The role of Homocysteine as a predictor for coronary heart disease

Background and objective: There is an ongoing debate on the role of the cytotoxic aminoacid homocysteine as a causal risk factor for the development of coronary heart disease. Results from multiple case control-studies demonstrate, that there is a strong association between high plasma levels of homoysteine and prevalent coronary heart disease, independent of other classic risk factors. Furthermore, results from interventional studies point out that elevated plasma levels of homocysteine may effectively be lowered by the intake of folic acid and B vitamins. In order to use this information for the construction of a new preventive strategy against coronary heart disease, more information is needed: first, whether homocysteine actually is a causal risk factor with relevant predictive properties and, second, whether by lowering elevated homocysteine plasma concentrations cardiac morbidity can be reduced. Currently in Germany the determination of homocysteine plasma levels is reimbursed for by statutory health insurance in patients with manifest coronary heart disease and in patients at high risk for coronary heart disease but not for screening purposes in asymptomatic low risk populations.Against this background the following assessment sets out to answer four questions: 1. Is an elevated homocysteine plasma concentration a strong, consistent and independent (of other classic risk factors) predictor for coronary heart disease? 2. Does a therapeutic lowering of elevated homoysteine plasma levels reduce the risk of developing coronary events? 3. What is the cost-effectiveness relationship of homocysteine testing for preventive purposes? 4. Are there morally, socially or legally relevant aspects that should be considered when implementing a preventive strategy as outlined above? Methods: In order to answer the first question, a systematic overview of prospective studies and metaanalyses of prospective studies is undertaken. Studies are included that analyse the association of homocysteine plasma levels with future cardiac events in probands without pre-existing coronary heart disease or in population-based samples. To answer the second question, a systematic overview of the literature is prepared, including randomised controlled trials and systematic reviews of randomised controlled trials that determine the effectiveness of homocysteine lowering therapy for the prevention of cardiac events. To answer the third question, economic evaluations of homocysteine testing for preventive purposes are analysed. Methodological quality of all materials is assessed by widely accepted instruments, evidence was summarized qualitatively. Results: For the first question eleven systematic reviews and 33 single studies (prospective cohort studies and nested case control studies) are available. Among the studies there is profound heterogeneity concercing study populations, classification of exposure (homocysteine measurements, units to express “elevation”), outcome definition and measurement, as well as controlling for confounding (qualitatively and quantitatively). Taking these heterogeneities into consideration, metaanalysis of single patient data with controlling for multiple confounders seems to be the only adequate method of summarizing the results of single studies. The only available analysis of this type shows, that in otherwise healthy people homocysteine plasma levels are only a very weak predictor of future cardiac events. The predictive value of the classical risk factors is much stronger. Among the studies that actively exclude patients with pre-existing coronary heart disease, there are no reports of an association between elevated homocysteine plasma levels and future cardiac events. Eleven randomized controlled trials (ten of them reported in one systematic review) are analysed in order to answer the second question. All trials include high risk populations for the development of (further) cardiac events. These studies also present with marked clinical heterogeneity: primarily concerning the average homocysteine plasma levels at baseline, type and mode of outcome measurement and as study duration. Except for one, none of the trials shows a risk reduction for cardiac events by lowering homocysteine plasma levels with folate or B vitamins. These results also hold for predefined subgroups with markedly elevated homocysteine plasma levels. In order to answer the third questions, three economic evaluations (modelling studies) of homocysteine testing are available. All economic models are based on the assumption that lowering homocysteine plasma levels results in risk reduction for cardiac events. Since this assumption is falsified by the results of the interventional studies cited above, there is no evidence left to answer the third question. Morally, socially or legally relevant aspects of homocysteine assessment are currently not being discussed in the scientific literature. Discussion and conclusion: Many currently available pieces of evidence contradict a causal role of homocysteine in the pathogenesis of coronary heart disease. Arguing with the Bradford-Hill criteria at least the criterion of time-sequence (that exposure has to happen before the outcome is measured), the criterion of a strong and consistent association and the criterion of reversibility are not fulfilled. Therefore, homocysteine may, if at all, play a role as a risk indicator but not as risk factor. Furthermore, currently available evidence does not imply that for the prevention of coronary heart disease, knowledge of homocysteine plasma levels provides any information that supersedes the information gathered from the examination of classical risk factors. So, currently for the indication of prevention, there is no evidence that homocysteine testing provides any benefit. Against this background there is also no basis for cost-effectiveness calculations. Further basic research should clarify the discrepant results of case control studies and prospective studies. Maybe there is a third parameter (confounder) associated with homocysteine metabolism as well with coronary heart disease. Further epidemiological research could elucidate the role of elevated homocysteine plasma levels as a risk indicator or prognostic indicator in patients with pre-existing coronary heart disease taking into consideration the classical risk factors

