standardbehandlung ohne Knochentransplantation nur bei Patienten mit hochgradig offenen Frakturen (Gustilo-Anderson-Grad-IIIB) als kostensparend zu empfehlen. Es können keine weiteren Empfehlungen zum Einsatz von Knochenersatzmaterialien bei Patienten mit Frakturen oder Nonunions gemacht werden. Zur Vermeidung von juristischen Implikationen soll der Einsatz von Knochenersatzmaterialien außerhalb der zugelassenen Indikationen vermieden werden.

[english] Menopause is described as the transition from the reproductive phase of a women to the non reproductive. Changes in hormone levels might lead to complaints and health consequences especially during peri- and postmenopause. Hormone therapy has a potential damaging health risk profile and is recommended for temporal limited therapy for acute vasomotor symptoms only.The present HTA-report aims to assess the effectiveness and the cost-effectiveness of alternative treatment methods for women with postmenopausal symptoms in Germany regarding patient relevant endpoints (reduction of symptoms and frequency of adverse events and improvement of quality of life).A systematic literature search was carried out in 33 relevant databases in September 2010. Citations were selected according to pre-defined criteria and were extracted and evaluated.In the systematic research 22 studies are identified for the effectiveness evaluation, 22 primary studies and one review.High doses of isolated genistein reduce the frequency/intensity of hot flashes while low doses of genistein show no significant effect. Intake of isoflavone extract such as genistein, daidzein, glycitein in various combinations does not have an effect on improvement of cognitive function or vaginal dryness. The effect of black cohosh and hop extract for menopausal complaints cannot be determined since results are heterogenous. The combination of isoflavone, black cohosh, monk’s pepper, valerian and vitamin E has a positive effect on menopause symptoms. Ginkgo biloba shows no significant effect on menopause symptoms and cognitive improvement beside mental flexibility. Acupuncture has a significant influence on hot flashes especially in severe cases.No final statement can be drawn regarding the effectiveness of alter­ne treatment methods due to qualitative shortcomings of included studies and a general limited availability of studies in this field. Furthermore, the generalization of the present HTA is limited due to the inclusion of only postmenopausal women.[german] Als Wechseljahre wird der Übergang von der reproduktiven Phase der Frau zur nicht-reproduktiven beschrieben. Insbesondere in der Peri- und Postmenopause können Beschwerden aufgrund des sich veränderten Hormonspiegels auftreten. Aktuell wird die Hormontherapie wegen der mit dieser verbundenen Risiken nur noch zur kurzfristigen Behandlung akuter vasomotorischer Symptome empfohlen. Von den betroffenen Frauen werden alternative und komplementäre Heilmethoden eingesetzt.Im vorliegenden Health Technology Assessment (HTA) sollen die Effektivität und Kosteneffektivität alternativer Behandlungsmethoden von postmenopausalen Wechseljahresbeschwerden in Deutschland hinsichtlich der patientenrelevanten Endpunkte Verringerung der Symptomatik, Häufigkeit unerwünschter Ereignisse sowie Verbesserung der Lebensqualität bewertet werden. In 33 relevanten Datenbanken wird im September 2010 eine systematische Literatursuche durchgeführt. Gefundene und relevante Literaturstellen werden gemäß vorab definierter Kriterien selektiert. Die Daten der Literaturstellen werden gezielt herausgesucht, bewertet und zusammenfassend beurteilt.Aus der systematischen Recherche werden 22 Studien, davon 15 Primärstudien und ein Review zur Bewertung der Effektivität identifiziert.Hochdosiertes isoliertes Genistein reduziert die Anzahl/Schwere von Hitzewallungen, während niedrig dosiertes Genistein keinen signifikanten Effekt zeigt. Die Gabe von Isoflavonextrakten, die Genistein, Daidzein, Glycitein in unterschiedlicher Zusammensetzung enthalten, hat keinen signifikanten Einfluss auf die Verbesserung kognitiver Fähigkeiten oder vaginale Trockenheit. Traubensilberkerzen- und Hopfenextrakt führen zu unterschiedlichen Ergebnissen bezüglich der Wirksamkeit bei postmenopausalen Beschwerden, sodass keine abschließende Aussage zur Effektivität getroffen werden kann. Die Kombination von Isoflavonen, Traubensilberkerze, Mönchspfeffer, Baldrian und Vitamin E hat eine positive Wirkung auf postmenopausale Symptome. Ginkgo biloba zeigt keinen signifikanten Effekt auf postmenopausale Symptome und eine kognitive Verbesserung mit Ausnahme der mentalen Flexibilität. Akupunktur hat einen signifikanten Einfluss auf Hitzewallungen, insbesondere auf deren Schweregrad.Aufgrund der qualitativen Mängel (Concealment, Randomisierung, Fallzahlplanung) der eingeschlossenen Studien und der begrenzten Anzahl an Studien kann keine abschließende zusammenfassende Bewertung zur Wirksamkeit alternativer Heilmethoden gegeben werden. Die Verallgemeinerbarkeit des vorliegenden HTA wird durch die Beschränkung auf postmenopausale Frauen reduziert.

Scientific background Various diagnostic tests including conventional invasive coronary angiography and non-invasive computed tomography (CT) coronary angiography are used in the diagnosis of coronary heart disease (CHD). Research questions The present report aims to evaluate the clinical efficacy, diagnostic accuracy, prognostic value cost-effectiveness as well as the ethical, social and legal implications of CT coronary angiography versus invasive coronary angiography in the diagnosis of CHD. Methods A systematic literature search was conducted in electronic data bases (MEDLINE, EMBASE etc.) in October 2010 and was completed with a manual search. The literature search was restricted to articles published from 2006 in German or English. Two independent reviewers were involved in the selection of the relevant publications. The medical evaluation was based on systematic reviews of diagnostic studies with invasive coronary angiography as the reference standard and on diagnostic studies with intracoronary pressure measurement as the reference standard. Study results were combined in a meta-analysis with 95 % confidence intervals (CI). Additionally, data on radiation doses from current non-systematic reviews were taken into account. A health economic evaluation was performed by modelling from the social perspective with clinical assumptions derived from the meta-analysis and economic assumptions derived from contemporary German sources. Data on special indications (bypass or in-stent-restenosis) were not included in the evaluation. Only data obtained using CT scanners with at least 64 slices were considered. Results No studies were found regarding the clinical efficacy or prognostic value of CT coronary angiography versus conventional invasive coronary angiography in the diagnosis of CHD. Overall, 15 systematic reviews with data from 44 diagnostic studies using invasive coronary angiography as the reference standard (identification of obstructive stenoses) and two diagnostic studies using intracoronary pressure measurement as the reference standard (identification of functionally relevant stenoses) were included in the medical evaluation. Meta-analysis of the nine studies of higher methodological quality showed that, CT coronary angiography with invasive coronary angiography as the reference standard, had a sensitivity of 96 % (95 % CI: 93 % to 98 %), specificity of 86 % (95 % CI: 83 % to 89 %), positive likelihood ratio of 6.38 (95 % CI: 5.18 to 7.87) and negative likelihood ratio of 0.06 (95 % CI: 0.03 to 0.10). However, due to non-diagnostic CT images approximately 3.6 % of the examined patients required a subsequent invasive coronary angiography. Using intracoronary pressure measurement as the reference standard, CT coronary angiography compared to invasive coronary angiography had a sensitivity of 80 % (95 % CI: 61 % to 92 %) versus 67 % (95 % CI:51 % to 78 %), a specificity of 67 % (95 % CI: 47 % to 83 %) versus 75 % (95 % CI: 60 % to 86 %), an average positive likelihood ratio of 2.3 versus 2.6, and an average negative likelihood ratio 0.3 versus 0.4, respectively. Compared to invasive coronary angiography, the average effective radiation dose of CT coronary angiography was higher with retrospective electrocardiogram (ECG) gating and relatively similar with prospective ECG gating. The health economic model using invasive coronary angiography as the reference standard showed that at a pretest probability of CHD of 50 % or lower, CT coronary angiography resulted in lower cost per patient with true positive diagnosis. At a pretest probability of CHD of 70 % or higher, invasive coronary angiography was associated with lower cost per patient with true positive diagnosis. Using intracoronary pressure measurement as the reference standard, both types of coronary angiographies resulted in substantially higher cost per patient with true positive diagnosis. Two publications dealing explicitly with ethical aspects were identified. The first addressed ethical aspects regarding the principles of beneficence, autonomy and justice, and the second addressed those regarding radiation exposition, especially when used within studies. Discussion The discriminatory power of CT coronary angiography to identify patients with obstructive (above 50 %) coronary stenoses should be regarded as “high diagnostic evidence”, to identify patients without coronary stenoses as “persuasive diagnostic evidence”. The discriminatory power of both types of coronary angiography to identify patients with or without functionally relevant coronary stenoses should be regarded as “weak diagnostic evidence”. It can be assumed that patients with a high pretest probability of CHD will need invasive coronary angiography and patients with a low pretest probability of CHD will not need subsequent revascularisation. Therefore, CT coronary angiography may be used before performing invasive coronary angiography in patients with an intermediate pretest probability of CHD. For identifying or excluding of obstructive coronary stenosis, CT coronary angiography was shown to be more cost-saving at a pretest probability of CHD of 50 % or lower, and invasive coronary angiography at a pretest probability of CHD of 70 % or higher. The use of both types of coronary angiography to identify or to exclude functionally relevant coronary stenoses should be regarded as highly cost-consuming. With regard to ethical, social or legal aspects, the following possible implications were identified: under-provision or over-provision of health care, unnecessary complications, anxiety, social stigmatisation, restriction of self-determination, unequal access to health care, unfair resource distribution and legal disputes. Conclusion From a medical point of view, CT coronary angiography using scanners with at least 64 slices should be recommended as a test to rule out obstructive coronary stenoses in order to avoid inappropriate invasive coronary angiography in patients with an intermediate pretest probability of CHD. From a health economic point of view, this recommendation should be limited to patients with a pretest probability of CHD of 50 % or lower. From a medical and health economic point of view, neither CT coronary angiography using scanners with at least 64 slices nor invasive coronary angiography may be recommended as a single diagnostic test for identifying or ruling out functionally relevant coronary stenoses. To minimise any potential negative ethical, social and legal implications, the general ethical and moral principles of benefit, autonomy and justice should be considered., GMS Health Technology Assessment; 8:Doc02; ISSN 1861-8863

