Search

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.

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.

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 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., GMS Health Technology Assessment; 8:Doc04; ISSN 1861-8863

Background 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. Objective 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). Methods 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. Results 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. Discussion/Conclusion No final statement can be drawn regarding the effectiveness of alternative 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., GMS Health Technology Assessment; 8:Doc03; 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

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 “Patient-Reported Outcome” (PRO) is used as an umbrella term for different concepts for measuring subjectively perceived health status e. g. as treatment effects. Their common characteristic is, that the appraisal of the health status is reported by the patient himself. In order to describe the informative value of PRO in Health Technology Assessment (HTA) first an overview of concepts, classifications and methods of measurement is given. The overview is complemented by an empirical analysis of clinical trials and HTA-reports on rheumatoid arthritis and breast cancer in order to report on type, frequency and consequences of PRO used in these documents. Methods For both issues systematic reviews of the literature have been performed. The search for methodological literature covers the publication period from 1990 to 2009, the search for clinical trials of rheumatoid arthritis and breast cancer covers the period 2005 to 2009. Both searches were performed in the medical databases of the German Institute of Medical Documentation and Information (DIMDI). The search for HTA-reports and methodological papers of HTA-agencies was performed in the CRD-Databases (CRD = Centre for Reviews and Dissemination) and by handsearching the websites of INAHTA member agencies (INAHTA = International Network of Agencies for Health Technology Assessment). For all issues specific inclusion and exclusion criteria were defined. The methodological quality of randomized controlled trials (RCT) was assessed by a modified version of the Cochrane Risk of Bias Tool. For the methodological part information extraction from the literature is structured by the report’s chapters, for the empirical part data extraction sheets were constructed. All information is summarized in a qualitative manner. Results Concerning the methodological issues the literature search retrieved 158 documents (87 documents related to definition or classification, 125 documents related to operationalisation of PRO). For the empirical analyses 225 RCT (rheumatoid arthritis: 77; breast cancer: 148) and 40 HTA-reports and method papers were found. The analysis of the methodological literature confirms the role of PRO as an umbrella term for a variety of different concepts. The newest classification system facilitates the description of PRO measures by construct, target population and the method of measurement. Steps of operationalisation involve defining a conceptual framework, instrument development, exploration of measurement properties or, possibly, the modification of existing instruments. Seven out of 59 RCT analysing the effects of antibody therapy for rheumatoid arthritis define PRO as the primary endpoint, 38 trials utilize composite measures (ACR, DAS) and ten trials report clinical or radiological parameters as the primary endpoint. Six out of 123 chemotherapy trials for breast cancer define PRO as the primary endpoint, while 98 trials report clinical endpoints (survival, tumour response, progression) in their primary analyses. Discrepancies in the number of trials result from inaccurate specifications of endpoints in the publications. This distribution is reflected in the HTA-reports: while almost all reports on rheumatoid arthritis refer to PRO, this is only the case in about half of the reports on breast cancer. Conclusions As definition and classification of PRO are concerned, coherent concepts are found in the literature. Their operationalisation and implementation must be guided by scientific principles. The type and frequency of PRO used in clinical trials largely depend on the disease analysed. The HTA-community seems to pursue the utilization of PRO proactively – in case of missing data the need for further research is stated., GMS Health Technology Assessment; 7:Doc01; ISSN 1861-8863

Background The HTA-report (Health Technology Assessment) deals with over- and undertreatment of pain therapy. Especially in Germany chronic pain is a common reason for the loss of working hours and early retirement. In addition to a reduction in quality of life for the affected persons, chronic pain is therefore also an enormous economic burden for society. Objectives Which diseases are in particular relevant regarding pain therapy? What is the social-medical care situation regarding pain facilities in Germany? What is the social-medical care situation in pain therapy when comparing on international level? Which effects, costs or cost-effects can be seen on the micro-, meso- and macro level with regard to pain therapy? Among which social-medical services in pain therapy is there is an over- or undertreatment with regard to the micro-, meso- and macro level? Which medical and organisational aspects that have an effect on the costs and/or cost-effectiveness have to be particularly taken into account with regard to pain treatment/chronic pain? What is the influence of the individual patient's needs (micro level) in different situations of pain (e. g. palliative situation) on the meso- and macro level? Which social-medical and ethical aspects for an adequate treatment of chronic pain on each level have to be specially taken into account? Is the consideration of these aspects appropriate to avoid over- or undertreatment? Are juridical questions included in every day care of chronic pain patients, mainly in palliative care? On which level can appropriate interventions prevent over- or undertreatment? Methods A systematic literature research is done in 35 databases. In the HTA, reviews, epidemiological and clinical studies and economic evaluations are included which report about pain therapy and in particular palliative care in the years 2005 till 2010. Results 47 studies meet the inclusion criteria. An undertreatment of acupuncture, over- and misuse with regard to opiate prescription and an overuse regarding unspecific chest pain and chronic low back pain (LBP) can be observed. The results show the benefit and the cost-effectiveness of interdisciplinary as well as multi-professional approaches, multimodal pain therapy and cross-sectoral integrated medical care. Only rough values can be determined about the care situation regarding the supply of pain therapeutic and palliative medical facilities as the data are completely insufficient. Discussion Due to the broad research question the HTA-report contains inevitably different outcomes and study designs which partially differ qualitatively very strong from each other. In the field of palliative care hospices for in-patients and palliative wards as well as hospices for out-patients are becoming more and more important. Palliative care is a basic right of all terminally ill persons. Conclusion Despite the relatively high number of studies in Germany the HTA-report shows a massive lack in health care research. Based on the studies a further expansion of out-patient pain and palliative care is recommended. Further training for all involved professional groups must be improved. An independent empirical analysis is necessary to determine over or undertreatment in pain care., GMS Health Technology Assessment; 7:Doc03; ISSN 1861-8863