Informative value of Patient Reported Outcomes (PRO) in Health Technology Assessment (HTA)

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 radiol ogic al 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.Hintergrund und Zielsetzung Patient-Reported Outcome (PRO) wird als Oberbegriff für unterschiedliche Konzepte zur Messung subjektiv empfundener Gesundheitszustände verwendet. Sie sind dadurch gekennzeichnet, dass der Patient selbst seine Einschätzung berichtet. Um den Stellenwert von PRO im Kontext von HTA-Verfahren (HTA = Health Technology Assessment) zu beschreiben, wird zunächst eine Übersicht über Konzepte, Klassifikationen und methodische Messansätze erstellt. Diese Übersicht wird ergänzt um eine empirische Analyse von klinischen Studien und HTA-Berichten mit dem Ziel, Art, Häufigkeit und Konsequenzen der verwendeten PRO zu dokumentieren. Methodik Beide Fragestellungen werden mithilfe von systematischen Literaturübersichten bearbeitet. Für den methodischen Teil wird in den medizinnahen Datenbanken des Deutschen Instituts für Medizinische Dokumentation und Information (DIMDI) mit einer Recherchestrategie aus drei Modulen im Zeitraum von 1990 bis 2009 gesucht. Die Recherche nach randomisierten klinischen Studien (RCT) zu den Krankheitsbildern rheumatoide Arthritis (RA) und Mammakarzinom erfolgt ebenfalls in den Datenbanken des DIMDI, für den Zeitraum von 2005 bis 2009. Die Recherche nach HTA-Berichten und -Methodenpapieren umfasst die Datenbanken des Centre for Reviews and Dissemination (CRD) und Handsuchen. Für alle Fragestellungen werden spezifische Ein- und Ausschlusskriterien zur Literaturselektion definiert. Die methodische Qualität der RCT wird mithilfe eines in Anlehnung an das "Risk of Bias Tool" der Cochrane Collaboration konzipierten Instruments bewertet. Die Informationsextraktion erfolgt für den methodischen Teil strukturiert durch die Kapitelgliederung, für den empirischen Teil in Extraktionsbögen. Alle Informationen werden qualitativ beschreibend zusammengefasst. Ergebnisse Aus den Recherchen können 158 Dokumente zur Bearbeitung der methodischen Fragestellungen (87 Dokumente zu Definition/Klassifikation; 125 Dokumente zur Operationalisierung) und 225 RCT (77 RA, 148 Mammakarzinom) sowie 40 HTA-Berichte zur Bearbeitung der empirischen Fragestellungen gewonnen werden. Die Analysen zu Definitionen bestätigen PRO als Oberbegriff für eine Vielzahl von patientenberichteten Endpunkten. Das neueste Klassifikationssystem ermöglicht die Beschreibung der PRO nach dem Konstrukt, der Zielpopulation und der Messmethode. Ausführungen zur Operationalisierung beziehen sich auf den Konzeptrahmen, die Instrumentenentwicklung, -eigenschaften und -modifikationsmöglichkeiten. Von 59 Studien zur Antikörpertherapie der RA verwenden sieben ausschließlich PRO, 38 gemischte Zielgrößen (American College of Rheumatology [ACR], Disease Activity Score [DAS]) und zehn rein klinische bzw. radiologische Parameter als primäre Outcomes. Von 123 Studien zur Chemotherapie des Mammakarzinoms stützen sich nur sechs auf PRO als primäre Zielgröße; 98 Studien gebrauchen klinische Parameter (Überlebenszeit, Tumoransprechen, Progression). Abweichungen von der Gesamtzahl resultieren aus ungenauen Angaben der Zielgrößen. Diese Verteilung spiegelt sich auch in den analysierten HTA-Berichten wieder. In den Berichten zur RA werden durchweg PRO-Zielgrößen berichtet, während in den Berichten zum Mammakarzinom dies in knapp der Hälfte der Publikationen der Fall ist. Zusammenhänge zwischen Studienqualität und der Verwendung von PRO sind nicht erkennbar. Schlussfolgerungen Für die Definition und die Klassifikation von PRO existieren inzwischen schlüssige Konzepte, deren Umsetzung wissenschaftlichen Kriterien genügen muss. Die Häufigkeit und die Art der in klinischen Studien verwendeten PRO variieren abhängig vom untersuchten Krankheitsbild. Im Kontext von HTA wird die Notwendigkeit zur Erfassung von PRO wahrgenommen, bei fehlenden Daten wird Forschungsbedarf formuliert