Background An ageing population, a growing prevalence of chronic diseases and limited financial resources for health care underpin the importance of prevention of disabling health disorders and care dependency in the elderly. A wide variety of measures is generally available for the prevention of falls and fall-related injuries. The spectrum ranges from diagnostic procedures for identifying individuals at risk of falling to complex interventions for the removal or reduction of identified risk factors. However, the clinical and economic effectiveness of the majority of recommended strategies for fall prevention is unclear. Against this background, the literature analyses in this HTA report aim to support decision-making for effective and efficient fall prevention. Research questions The pivotal research question addresses the effectiveness of single interventions and complex programmes for the prevention of falls and fall-related injuries. The target population are the elderly (> 60 years), living in their own housing or in long term care facilities. Further research questions refer to the cost-effectiveness of fall prevention measures, and their ethical, social and legal implications. Methods Systematic literature searches were performed in 31 databases covering the publication period from January 2003 to January 2010. While the effectiveness of interventions is solely assessed on the basis of randomised controlled trials (RCT), the assessment of the effectiveness of diagnostic procedures also considers prospective accuracy studies. In order to clarify social, ethical and legal aspects all studies deemed relevant with regard to content were taken into consideration, irrespective of their study design. Study selection and critical appraisal were conducted by two independent assessors. Due to clinical heterogeneity of the studies no meta-analyses were performed. Results Out of 12,000 references retrieved by literature searches, 184 meet the inclusion criteria. However, to a variable degree the validity of their results must be rated as compromised due to different biasing factors. In summary, it appears that the performance of tests or the application of parameters to identify individuals at risk of falling yields little or no clinically relevant information. Positive effects of exercise interventions may be expected in relatively young and healthy seniors, while studies indicate opposite effects in the fragile elderly. For this specific vulnerable population the modification of the housing environment shows protective effects. A low number of studies, low quality of studies or inconsistent results lead to the conclusion that the effectiveness of the following interventions has to be rated unclear yet: correction of vision disorders, modification of psychotropic medication, vitamin D supplementation, nutritional supplements, psychological interventions, education of nursing personnel, multiple and multifactorial programs as well as the application of hip protectors. For the context of the German health care system the economic evaluations of fall prevention retrieved by the literature searches yield very few useful results. Cost-effectiveness calculations of fall prevention are mostly based on weak effectiveness data as well as on epidemiological and cost data from foreign health care systems. Ethical analysis demonstrates ambivalent views of the target population concerning fall risk and the necessity of fall prevention. The willingness to take up preventive measures depends on a variety of personal factors, the quality of information, guidance and decision-making, the prevention program itself and social support. The analysis of papers regarding legal issues shows three main challenges: the uncertainty of which standard of care has to be expected with regard to fall prevention, the necessity to consider the specific conditions of every single case when measures for fall prevention are applied, and the difficulty to balance the rights to autonomous decision making and physical integrity. Discussion and conclusions The assessment of clinical effectiveness of interventions for fall prevention is complicated by inherent methodological problems (esp. absence of blinding) and meaningful clinical heterogeneity of available studies. Therefore meta-analyses are not appropriate, and single study results are difficult to interpret. Both problems also impair the informative value of economic analyses. With this background it has to be stated that current recommendations regarding fall prevention in the elderly are not fully supported by scientific evidence. In particular, for the generation of new recommendations the dependency of probable effects on specific characteristics of the target populations or care settings should be taken into consideration. This also applies to the variable factors influencing the willingness of the target population to take up and pursue preventive measures. In the planning of future studies equal weight should be placed on methodological rigour (freedom from biases) and transferability of results into routine care. Economic analyses require input of German data, either in form of a “piggy back study“ or in form of a modelling study that reflects the structures of the German health care system and is based on German epidemiological and cost data., GMS Health Technology Assessment; 8:Doc01; ISSN 1861-8863

Background The increasing proportion of elderly people with respective care requirements and within the total population stands against aging personnel and staff reduction in the field of health care where employees are exposed to high load factors. Health promotion interventions may be a possibility to improve work situations and behavior. Methods A systematic literature search is conducted in 32 databases limited to English and German publications since 1990. Moreover, internet-searches are performed and the reference lists of identified articles are scanned. The selection of literature was done by two reviewers independently according to inclusion and exclusion criteria. Data extraction and tables of evidence are verified by a second expert just like the assessment of risk of bias by means of the Cochrane Collaboration’s tool. Results We identified eleven intervention studies and two systematic reviews. There were three randomized controlled trials (RCT) and one controlled trial without randomization (CCT) on the improvement of physical health, four RCT and two CCT on the improvement of psychological health and one RCT on both. Study duration ranged from four weeks to two years and the number of participants included from 20 to 345, with a median of 56. Interventions and populations were predominantly heterogeneous. In three studies intervention for the improvement of physical health resulted in less complaints and increased strength and flexibility with statistically significant differences between groups. Regarding psychological health interventions lead to significantly decreased intake of analgesics, better stress management, coping with workload, communication skills and advanced training. Discussion Taking into consideration the small to very small sample sizes, other methodological flaws like a high potential of bias and poor quality of reporting the validity of the results has to be considered as limited. Due to the heterogeneity of health interventions, study populations with differing job specializations and different lengths of study durations and follow-up periods, the comparison of results would not make sense. Conclusions Further research is necessary with larger sample sizes, with a sufficient study duration and follow-up, with a lower risk of bias, by considering of relevant quality criteria and with better reporting in publications., GMS Health Technology Assessment; 7:Doc06; ISSN 1861-8863

Background The German statutory health insurance (GKV) reimburses all health care services that are deemed sufficient, appropriate, and efficient. According to the German Medical Association (BÄK), individual health services (IGeL) are services that are not under liability of the GKV, medically necessary or recommendable or at least justifiable. They have to be explicitly requested by the patient and have to be paid out of pocket. Research questions The following questions regarding IGeL in the outpatient health care of GKV insurants are addressed in the present report: What is the empirical evidence regarding offers, utilization, practice, acceptance, and the relation between physician and patient, as well as the economic relevance of IGeL? What ethical, social, and legal aspects are related to IGeL? For two of the most common IGeL, the screening for glaucoma and the screening for ovarian and endometrial cancer by vaginal ultrasound (VUS), the following questions are addressed: What is the evidence for the clinical effectiveness? Are there sub-populations for whom screening might be beneficial? Methods The evaluation is divided into two parts. For the first part a systematic literature review of primary studies and publications concerning ethical, social and legal aspects is performed. In the second part, rapid assessments of the clinical effectiveness for the two examples, glaucoma and VUS screening, are prepared. Therefore, in a first step, HTA-reports and systematic reviews are searched, followed by a search for original studies published after the end of the research period of the most recent HTA-report included. Results 29 studies were included for the first question. Between 19 and 53% of GKV members receive IGeL offers, of which three-quarters are realised. 16 to 19% of the insurants ask actively for IGeL. Intraocular tension measurement is the most common single IGeL service, accounting for up to 40% of the offers. It is followed by ultrasound assessments with up to 25% of the offers. Cancer screening and blood or laboratory services are also frequent and represent a major proportion of the demand. The ethical, social, and legal aspects discussed in the context of IGeL concern eight subject areas: autonomous patient decisions versus obtrusion, commercialization of medicine, duty of patient information, benefit, evidence, and (quality) control, role and relation of physicians and patients, relation to the GKV, social inequality, formally correct performance. For glaucoma screening, no randomized controlled trial (RCT) is identified that shows a patient relevant benefit. For VUS three RCT are included. However, they do not yet present mortality data concerning screened and non-screened persons. VUS screening shows a high degree of over-diagnosis in turn leading to invasive interventions. To diagnose one invasive carcinoma, 30 to 35 surgical procedures are necessary. Conclusion IGeL are a relevant factor in the German statutory health care system. To provide more transparency, the requests for evidence-based and independent patient information should be considered. Whether official positive and negative-lists could be an appropriate instrument to give guidance to patients and physicians, should be examined. Generally, IGeL must be seen in the broader context of the discussions about the future design and development of the German health care system., GMS Health Technology Assessment; 7:Doc05; ISSN 1861-8863