Prevention of relapsing backache

Background: The condition of non-specific back pain is characterized by high prevalence, non satisfactory therapeutic options and severe socioeconomic consequences. Therefore prevention seems an attractive option to downsize the problem. However, the construction of effective preventive measures is complicated by the obscure aetiology of the condition, the multidimensionality of risk and prognostic factors (bio psychosocial model!) and the variability of its natural as well as clinical course. This led to the development of a wide variety of preventive measures: e. g. exercise programs, educational measures (including back school), ergonomic modification of the work environment, mechanical supports (e. g. back belts) as well as multidisciplinary interventions. For two reasons the workplace seems to be a suitable setting for prevention. First, because a number of strong risk factors are associated with working conditions and second, because it allows addressing a large proportion of the adult population. Against this background the assessment at hand sets out to answer the following questions: What is the amount and methodological quality of the available scientific literature on the effectiveness of back pain prevention in the workplace environment? What are effective measures for the prevention of back pain and its consequences in the workplace environment and how effective are they? Is back pain prevention in the workplace environment cost-effective? Is there a need for more research? As primary outcomes for effectiveness the assessment will focus on time lost from work and the frequency and duration of episodes with back pain. The preventive measures assessed belong to the following categories: exercise programs, educational and information measures, multidimensional interventions, back belts, lifting teams and ergonomic interventions. Methods: The assessment is based on a systematic review of the published literature according to the methodological requirements of DAHTA. Proceedings of the electronic literature searches are documented in the appendix. In addition references of review articles were searched. Methodological quality of publications (systematic reviews, HTA reports) was assessed using the checklists developed by the German Scientific Working Group for Technology Assessment in Health Care (GSWGTAHC) or with the Jadad-Score (controlled trials) respectively. Due to the large number of relevant publications the assessment is mainly based on data reported by systematic reviews and supplemented by the results of newer trials. A separate economic assessment was not performed because of the low amount of available data. An assessment of ethical, legal and social impact was omitted due to resource constraints.ResultsFor preventive interventions based on exercise programs most of the analysed trials demonstrate some effectiveness. Due to the heterogeneity of the programs it is not possible to conclude whether positive effects are associated with a special type, duration or intensity of exercise. For purely educational measures or information strategies applied in a workplace setting the available trials were not able to demonstrate effectiveness. Back school programs, which in addition to theoretical instructions offer intensive exercising may in the short term, be successful in reducing the incidence of new episodes of back pain. Some trials in high risk groups demonstrate effectiveness of multidimensional interventions on time lost from work. These programs include education and exercise as well as cognitive behavioural interventions to change pain perception. The assessment of the benefits of back belts for the prevention of back pain is based on results of high quality efficacy as well as effectiveness trials. Their results imply for the otherwise healthy working population no protective effect of back belts on time lost from work due to back pain, on the incidence of painful episodes or on days with impairment by back pain. So far there are no data from controlled trials that demonstrate the effectiveness of "lifting teams" in nursing care to prevent back pain or its consequences. However, results from uncontrolled pilot studies indicate a potential for effectiveness. Among "ergonomic interventions" three different approaches have to be distinguished: interventions addressing changes of the workplace setting, interventions addressing the individual's behaviour and combined interventions. Studies evaluating the effectiveness of setting interventions (modification of the physical workplace environment, changes of production processes, organisational changes) yield no dependable results. This conclusion is not based on indifferent trial results but rather on the lack of methodologically sound studies. Results from studies on ergonomic interventions addressing the individual confirm the conclusions drawn for exercise and educational measures. The most marked results are found in trials that examine the effectiveness of combined interventions in high risk groups and contain a strong participatory component. Hardly any of the trials studying the effects of ergonomic interventions satisfied methodological quality criteria that are accepted standard for clinical or public health intervention studies. There were no data allowing firm conclusions on the cost-effectiveness of interventions from any of the categories. Discussion: The significance of the results of the assessment at hand is strongly limited by the comprehensiveness of the questions addressed. Reviewing the literature on the basis of (even systematic) review articles impairs the differentiated examination of the role of target groups, program contents, application and duration, effect sizes and context factors. While the methodological quality of the review articles is quite high, the quality of individual trials (even those included in the review papers) is highly variable. While most trials examining preventive interventions addressed at individuals satisfy at least some methodological requirements many studies dealing with setting interventions do not. Conclusions: In conclusion, sound scientific evidence for the effectiveness and cost-effectiveness of back pain prevention in the workplace environment is still quite scarce. Further research should include: * The development of interventions guided by the bio psychosocial model of back pain aetiology that combines individual prevention as well as measures addressing the workplace environment. * The integration of results from basic ergonomic research into prevention concepts and the conduct of trials focussing outcomes with relevance to health. * at the workplace setting. * The conduct of qualitative studies to identify factors that impair the effectiveness of prevention programs (e. g. motivation, compliance, people skills). * The integration of cost-effectiveness evaluations into all interventional studies