Introduction and background Invasive home mechanical ventilation is used for patients with chronic respiratory insufficiency. This elaborate and technology-dependent ventilation is carried out via an artificial airway (tracheal cannula) to the trachea. Exact numbers about the incidence of home mechanical ventilation are not available. Patients with neuromuscular diseases represent a large portion of it. Research questions Specific research questions are formulated and answered concerning the dimensions of medicine/nursing, economics, social, ethical and legal aspects. Beyond the technical aspect of the invasive home, mechanical ventilation, medical questions also deal with the patient’s symptoms and clinical signs as well as the frequency of complications. Economic questions pertain to the composition of costs and the differences to other ways of homecare concerning costs and quality of care. Questions regarding social aspects consider the health-related quality of life of patients and caregivers. Additionally, the ethical aspects connected to the decision of home mechanical ventilation are viewed. Finally, legal aspects of financing invasive home mechanical ventilation are discussed. Methods Based on a systematic literature search in 2008 in a total of 31 relevant databases current literature is viewed and selected by means of fixed criteria. Randomized controlled studies, systematic reviews and HTA reports (health technology assessment), clinical studies with patient numbers above ten, health-economic evaluations, primary studies with particular cost analyses and quality-of-life studies related to the research questions are included in the analysis. Results and discussion Invasive mechanical ventilation may improve symptoms of hypoventilation, as the analysis of the literature shows. An increase in life expectancy is likely, but for ethical reasons it is not confirmed by premium-quality studies. Complications (e. g. pneumonia) are rare. Mobile home ventilators are available for the implementation of the ventilation. Their technical performance however, differs regrettably. Studies comparing the economic aspects of ventilation in a hospital to outpatient ventilation, describe home ventilation as a more cost-effective alternative to in-patient care in an intensive care unit, however, more expensive in comparison to a noninvasive (via mask) ventilation. Higher expenses arise due to the necessary equipment and the high expenditure of time for the partial 24-hour care of the affected patients through highly qualified personnel. However, none of the studies applies to the German provisionary conditions. The calculated costs strongly depend on national medical fees and wages of caregivers, which barely allows a transmission of the results. The results of quality-of-life studies are mostly qualitative. The patient’s quality of life using mechanical ventilation is predominantly considered well. Caregivers of ventilated patients report positive as well as negative ratings. Regarding the ethical questions, it was researched which aspects of ventilation implementation will have to be considered. From a legal point of view the financing of home ventilation, especially invasive mechanical ventilation, requiring specialised technical nursing is regulated in the code of social law (Sozialgesetzbuch V). The absorption of costs is distributed to different insurance carriers, who often, due to cost pressures within the health care system, insurance carriers, who consider others and not themselves as responsible. Therefore in practice, the necessity to enforce a claim of cost absorption often arises in order to exercise the basic right of free choice of location. Conclusion Positive effects of the invasive mechanical ventilation (overall survival and symptomatic) are highly probable based on the analysed literature, although with a low level of evidence. An establishment of a home ventilation registry and health care research to ascertain valid data to improve outpatient structures is necessary. Gathering specific German data is needed to adequately depict the national concepts of provision and reimbursement. A differentiation of the cost structure according to the type of chosen outpatient care is currently not possible. There is no existing literature concerning the difference of life quality depending on the chosen outpatient care (homecare, assisted living, or in a nursing home specialised in invasive home ventilation). Further research is required. For a so called participative decision – made by the patient after intense counselling – an early and honest patient education pro respectively contra invasive mechanical ventilation is needed. Besides the long term survival, the quality of life and individual, social and religious aspects have also to be considered., GMS Health Technology Assessment; 6:Doc08; ISSN 1861-8863

Background Despite many activities to prevent risky alcohol consumption among adolescents and young adults there is an increase of alcohol intoxications in the group of ten to twenty year old juveniles. Objectives This report gives an overview about the recent literature as well as the German federal prevention system regarding activities concerning behavioral and policy prevention of risky alcohol consumption among children, adolescents and young adults. Furthermore, effective components of prevention activities are identified and the efficiency and efficacy of ongoing prevention programs is evaluated. Methods A systematic literature review is done in 34 databases using Bool’sche combinations of the key words alcohol, prevention, treatment, children, adolescents and young adults. Results 401 studies were found and 59 studies were selected for the health technology assessment (HTA). Most of the studies are done in USA, nine in Germany. A family strengthening program, personalized computer based intervention at schools, colleges and universities, brief motivational interventions and policy elements like increase of prices and taxes proved effective. Discussion Among the 59 studies there are three meta-analyses, 15 reviews, 17 randomized controlled trials (RCT) and 18 cohort studies. Despite the overall high quality of the study design, many of them have methodological weaknesses (missing randomization, missing or too short follow-ups, not clearly defined measurement parameters). The transferability of US-results to the German context is problematic. Only a few prevention activities reach a sustainable reduction of frequency and/or amount of alcohol consumption. Conclusion The HTA-report shows the need to develop specific and target group focused prevention activities for the German situation. Essential for that is the definition of target goals (reduction of consumption, change of behaviour) as well as the definition and empirical validation of risky alcohol consumption. The efficacy of prevention activities should be proven before they are launched. At present activities for the reduction or prevention of risky alcohol consumption are not sufficiently evaluated in Germany concerning their sustainable efficacy., GMS Health Technology Assessment; 7:Doc04; ISSN 1861-8863

Background The HTA-report (HTA = Health Technology Assessment) deals with the primary prevention of cardiovascular diseases and diabetes mellitus type 2. In 2009 approximately 356,000 people died in Germany due to cardiovascular diseases. According to estimations about 6.3 million people are suffering from diabetes mellitus type 2. The interventions that are subsidized by the public health insurance are mainly focused on sufficient physical activities, healthy nutrition, stress management and the reduction of the consumption of addictive drugs and luxury food. Objectives Which lifestyle-related measures and/or programmes for primary prevention of cardiovascular diseases and of the metabolic syndrome are effective? To what extent will the health status be improved by these offers? To what extent will existing health resources and skills be strengthened by these offers? Are there any differences regarding the effectiveness among the interventions with respect to different settings or subgroups? Which lifestyle-related interventions and/or programmes for primary prevention of cardiovascular diseases and of the metabolic syndrome are sustainable and cost-effective? Which outcome parameters are in the view of the contributors decisive for the evaluation of the effectiveness? In the view of the contributor are there different values between the outcome parameters? In the view of the payers and other actors are there different values between the outcome parameters? Which ethical and juridical factors have to be considered? Which social and/or socio-economic parameters influence the use of the services and effectiveness? Methods A systematic literature research is done in 35 databases. For the period 2005 to 2010, reviews, epidemiological and clinical studies as well as economical evaluations which deal with primary prevention programmes regarding cardiovascular diseases or the metabolic syndrome are included. Results 44 publications meet the inclusion criteria. These studies confirm the effectiveness of the primary prevention programmes. Physical activity programs seem to have a stronger effect than nutrition programmes. Psychological programmes prove as well effectiveness, if they include cognitive behaviour therapy. The identified economical studies indicate that programmes for cardiovascular prevention can be conducted cost-effectively. Interventions that focus on the general population turn out to be particularly cost-effective and sustainable. Discussion There is a wide range of primary preventive effective lifestyle-related interventions with high evidence. The outcomes and results are consistent with the recommendations of the two identified evidence-based guidelines regarding the recommendations on lifestyle and healthy nutrition. Furthermore, the cost-effectiveness of primary prevention services is proven. With regard to the economical studies it is however worth noting that this result is based on very few publications. The transferability has to be critically assessed as the studies mainly originate from the American health system. Conclusion On the whole a comprehensive setting approach with educative, somatic, psychosocial and activity therapeutic components is recommended. The sustainability of a prevention intervention must be ensured from programme to programme. Long-term studies are necessary to make valid statements regarding the sustainable effectiveness: There is an essential deficit in the current practiced evaluation of the use of primary prevention services provided by the health insurance – mainly regarding the comprehensive setting approach – regarding the evidence-based evaluation of the prescribed preventive interventions. With regard to the ethical, social and economical evaluation the research situation is deficient. The situation has to be particularly analyzed for the socially deprived and one has to respond to their specific needs for prevention., GMS Health Technology Assessment; 7:Doc02; ISSN 1861-8863