Falls prevention for the elderly

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

Methods for assessment of innovative medical technologies during early stages of development

Conventional Health Technology Assessment (HTA) is usually conducted at a point in time at which the development of the respective technology may no longer be influenced. By this time developers and/or purchasers may have misinvested resources. Thus the demand for Technology Assessment (TA) which incorporates appropriate methods during early development stages of a technology becomes apparent. Against this health political background, the present report describes methods for a development-accompanying assessment of innovative medical technologies. Furthermore, international research programmes set out to identify or apply such methods will be outlined. A systematic literature search as well as an extensive manual literature search are carried out in order to obtain literature and information. The greatest units of the identified methods consist of assessment concepts, decision support methods, modelling approaches and methods focusing on users and their knowledge. Additionally, several general-purpose concepts have been identified. The identified research programmes INNO-HTA and MATCH (Multidisciplinary-Assessment-of-Technology-Centre-for-Healthcare) are to be seen as pilot projects which so far have not been able to generate final results. MATCH focuses almost entirely on the incorporation of the user-perspective regarding the development of non-pharmaceutical technologies, whereas INNO-HTA is basically concerned with the identification and possible advancement of methods for the early, socially-oriented technology assessment. Most references offer only very vague descriptions of the respective method and the application of greatly differing methods seldom exceeds the character of a pilot implementation. A standardisation much less an institutionalisation of development-accompanying assessment cannot be recognized. It must be noted that there is no singular method with which development-accompanying assessment should be carried out. Instead, a technology and evaluation specific method selection seem to be necessary as medical innovations are diverse and none of the methods are exhaustive. Because of a variety of issues (e. g. ideal time of evaluation, lack of data and uncertainty of data) a development-accompanying assessment should not replace a comprehensive HTA, but rather form a possible preceding step in a multi-staged HTA-process. A final appraisal of the methods for development-accompanying assessment cannot be made based on the available sources. However, the present review may serve as a starting point for further development and application of these methods as well as further examination of the concept of development-accompanying assessment. There is a substantial need for further research concerning the application, validation and comparison of the various methods for development-accompanying assessment