Introduction Ulcers as a result of diabetes mellitus are a serious problem with an enormous impact on the overall global disease burden due to the increasing prevalence of diabetes. Because of long hospital stays, reh abilitat ion, often required home care and the use of social services diab eti c foot complications are costly. Therapy with growth factors could be an effective and innovative add-on to standard wound care. Research questions What is the benefit of therapies with growth factors alone or in combination with other technologies in the treatment of diabetic foot ulcer a sses sed regarding medical, economical, social, ethical and juridical a spec ts? Methods We systematically searched relevant databases limited to English and German language and publications since 1990. Cost values were adj ust ed to the price level of 2008 and converted into Euro. A review and an assessment of the quality of publications were conducted following approved methodical standards conforming to evidence-based medicine and health economics. Results We identified 25 studies (14 randomized controlled trials (RCT), nine cost-effectiveness analyses, two meta-analyses).The RCT compared an add-on therapy to standard wound care with standard wound care/placebo alone or extracellular wound matrix: in six studies becaplermin, in two rhEGF, in one bFGF, and in five studies the metabolically active skin grafts Dermagraft and Apligraf.The study duration ranged from twelve to 20 weeks and the study population included between 17 to 382 patients, average 130 patients.The treatment with becaplermin, rhEGF and skin implants Dermagraft and Apligraf showed in eight out of 13 studies an advantage concerning complete wound closure and the time to complete wound healing. Evidence for a benefit of treatment with bFGF could not be found. In four out of 14 studies the proportion of adverse events was 30% per study group with no difference between the treatment groups. The methodological quality of the studies was affected by significant def icienci es.The results showed becaplermin being cost-effective whereas no obvious statement can be made regarding Dermagraft and Apligraf because of diverging cost bases and incremental cost-effectiveness ratios. Discussion Differences in standard wound care are complicating the comparison of study results. Taking into consideration the small to very small sample sizes and other methodological flaws with high potential of bias, the validity of the results with regard to effectiveness and cost-effectiveness has to be considered limited. The duration of treatment and follow-up examinations is not long enough to assess the sustainability of the i nterv ention and the surveillance of ulcer recurrences or treatment rel ate d adverse events like the development of malignancy. Conclusions There are indications of an advantage for the add-on therapy with growth factors in diabetic foot ulcers concerning complete wound closure and the time to complete wound healing. Further more studies of high methodological quality with adequate sample sizes and sufficient follow-up periods are necessary also investigating patient-relevant parameters like the health-related quality of life, the acceptance and tolerance of the intervention in addition to clinical outcomes. Einleitung Ulcera in Folge von Diabetes mellitus sind aufgrund der zunehmenden Prävalenz der Erkrankung ein schwerwiegendes Problem mit einem großen Anteil an der weltweiten Krankheitslast. Aufgrund langer Krankenhausaufenthalte, Rehabilitation, häufig erforderlicher häuslicher Betreuung und Inanspruchnahme sozialer Dienstleistungen sind diabetische Fußkomplikationen auch teuer. Eine Therapie mit Wachstumsfaktoren könnte eine wirksame innovative Wundbehandlung zusätzlich zu einer Standardwundversorgung darstellen. Forschungsfragen Wie ist der Nutzen einer Therapie mit Wachstumsfaktoren allein oder in Kombination mit anderen Technologien zur Behandlung des diabetischen Fußulcus unter medizinischen, ökonomischen, sozial-ethischen und juristischen Aspekten zu beurteilen? Methodik In relevanten Datenbanken wird eine systematische Literaturrecherche nach englisch- und deutschsprachigen Publikationen seit 1990 durchgeführt. Kostenwerte werden an das Preisniveau von 2008 angepasst und in Euro umgerechnet. Die Überprüfung und Bewertung der methodischen Qualität der medizinischen und ökonomischen Studien erfolgt anhand von anerkannten methodischen Standards der evidenzbasierten Medizin und der Gesundheitsökonomie. Ergebnisse Es können insgesamt 25 Studien identifiziert werden (14 randomisierte kontrollierte Studien (RCT), neun Kosten-Effektivitäts-Analysen und zwei Metaanalysen.In den 14 RCT wird eine zur Standardwundversorgung adjunkte Therapie mit der Standardwundversorgung/Placebo oder einer extrazellulären Wundmatrix verglichen: in sechs Studien Becaplermin, in zwei Studien der rekombinante humane epidermale Wachstumsfaktor (rhEGF), in einer Studie der basische Fibroblastenwachstumsfaktor (bFGF) und in fünf Studien die biologisch aktiven Hautimplantate Dermagraft und Apligraf. Die Studiendauern liegen bei zwölf bis 20 Wochen. Die Studienpopulationen umfassen insgesamt von 17 bis zu 382 Patienten, im Durchschnitt 130.Für eine Behandlung mit Becaplermin, dem Wachstumsfaktor rhEGF und mit den Hautimplantaten Dermagraft und Apligraf zeigt sich im Vergleich zu einer Standardwundversorgung allein in jeweils acht von 13 Studien ein Vorteil hinsichtlich einer vollständigen Wundheilung und der Dauer bis zu einer vollständigen Wundheilung mit statistisch signifikanten Unterschieden. Ein Nachweis für den Nutzen einer Behandlung mit bFGF kann nicht erbracht werden. Die Rate unerwünschter Ereignisse beträgt in vier der 14 Studien mehr als 30% je Studienarm, ist jedoch zwischen den Studiengruppen nicht unterschiedlich. Die methodische Qualität der Studien ist mit deutlichen Mängeln behaftet.Becaplermin kann als kosteneffektiv betrachtet werden. Divergierende Kostengrundlagen und inkrementelle Kosten-Effektivitäts-Relationen lassen eine eindeutige Aussage zu Dermagraft und Apligraf nicht zu. Diskussion Unterschiede in der Standardwundversorgung erschweren den Vergleich der Studienergebnisse miteinander. Vor dem Hintergrund kleiner bis sehr kleiner Studienpopulationen und einer mit deutlichen Mängeln behafteten methodischen Qualität der Studien mit hohem Verzerrungspotential sind die Ergebnisse zur Effektivität und Kosten-Effektivität nur eingeschränkt aussagekräftig. Die Studiendauern und weitere Follow-up-Phasen sind für eine Überprüfung der Nachhaltigkeit der Interventionen und Beobachtung von Ulcusrezidiven oder unerwünschten Ereignisse infolge der Behandlung wie z.B. der Entwicklung maligner Tumoren zu kurz. Schlussfolgerung/Empfehlungen Hinweise auf den Vorteil einer adjunkten Therapie mit Wachstumsfaktoren bei diabetischen Ulcera für eine vollständige Wundheilung und die Dauer bis zu einer vollständigen Wundheilung sind gegeben. Zusätzliche methodisch hochwertige Studien mit adäquaten Fallzahlen und ausreichend langen Nachbeobachtungsphasen sind notwendig, in denen neben klinisch relevanten Zielgrößen auch weitere patientenrelevante Parameter wie z.B. die gesundheitsbezogene Lebensqualität, Akzeptanz und Toleranz der Behandlung untersucht werden.

Scientific background Man-made joints (joint endoprostheses), including knee endoprostheses, are used in some irreversible diseases of the human joints. The implantation of joint endoprostheses (arthroplasty) is associated with an increased risk for infection. To prevent infections, different interventions without and with the use of antibiotics (hygiene procedures and antibiotic prophylaxis) are used. The benefits of these interventions are not clear yet. Research questions The presented report addresses the questions regarding the medical effectiveness, the cost-effectiveness as well as the ethical, social and legal aspects related to the use of interventions to prevent infections after knee arthroplasty. Methods A systematic literature search is conducted in the medical electronic databases MEDLINE, EMBASE, SciSearch etc. in June 2009 and has been completed by a hand search. The analysis includes publications which describe and/or evaluate clinical data from randomized controlled trials (RCT), systematic reviews of RCT, registers of endoprostheses or databases concerning interventions to prevent infections after knee arthroplasty. The conducted literature search also aims to identify health-economic studies and publications dealing explicitly with ethical, social or legal aspects in the use of interventions to prevent infections after knee arthroplasty. The synthesis of information from different publications has been performed qualitatively. Results The systematic literature search yields 1,030 hits. Based on the predefined inclusion and exclusion criteria a total of ten publications is included in the analysis. The presented report does not find evidence of the effectiveness of different hygiene interventions with a high evidence level. Most of the unspecific interventions are recommended on the basis of results from non-RCT, from studies for other clinical indications and/or for clinically not relevant endpoints, as well as on the basis of expert opinions. The evidence of the effectiveness of intravenous prophylaxis with antibiotics in knee arthroplasty on a high level of evidence is also missing. The recommendations use evidence on the intravenous antibiotic prophylaxis transferred from RCT in hip arthroplasty to the arthroplasty of all joints including knee replacement. Moreover, no evidence is found for differences in the effectiveness between various antibiotics in knee arthroplasty. The presented report finds strong hints for the effectiveness of antibiotics in cement in addition to the intravenous prophylaxis; however, evidence of the effectiveness may be accepted only for operating rooms without clean-air measures. Discussion The conclusiveness of the results from non-RCT and from studies for clinically non-relevant endpoints is relatively low. The determined evidence from studies for other clinical indications may be generally transferred to knee replacement operations. Conclusions No proposal to change the recommendations of the Robert Koch Institute with respect to hygiene interventions and intravenous antibiotic prophylaxis can be made from the presented analysis. Also, no recommendations on the selection of certain antibiotic can be derived from the analysed data. The use of antibiotics in cement in addition to the intravenous prophylaxis may be generally recommended. The cost-effectiveness of different interventions to prevent infections in knee arthroplasty remains unclear. There are no signs for concern regarding any ethical, social and/or legal consequences in the use of interventions to prevent infections in knee arthroplasty., GMS Health Technology Assessment; 6:Doc10; ISSN 1861-8863

Introduction Ulcers as a result of diabetes mellitus are a serious problem with an enormous impact on the overall global disease burden due to the increasing prevalence of diabetes. Because of long hospital stays, rehabilitation, often required home care and the use of social services diabetic foot complications are costly. Therapy with growth factors could be an effective and innovative add-on to standard wound care. Research questions What is the benefit of therapies with growth factors alone or in combination with other technologies in the treatment of diabetic foot ulcer assessed regarding medical, economical, social, ethical and juridical aspects? Methods We systematically searched relevant databases limited to English and German language and publications since 1990. Cost values were adjusted to the price level of 2008 and converted into Euro. A review and an assessment of the quality of publications were conducted following approved methodical standards conforming to evidence-based medicine and health economics. Results We identified 25 studies (14 randomized controlled trials (RCT), nine cost-effectiveness analyses, two meta-analyses). The RCT compared an add-on therapy to standard wound care with standard wound care/placebo alone or extracellular wound matrix: in six studies becaplermin, in two rhEGF, in one bFGF, and in five studies the metabolically active skin grafts Dermagraft and Apligraf. The study duration ranged from twelve to 20 weeks and the study population included between 17 to 382 patients, average 130 patients. The treatment with becaplermin, rhEGF and skin implants Dermagraft and Apligraf showed in eight out of 13 studies an advantage concerning complete wound closure and the time to complete wound healing. Evidence for a benefit of treatment with bFGF could not be found. In four out of 14 studies the proportion of adverse events was 30% per study group with no difference between the treatment groups. The methodological quality of the studies was affected by significant deficiencies. The results showed becaplermin being cost-effective whereas no obvious statement can be made regarding Dermagraft and Apligraf because of diverging cost bases and incremental cost-effectiveness ratios. Discussion Differences in standard wound care are complicating the comparison of study results. Taking into consideration the small to very small sample sizes and other methodological flaws with high potential of bias, the validity of the results with regard to effectiveness and cost-effectiveness has to be considered limited. The duration of treatment and follow-up examinations is not long enough to assess the sustainability of the intervention and the surveillance of ulcer recurrences or treatment related adverse events like the development of malignancy. Conclusions There are indications of an advantage for the add-on therapy with growth factors in diabetic foot ulcers concerning complete wound closure and the time to complete wound healing. Further more studies of high methodological quality with adequate sample sizes and sufficient follow-up periods are necessary also investigating patient-relevant parameters like the health-related quality of life, the acceptance and tolerance of the intervention in addition to clinical outcomes., GMS Health Technology Assessment; 6:Doc12; ISSN 1861-8863

Health care policy background Findings from scientific studies form the basis for evidence-based health policy decisions. Scientific background Quality assessments to evaluate the credibility of study results are an essential part of health technology assessment reports and systematic reviews. Quality assessment tools (QAT) for assessing the study quality examine to what extent study results are systematically distorted by confounding or bias (internal validity). The tools can be divided into checklists, scales and component ratings. Research questions What QAT are available to assess the quality of interventional studies or studies in the field of health economics, how do they differ from each other and what conclusions can be drawn from these results for quality assessments? Methods A systematic search of relevant databases from 1988 onwards is done, supplemented by screening of the references, of the HTA reports of the German Agency for Health Technology Assessment (DAHTA) and an internet search. The selection of relevant literature, the data extraction and the quality assessment are carried out by two independent reviewers. The substantive elements of the QAT are extracted using a modified criteria list consisting of items and domains specific to randomized trials, observational studies, diagnostic studies, systematic reviews and health economic studies. Based on the number of covered items and domains, more and less comprehensive QAT are distinguished. In order to exchange experiences regarding problems in the practical application of tools, a workshop is hosted. Results A total of eight systematic methodological reviews is identified as well as 147 QAT: 15 for systematic reviews, 80 for randomized trials, 30 for observational studies, 17 for diagnostic studies and 22 for health economic studies. The tools vary considerably with regard to the content, the performance and quality of operationalisation. Some tools do not only include the items of internal validity but also the items of quality of reporting and external validity. No tool covers all elements or domains. Design-specific generic tools are presented, which cover most of the content criteria. Discussion The evaluation of QAT by using content criteria is difficult, because there is no scientific consensus on the necessary elements of internal validity, and not all of the generally accepted elements are based on empirical evidence. Comparing QAT with regard to contents neglects the operationalisation of the respective parameters, for which the quality and precision are important for transparency, replicability, the correct assessment and interrater reliability. QAT, which mix items on the quality of reporting and internal validity, should be avoided. Conclusions There are different, design-specific tools available which can be preferred for quality assessment, because of its wider coverage of substantive elements of internal validity. To minimise the subjectivity of the assessment, tools with a detailed and precise operationalisation of the individual elements should be applied. For health economic studies, tools should be developed and complemented with instructions, which define the appropriateness of the criteria. Further research is needed to identify study characteristics that influence the internal validity of studies., GMS Health Technology Assessment; 6:Doc07; ISSN 1861-8863

The different actors involved in health system decision-making and regulation have to deal with the question which are valid parameters to assess the health value of health technologies. So called surrogate endpoints represent in the best case preliminary steps in the casual chain leading to the relevant outcome (e. g. mortality, morbidity) and are not usually directly perceptible by patients. Surrogate endpoints are not only used in trials of pharmaceuticals but also in studies of other technologies. Their use in the assessment of the benefit of a health technology is however problematic. In this report we intend to answer the following research questions: Which criteria need to be fulfilled for a surrogate parameter to be considered a valid endpoint? Which methods have been described in the literature for the assessment of the validity of surrogate endpoints? Which methodological recommendations concerning the use of surrogate endpoints have been made by international HTA agencies? Which place has been given to surrogate endpoints in international and German HTA reports? For this purpose, we choose three different approaches. Firstly, we conduct a review of the methodological literature dealing with the issue of surrogate endpoints and their validation. Secondly, we analyse current methodological guidelines of HTA agencies members of the International network of agencies for Health Technology Assessment (INAHTA) as well as of agencies concerned with assessments for reimbursement purposes. Finally, we analyse the outcome parameter used in a sample of HTA reports available for the public. The analysis of methodological guidelines shows a very cautious position of HTA institutions regarding the use of surrogate endpoints in technology assessment. Surrogate endpoints have not been prominently used in HTA reports. None of the analysed reports based its conclusions solely on the results of surrogate endpoints. The analysis of German HTA reports shows a similar pattern. The validation of a surrogate endpoint requires extensive research, including randomized controlled trials (RCT) assessing clinical relevant endpoints. The validity of a surrogate parameter is rather technology-specific than disease-specific. Thus - even in the case of apparently similar technologies - it is necessary to validate the surrogate for every single technology (i. e. for every single active agent). The use of surrogate endpoints in the assessment of the benefit of health technologies is still to be seen very critically. Die Frage nach den Ergebnisparametern, die für eine valide Bewertung des Nutzens medizinischer Technologien verwendet werden können, beschäftigt alle an Entscheidungsfindungen und an der Regulierung im Gesundheitssystem beteiligten Akteure. Während die klinisch relevanten Endpunkte jene sind, die für den Patienten belangvoll sind (z. B. Morbidität, Mortalität), stellen Surrogatendpunkte im besten Fall Vorstufen der eigentlichen klinisch relevanten Endpunkte dar, die für den Patienten in der Regel nicht unmittelbar spürbar sind. Surrogatparameter werden nicht nur in Studien über die Wirksamkeit von Arzneimitteln eingesetzt, sondern auch in Studien zu anderen Technologien. Der Einsatz von Surrogatendpunkten in der Bewertung des Nutzens von Gesundheitstechnologien ist jedoch problematisch. In diesem Bericht wird folgenden Fragen nachgegangen: Welche Kriterien muss ein Surrogatparameter erfüllen, um als valider Endpunkt angesehen werden zu können? Welche Methoden werden zur Validierung von Surrogatendpunkten in der Literatur diskutiert? Welche methodischen Vorgaben machen internationale Agenturen aus dem Bereich Health Technology Assessment (HTA) oder Arzneimittelnutzenbewertung hinsichtlich des Einsatzes von Surrogatendpunkten? Welchen Stellenwert haben Surrogatendpunkte in HTA-Berichten internationaler HTA-Agenturen und in Berichten, die in Deutschland produziert werden? Entsprechend dieser Fragestellungen werden drei verschiedene methodische Herangehensweisen gewählt: Reviews der einschlägigen methodischen Literatur zu Surrogatendpunkten und ihre Validierung, Analyse der aktuellen Methodenpapiere von HTA-Institutionen, Analyse von abgeschlossenen sowie öffentlich zugänglichen internationalen und deutschen HTA-Berichten. Zusammenfassend zeigen die Empfehlungen der hier berücksichtigten Institutionen dahingehend eine kritische Einstellung zur Verwendung von Surrogatendpunkten in HTA. Es lässt sich zudem feststellen, dass Surrogatendpunkte einen geringen Stellenwert in HTA-Berichten haben. In keinem der untersuchten HTA-Berichte wird die Bewertung von nicht diagnostischen Technologien ausschließlich auf die Ergebnisse von Surrogatendpunkten gestützt. Die Ergebnisse der Analyse deutscher HTA-Berichte sind annährend identisch zu denen internationaler. Die Validierung eines Surrogatendpunkts erfordert ausführliche Forschung, einschließlich der Durchführung von randomisierten kontrollierten Studien (RCT) mit klinisch relevanten Endpunkten. Die Validität eines Surogatendpunkts ist eher technologie- als krankheitsspezifisch, so dass die Ergebnisse der Validierung eines Surrogatendpunkts nicht auf andere Technologien übertragen werden können (auch nicht bei einem angeblich ähnlichen Wirkmechanismus). Um ein Höchstmaß an Sicherheit zu erreichen, muss die Validität eines Surrogatendpunkts bei jeder Technologie bzw. jedem Wirkstoff einzeln geprüft werden. Nach wie vor ist der Einsatz von Surrogatendpunkten bei der Nutzenbewertung sehr kritisch zu betrachten.