Indirect comparisons of therapeutic interventions

Health political background: The comparison of the effectiveness of health technologies is not only laid down in German law (Social Code Book V, § 139 and § 35b) but also constitutes a central element of clinical guidelines and decision making in health care. Tools supporting decision making (e. g. Health Technology Assessments (HTA)) are therefore in need of a valid methodological repertoire for these comparisons. Scientific background: Randomised controlled head-to-head trials which directly compare the effects of different therapies are considered the gold standard methodological approach for the comparison of the efficacy of interventions. Because this type of trial is rarely found, comparisons of efficacy often need to rely on indirect comparisons whose validity is being controversially debated. Research questions: Research questions for the current assessment are: Which (statistical) methods for indirect comparisons of therapeutic interventions do exist, how often are they applied and how valid are their results in comparison to the results of head-to-head trials? Methods: In a systematic literature research all medical databases of the German Institute of Medical Documentation and Information (DIMDI) are searched for methodological papers as well as applications of indirect comparisons in systematic reviews. Results of the literature analysis are summarized qualitatively for the characterisation of methods and quantitatively for the frequency of their application. The validity of the results from indirect comparisons is checked by comparing them to the results from the gold standard – a direct comparison. Data sets from systematic reviews which use both direct and indirect comparisons are tested for consistency by of the z-statistic. Results: 29 methodological papers and 106 applications of indirect methods in systematic reviews are being analysed. Four methods for indirect comparisons can be identified: 1. Unadjusted indirect comparisons include, independent of any comparator, all randomised controlled trials (RCT) that provide a study arm with the intervention of interest. 2. Adjusted indirect comparisons 3. and metaregression analyses include only those studies that provide one study arm with the intervention of interest and another study arm with a common comparator. While the aforementioned methods use conventional metaanalytical techniques, 4. Mixed treatment comparisons (MTC) use Bayesian statistics. They are able to analyse a complex network of RCT with multiple comparators simultaneously. During the period from 1999 to 2008 adjusted indirect comparisons are the most commonly used method for indirect comparisons. Since 2006 an increase in the application of the more methodologically challenging MTC is being observed. For the validity check 248 data sets, which include results of a direct and an indirect comparison, are available. The share of statistically significant discrepant results is greatest in the unadjusted indirect comparisons (25,5% [95% CI: 13,1%; 38%]), followed by metaregression analyses (16,7% [95% CI: -13,2%; 46,5%]), adjusted indirect comparisons (12,1% [95% CI: 6,1%; 18%]) and MTC (1,8% [95% CI: -1,7%; 5,2%]). Discrepant results are mainly detected if the basic assumption for an indirect comparison – between-study homogeneity – does not hold. However a systematic over- or underestimation of the results of direct comparisons by any of the indirectly comparing methods was not observed in this sample. Discussion: The selection of an appropriate method for an indirect comparison has to account for its validity, the number of interventions to be compared and the quality as well as the quantity of available studies. Unadjusted indirect comparisons provide, contrasted with the results of direct comparisons, a low validity. Adjusted indirect comparisons and MTC may, under certain circumstances, give results which are consistent with the results of direct comparisons. The limited number of available reviews utilizing metaregression analyses for indirect comparisons currently prohibits empirical evaluation of this methodology. Conclusions/Recommendations: Given the main prerequisite – a pool of homogenous and high-quality RCT – the results of head-to-head trials may be pre-estimated by an adjusted indirect comparison or a MTC. In the context of HTA and guideline development they are valuable tools if there is a lack of a direct comparison of the interventions of interest

Adaptation and validation of a German version of the Multimorbidity Treatment Burden Questionnaire

BACKGROUND: Patients with multiple long-term conditions often face a variety of challenges arising from the requirements of their health care. Knowledge of perceived treatment burden is crucial for optimizing treatment. In this study, we aimed to create a German version of the Multimorbidity Treatment Burden Questionnaire (MTBQ) and to evaluate its validity. METHODS: The steps to translate the MTBQ included forward/back translation, cognitive interviews (n = 6) and a pilot test (n = 7). Psychometric properties of the scale were assessed in a cross-sectional survey with primary care patients aged 65 and older with at least 3 long-term conditions (n = 344). We examined the distribution of responses, dimensionality, internal reliability and construct validity. RESULTS: Cognitive interviewing and piloting led to minor modifications and showed overall good face validity and acceptability. As expected, we observed a positively skewed response distribution for all items. Reliability was acceptable with McDonald’s omega = 0.71. Factor analysis suggested one common factor while model fit indices were inconclusive. Predefined hypotheses regarding the construct validity were supported by negative associations between treatment burden and health-related quality of life, self-rated health, social support, patient activation and medication adherence, and positive associations between treatment burden and number of comorbidities. Treatment burden was found to be higher in female participants (Mdn(1) = 6.82, Mdn(2) = 4.55; U = 11,729, p = 0.001) and participants with mental health diagnoses (Mdn(1) = 9.10, Mdn(2) = 4.55; U = 3172, p = 0.024). CONCLUSIONS: The German MTBQ exhibited good psychometric properties and can be used to assess the perceived treatment burden of patients with multimorbidity. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12955-022-01993-z

Testing the HTA Core Model: Experiences from two pilot projects

Objectives: The aim of this study was to analyze and describe process and outcomes of two pilot assessments based on the HTA Core Model, discuss the applicability of the model, and explore areas of development. Methods: Data were gathered from HTA Core Model and pilot Core HTA documents, their validation feedback, questionnaires to investigators, meeting minutes, emails, and discussions in the coordinating team meetings in the Finnish Office for Health Technology Assessment (FINOHTA). Results: The elementary structure of the HTA Core Model proved useful in preparing HTAs. Clear scoping and good coordination in timing and distribution of work would probably help improve applicability and avoid duplication of work. Conclusions: The HTA Core Model can be developed into a platform that enables and encourages true HTA collaboration in terms of distribution of work and maximum utilization of a common pool of structured HTA information for national HTA report