Orthodontic treatment represents an important fraction in dental interventions. According to other medical methods the question for scientific evidence for the effectiveness of these treatments arises. The question of the effectiveness is connected with the question what is understood as an effect. In principle, the effect of the intervention is understood on the basis of the occlusion or dental health, what disregards further functions of oral health. The generalization to oral health is therefore a necessary consideration in science now. If one appreciates this further development, then there is no one single randomised study available which examines the long-term effect of the orthodontic intervention or for the effects on the oral health. The question, whether the application of a fixed appliance in an orthodontic treatment causes a long-term improvement in oral health, cannot be answered at the present time. The scientific status is the definition of oral health at present. Also the question, whether in the long run the dental health can be improved by fixed appliances cannot be answered with a quality usually achieved by evidence-based medicine. Whether correction of a dental malposition is an effective prerequisite for the preservation of the natural teeth, cannot be answered. There is no generalizing study with sufficient scientific background for Europe or Germany to this topic. The risk for caries cannot be quantified. Caries is identified as a central topic in general but due to numerous factors influencing the risk it is not quantified. The question of the indications is completely open from the scientific literature. For the question of the therapy need or therapy priority some indexes were developed, which lead to a quantification. These indices however are fundamentally criticised by recent research in their meaning and the empirical relevance. There is an impression that there exists a big gap between the practical application and the scientific investigation of this effectiveness of fixed appliances or orthodontic treatment in general. There is much research in the area of diagnostics or further development of appliances or techniques done, however extremely few in the area of need for intervention, analysis of the sustainability; influence factors on the success, like caries or quantification of side effects e. g. root resorption. This research to evaluate the indications is completely lacking, also the required evaluation parameters (e. g. means long-term dental maintenance). This gap is in this respect dubious since a link of determining the demand (inducing demand) and supply in Central European health systems is economically given. This enables to create a possibility for a so-called supply induced demand. To get rid of discussions that the professional work of orthodontics can be near to induced demand or unnecessary indications, research of this topic is quite essential. This requires much stronger information for indications. This can improve confidence for patients and insurance companies. Existing indices like the Index of Treatment Need (IOTN) seem to be of academic interest without practice importance for daily work. The question which indications can be regarded as scientifically proven for the intervention must be given big attention immediately. The individual and subjective assessment of the orthodontist (whose experience is not doubted) has to be considered as not sufficient. The scientific background is absolutely necessary due to ethic reasons for the patient, economic reasons for the social insurance system or financiers and also for the orthodontists to evaluative and legitimates the treatment. Well coordinated research with the goal of collecting specific data is urgently required for individual therapeutic processes with appropriate design. The study quality is also an essential topic. It is unacceptable at the beginning of the 21st century with the background of the evidence based medicine, that studies are published with enormous methodological errors. Orthodontics deserves a well discussed scientific position to prove the enormous individual success and to demonstrate the effectiveness of the developed treatments. Kieferorthopädische Maßnahmen stellen einen bedeutsamen Anteil an zahnmedizinischen Interventionen dar. Wie bei medizinischen Methoden im Generellen stellt sich die Frage, in welcher Weise es wissenschaftliche Belege (Evidenzen) für die Wirksamkeit dieser Maßnahmen gibt. Die Frage der Wirksamkeit ist verbunden mit der Frage, was als Wirkung verstanden wird. Grundsätzlich wird die Wirkung der Intervention auf der Basis der Okklusion bzw. der Zahngesundheit verstanden, was weitere Funktionen des Mundraums außer Acht lässt. Daher ist die Verallgemeinerung auf Mundgesundheit eine nunmehr in der Wissenschaft geforderte Betrachtung. Würdigt man diese Weiterentwicklung, dann ist folglich keine Studie verfügbar, die einerseits die langfristige Wirkung der kieferorthopädischen Intervention untersucht, noch eine die die Auswirkungen auf die Mundgesundheit zum Thema hat. Die Frage, ob sich durch die Anwendung von festsitzenden Apparaten im Rahmen einer kieferorthopädischen Maßnahme eine langfristige Verbesserung des Mundgesundheitszustands ergibt, kann zum gegenwärtigen Zeitpunkt nicht beantwortet werden. Der wissenschaftliche Sachstand beschäftigt sich gegenwärtig mit der Definition von Mundgesundheit. Selbst die Frage, ob die Zahngesundheit durch festsitzende Apparate langfristig verbessert werden kann ist auf der Basis der für die evidenzbasierte Medizin üblichen Qualitätsgüte nicht beantwortbar. Ob die Behebung von Zahnfehlstellungen eine wirksame Voraussetzung für die Erhaltung der natürlichen Bezahnung ist, kann ebenfalls nicht beantwortet werden. Es gibt zu diesem Thema keine verallgemeinerungsfähige Studie mit Aussagekraft für Europa oder Deutschland. Das Risiko für eine Kariesanfälligkeit kann in keiner Weise quantifiziert werden. Karies wird in aller Regel thematisiert, von einer Quantifizierung des Risikos wird in sämtlichen geprüften Studien Abstand genommen, vermutlich da dies von zahlreichen Faktoren, vor allem der Mitarbeit des Patienten abhängt. Die Frage der Indikationsstellungen bleibt aus der wissenschaftlichen Literatur völlig offen. Zwar wurden einige Indizes entwickelt, die der Frage der Therapiebedürftigkeit oder der -priorität eine Quantifizierung verleihen, diese Indizes werden aber in ihrer Aussagekraft und empirischen Relevanz durch jüngere Forschungsarbeiten fundamental in Frage gestellt. Es verstärkt sich der Eindruck, dass eine große Kluft zwischen der praktischen Anwendung kieferorthopädischer Maßnahmen und der wissenschaftlichen Erforschung ihrer Wirksamkeit existiert. Es wird viel Forschungsarbeit im Bereich Diagnostik oder Weiterentwicklung von Geräten oder Techniken erbracht, jedoch äußerst wenig im Bereich Interventionsbedarf, Analyse der Nachhaltigkeit, Einflussfaktoren auf den Erfolg oder Quantifizierung von Nebenwirkungen wie z. B. Karies oder Wurzelresorption. Forschung zur Absicherung der Indikationen fehlt nahezu gänzlich, da auch die erforderlichen Evaluationsparameter (z. B. mittel- bis langfristiger Zahnerhalt) nicht erforscht werden, geschweige denn die Mundgesundheit. Diese Lücke ist insofern bedenklich, da ökonomisch eine Koppelung der Feststellung des Bedarfs (Bedarfsweckung) und der Leistungserbringung in mitteleuropäischen Gesundheitssystemen gegeben ist. Dies eröffnet Rahmenbedingungen für das möglichen Schaffen einer so genannten angebotsinduzierten Nachfrage. Um die professionelle Arbeit der Kieferorthopädie (KFO) nicht in den Nahebereich von Bedarfsinduzierung oder unbelegter Indikationsstellungen zu bringen, ist eine Beforschung dieses Themas ganz wesentlich. Die erforderliche viel stärkere Absicherung von Indikationsstellungen zur Sicherheit und Abgrenzung zu nicht medizinisch gerechtfertigen Leistungen könnte wesentliche Beiträge zur weiteren Vertrauensbildung für Patienten oder Versicherungsgesellschaften schaffen. Die für die Interventionsabsicherung existierenden Indizes, wie der Index of Treatment Need (IOTN), scheinen eine akademische Bedeutung zu haben, die in der täglichen Praxis irrelevant erscheinen. Die Frage, welche Indikationsstellungen nun für die Intervention als wissenschaftlich abgesichert gelten können, muss unverzüglich große Aufmerksamkeit geschenkt werden. Die individuelle und subjektive Einschätzung des Behandlers (dessen Erfahrung nicht in Zweifel gezogen wird) ist für die Durchführung von kieferorthopädischen Maßnahmen als nicht ausreichend zu beurteilen. Die Begründung durch wissenschaftlich gut abgesicherte Studien ist absolut zu fordern, dem Patienten gegenüber aus ethischen, dem Sozialversicherungssystem aus finanziellen und letztendlich auch dem Behandler aus evaluativen und legitimatorischen Gründen. Koordinierte Forschungsvorhaben, die das Ziel der gezielten Datensammlung haben sind vor dem Hintergrund geeigneter Versuchsplanungen für individuelle therapeutische Prozesse dringend erforderlich. Auch die dabei angepeilte Studienqualität ist ein wesentliches Thema. Die Veröffentlichung von methodisch völlig unverwertbaren oder mit zahlreichen offensichtlichen Fehlern behaftete Studien ist zu Beginn des 21. Jahrhunderts vor dem Hintergrund der evidenzbasierten Medizin, der allgemein bekannten Methodenlage und der angespannten Finanzierbarkeit des Gesundheitssystems inakzeptabel. Die KFO verdient sich in Anbetracht der wahrscheinlich zu Recht vermuteten Erfolge auch eine entsprechend qualitativ hoch stehende wissenschaftliche Begleitung und Absicherung ihrer Vorgehensweise.

Background Heart failure is a clinical syndrome of major epidemiological and economical importance. In Germany as in other industrialised countries it is one of the leading causes of mortality, morbidity and disability. For patients not responding to medical therapies ventricular assist devices are used as bridge to transplant, bridge to recovery or as destination therapy alternative to transplantation. Research questions This report aims to present the actual evidence on clinical effectiveness, psychological and social aspects and economical aspects of left ventricular assist devices. Methods We conducted a systematic research of the literature in different databases (EMBASE, MEDLINE, Cochrane Library). The included studies were assessed by two reviewers and were presented in tables and in a narrative form. We also conducted a survey among hospitals using the technology. Results and discussion We included 40 references, six of them were HTA-reports. LVAD patients as bridge to transplant had better survival rates and a better quality of life as compared to medical therapy. Mechanical assistance was associated with frequent and often serious adverse events which were often the cause of death. There were numerous psychological and psychiatric problems. Conclusions/Recommendations LVAD showed to be clinically effective, however with high complications rate and seriousness of them. The use of technology is very costly. Cost-effective should be analysed for Germany. There is a need to further develop the technology before it can contribute seriously to a reduction of the need for heart transplantation. Hintergrund Bei der Herzinsuffizienz handelt es sich um ein Krankheitsbild von großer epidemiologischer und volkswirtschaftlicher Bedeutung. In Deutschland und anderen Industriestaaten gilt sie als eine der führenden Ursachen für Mortalität, Morbidität sowie Erwerbsunfähigkeit. Herzunterstützungssysteme werden bei therapierefraktären Herzinsuffizienz Patienten als Überbrückung zur Herztransplantation (Bridge To Transplant), zur Erholung des Herzens (Bridge To Recovery) oder als langfristige Alternative zur Herztransplantation (Destination Therapy) eingesetzt. Fragestellung Ziel des HTA-Berichts ist die Darstellung der medizinischen Wirksamkeit, der psychosozialen und der ökonomischen Aspekte linksventrikulärer Unterstützungssysteme. Methodik Es erfolgte eine systematische Literaturrecherche in verschiedenen relevanten Datenbanken, unter anderem in EMBASE, in MEDLINE und in der Cochrane Library. Die eingeschlossenen Studien wurden von zwei Autoren bewertet, in Übersichtstabellen dargestellt und narrativ zusammengefasst. Darüber hinaus wurde eine Befragung an Kliniken durchgeführt. Ergebnisse und Diskussion Es wurden 40 Publikationen eingeschlossen, davon waren sechs HTA-Berichte. LVAD-Patienten hatten bessere Überlebensraten und eine bessere Lebensqualität als medikamentös behandelte Patienten. Die Herzunterstützung war assoziiert mit häufigen und oft schwerwiegenden Komplikationen, die auch häufig die Todesursachen darstellten. Es traten zahlreiche psychologische und psychiatrische Probleme auf. Es handelt sich um eine kostenintensive Technologie. Schlussfolgerungen Es besteht Evidenz für die medizinische Effektivität von Herzunterstützungssystemen, wobei die Komplikationsraten und der Schweregrad der Komplikationen noch sehr hoch sind. Kosteneffektivitätsanalysen für Deutschland sind notwendig. Eine Weiterentwicklung der Technologie ist notwendig, bevor diese zur Minderung des Bedarfs an Spenderherzen wirklich beitragen kann.

Research Question The objective of health technology assessment (HTA) is to support decision-making in the health sector by assessing health technologies systematically under medical, economic, social, and ethical aspects. The present study aims at identifying ways of enabling the impact of HTA on decision-making processes in the German health sector. The authors formulate three research questions: (1) Can methods be identified that allow a valid assessment of the impact of HTA reports on the decision-making processes? (2) Has been shown an impact of HTA reports on decision-making processes in the health sector? (3) Which are the factors responsible for a high or a low impact of HTA? Methods The authors include studies that present a methodology to assess the impact of HTA, that investigate the impact of HTA on decision-making processes, or study the factors that might enhance or hinder the impact of HTA. Medical and social science electronic databases, lists of publications and projects of the European, North American, Canadian, and Australian HTA agencies, as well as the bibliography of the identified articles and documents are looked through. The writers do a handsearch of the International Journal of Technology Assessment in Health Care and contact 64 HTA agencies by a letter, requesting information on investigations that might not have been published. Results Abstracts from about 5,000 articles are read. 57 articles are ordered as full-text, 43 are finally included and 14 excluded. (1) In eight studies interviews with decision-makers are used to elicit the information, in three studies document analysis is employed, and in six surveys the results rely only on the observations and interpretations of the authors. One study analyses service data and in nine examinations more than one of the methods listed above are employed. Only in two studies pre-defined indicators were used and only in one clinical trial a prospective design is chosen. (2) In nine studies the impact of a population of HTA reports is analysed: Among these, seven find that more than 70% of the reports have an impact on the decision-making process, in one study 50% of the reports have none or only a minimal impact. In one study on the impact of 50 short HTA reports, it is found that they contribute valuable information but do not influence decisions. However, because of methodological flaws the evidence base for these results is rather limited. Most of the conclusions presented in the publications are based on the appraisal of the authors who are often related to the program of which the impact has been "evaluated". (3) The writers divide the factors that are identified as modifying the degree of impact of the HTA reports in two groups: context factors and factors that are connected to the developing process, the subject, the format, the content, or the quality of the reports. However, the relevance of these factors has to be assessed with caution: none of the publications has the relevance for a primary research question and in none of the studies is the relevance of the factors investigated in a prospective and systematic manner. Conclusion There is little experience with study designs or methods that allow a valid assessment of the impact of HTA reports on the decision-making process in the health sector. However, some approaches, such as the use of pre-defined indicators, were identified that should be pursued and elaborated in further studies. Due to the lack of a developed methodology only limited conclusions related to the impact of HTA reports can be drawn. Among the studies that show a relevant impact, most are methodological. However, results from qualitative studies caution against assuming a causal relationship where a mere coincidence between the recommendations of an HTA report and health policy is identified. In order to produce evidence-based conclusions regarding the impact of HTA reports, validated indicators should be used. Study design should also aim at controlling for other influencing factors. None of the studies explicitly aim at examining the role of the factors that might be responsible for a low or high impact of the HTA reports. The non-systematic retrospective analyses do not allow reliable conclusions regarding the relevance of these factors. Therefore the factors identified here should only serve for hypothesis formation. On the basis of these studies it is not possible to give evidence-based recommendations on the way how to increase the impact of HTA on decision-making in Germany. Instead a concept for evaluation should be developed that combines quantitative and qualitative methods and considers the following questions: (1) What kind of impact should be measured? (2) Which are the target groups and at which level of the health system are they located? (3) Which are the outcome parameters and how can they be measured? (4) Which are the potential impact enhancing or limiting factors? Fragestellung HTA ist eine Methodik zur systematischen und zur transparenten Bewertung medizinischer Verfahren und Technologien unter medizinischen, ökonomischen, sozialen sowie ethischen Aspekten mit dem Ziel, die dazu gehörigen Entscheidungsprozesse zu unterstützen. Ziel dieser Untersuchung ist es, herauszufinden, wie der Einfluss von HTA-Berichten auf gesundheitspolitische Entscheidungsprozesse in Deutschland ermöglicht werden kann. Die Beantwortung dieser Frage wird in drei Felder unterteilt: (1) Gibt es Methoden, die es erlauben, den Einfluss von HTA-Berichten auf die Entscheidungsfindung valide zu bestimmen? (2) Lässt sich ein Einfluss von HTA-Berichten auf die gesundheitspolitische Entscheidungsfindung zeigen? (3) Welche Faktoren sind für einen hohen bzw. einen niedrigen Einfluss verantwortlich? Methodik Eingeschlossen werden Dokumente, die Methoden zur Untersuchung des Einflusses von HTA vorstellen sowie Studien, die den Einfluss von HTA auf Entscheidungsprozesse zum Gegenstand haben oder Faktoren untersuchen, die den Einfluss von HTA stärken oder schwächen. Für den Bericht werden medizinische und sozialwissenschaftliche Datenbanken, Publikations- und Projektlisten von internationalen HTA-Institutionen sowie die Referenzlisten der identifizierten Zeitschriftenaufsätze und Übersichtsarbeiten durchgesehen und durch eine Handsuche ergänzt. 64 HTA-Institutionen werden angeschrieben, um ggf. unveröffentlichte Untersuchungen zu erfassen. Ergebnisse Insgesamt werden die Zusammenfassungen von ca. 5.000 Artikeln durchgesehen. Von diesen werden 57 Artikel aufgrund ihrer Zusammenfassung bestellt. Davon werden 43 ein- und 14 ausgeschlossen. Zu (1) der Fragestellung: In acht Studien werden die Daten durch schriftliche oder mündliche Befragungen von Entscheidungsträgern erhoben, in drei Studien werden Dokumente ausgewertet und bei sechs Untersuchungen beruhen die Angaben ausschließlich auf den Beobachtungen und den Einschätzungen der jeweiligen Autoren. In einem Fall wird der Einfluss anhand von Versorgungsdaten bestimmt. Neun Studien setzen mehr als eine der zuvor genannten Methoden ein. Nur in zwei Studien werden prädefinierte Indikatoren für die Bestimmung des Einflusses verwendet. Lediglich eine Studie wendet ein prospektives Design an. Zu (2) der Fragestellung: In sieben Studien, in denen eine - innerhalb eines definierten Rahmens - vollständige Gruppe von HTA-Berichten hinsichtlich ihres Einflusses untersucht wird, wird konstatiert, dass die Berichte in etwa 70% der Fälle Einfluss auf die Entscheidungsprozesse ausüben. Bei einer weiteren Studie dieser Art hat die Hälfte der Berichte geringen oder keinen Einfluss auf die Entscheidungsprozesse. In einer anderen Untersuchung wird 50 Kurzberichten attestiert, dass sie zwar nützliche Informationen liefern, aber nicht in die Entscheidungen eingeflossen sind. Die diesen Ergebnissen zugrunde liegende Evidenz ist aufgrund methodischer Schwächen jedoch als wenig überzeugend einzuschätzen. Zu (3) der Fragestellung: Die den Einfluss der HTA-Berichte modifizierenden Faktoren werden in Kontextfaktoren und Faktoren, die den Entstehungsprozess, den Gegenstand, das Format, den Inhalt oder die Qualität der Berichte betreffen, unterschieden. Die Validität der identifizierten Faktoren ist jedoch dadurch eingeschränkt, dass ihre Bedeutung in keiner Studie systematisch und prospektiv untersucht wird. Schlussfolgerung Es gibt nur wenige Erfahrung mit Methoden oder Studiendesigns, die eine valide Bewertung des Einflusses von HTA-Berichten auf die gesundheitspolitische Entscheidungsfindung ermöglichen. Es finden sich jedoch einige Ansätze, wie z.B. der Einsatz von prädefinierten Indikatoren, die weiter verfolgt und entwickelt werden können. Aufgrund der unzureichenden Methodik der meisten Studien können nur vorsichtige Aussagen über den Einfluss von HTA-Berichten getroffen werden. Die beiden methodisch aufwendigeren quantitativen Untersuchungen weisen jedoch einen substantiellen Einfluss von HTA-Berichten auf die Entscheidungsfindung nach. Die Ergebnisse der qualitativen Studien warnen aber davor, von der inhaltlichen Übereinstimmung zwischen Empfehlungen aus HTA-Berichten und nachfolgenden Entscheidungen regelmäßig auf einen kausalen Zusammenhang zu schließen. Um evidenzbasierte Schlussfolgerungen über den Einfluss von HTA-Berichten ziehen zu können, wäre es notwendig, hinsichtlich ihrer Validität überprüfte Indikatoren einzusetzen und die Untersuchungen so zu gestalten, dass die Einflüsse anderer Faktoren kontrolliert werden können. Keine der Studien beschäftigt sich systematisch und explizit mit der Fragestellung nach den Faktoren, die für einen hohen bzw. niedrigen Einfluss verantwortlich sind. Die unsystematischen "Mit-Betrachtungen" dieser Frage in den Untersuchungen lassen keine validen Rückschlüsse zu. Die in den Berichten genannten Faktoren können somit lediglich zur Hypothesenbildung für weiterführende Untersuchungen dienen. Auf die Frage, wie man den Einfluss von HTA-Berichten in Deutschland ermöglichen kann, lassen sich auf der Grundlage der hier ausgewerteten Studien keine evidenzbasierten Antworten geben. Stattdessen soll ein Evaluationskonzept entwickelt werden, das quantitative und qualitative Methoden miteinander verbindet sowie folgenden Leitfragen nachgeht: (1) Welche Art von Einfluss soll ausgeübt und gemessen werden? (2) Welche sind die Zielgruppen und auf welcher Ebene des Gesundheitssystems befinden sie sich? (3) Welche sind die Zielparameter und wie lassen sie sich messen? (4) Welche den Einfluss modifizierenden Faktoren sind relevant?

The objective of this Health Technology Assessment (HTA) methods report was to examine and to assess decision analysis (DA) as a method to transfer and adapt international scientific evidence in HTA to the German health care context. Furthermore, we sought to develop a systematic framework to facilitate the selection, transfer, adaptation, and synthesis of these data in German HTA projects.In this report, we review and summarise the concepts and methods of DA; present potential areas of applications, and provide a basis for the critical assessment of decision-analytic studies. The two main methods of DA, decision trees and Markov models, as well as various approaches to sensitivity analyses are described. Examples of typical situations for the use of DA in scientific evidence transfer are described, and a list of main health care domains and parameters in evidence transfer is presented. Finally, we developed a framework to transfer and apply international evidence to the national health care context. The strengths and limitations of the decision-analytic approach are critically examined.In summary, this HTA report describes different situations, in which decision-analytic models can be useful, and demonstrates the utility of DA in transferring and applying international evidence to the national health care context. We developed a systematic instrument to transfer international evidence to the context of other countries and successfully applied this instrument in two German HTA projects. The use of this instrument is recommended in further HTA projects dealing with the application of international evidence to the German health care context. The use of decision-analytic models to transfer international evidence is endorsed. However, the limitations of DA should be clearly stated discussed transparently in all HTA reports. Ziele dieses HTA-Methodenberichts (HTA = Health Technology Assessment) sind die Prüfung und die Bewertung der Entscheidungsanalyse (EA) als methodisches Instrument zur Übertragung sowie zur Anpassung internationaler Evidenz aus dem Bereich HTA auf den Kontext des deutschen Gesundheitssystems. Ferner soll ein systematisches Konzept entwickelt werden, das als Orientierung bei der Auswahl, bei der Übertragung, bei der Anpassung und bei der Zusammenführung dieser Daten im Rahmen deutscher HTA-Projekte dienen kann.Es soll ein Überblick über die Konzepte und Methoden der EA gegeben sowie neben den Anwendungsbereichen, den Möglichkeiten und den Grenzen entscheidungsanalytischer Verfahren die Grundlage für eine kritische Beurteilung entscheidungsanalytischer Studien vermittelt werden. Die beiden wichtigsten Methoden der EA sind das Entscheidungsbaumverfahren und Markov-Modelle. Zusätzlich werden die verschiedenen Formen von Sensitivitätsanalysen dargestellt. Anhand von Beispielen werden Standardsituationen für die Anwendung von EA zur Evidenzübertragung erläutert und zentrale Versorgungsbereiche und Parameter bei der Evidenzübertragung aufgezeigt. Schließlich soll ein Stufenkonzept (Framework) zur Übertragung internationaler Evidenz im Rahmen von HTA auf den nationalen Kontext entwickelt sowie die Stärken und die Limitationen des entscheidungsanalytischen Ansatzes kritisch gewürdigt und herausgearbeitet werden.Zusammenfassend können in diesem HTA-Bericht verschiedene Situationen, in denen sich der Einsatz entscheidungsanalytischer Modelle anbietet, dargestellt und der Nutzen des Einsatzes von EA im Rahmen der Übertragung internationaler Evidenz auf den nationalen Kontext aufgezeigt werden. Es wird ein systematisches Instrumentarium zur Übertragung internationaler Evidenz auf den nationalen Versorgungskontext entwickelt, das in zwei HTA-Projekten erfolgreich angewandt und in weiteren HTA-Projekten, bei denen sich die Problematik der Übertragung von Evidenz aus ausländischen Studien auf den deutschen Kontext stellt, empfohlen wird. Der Einsatz entscheidungsanalytischer Modelle zur Evidenzübertragung wird befürwortet. Er besitzt jedoch verschiedene Limitationen, die in jedem HTA-Bericht transparent dargestellt und kritisch diskutiert werden sollen.