Edmund A. M. Neugebauer

Evidence-based clinical practice guidelines (CPGs) are relevant sources for generating quality indicators (QIs). The objective of this study was to compare guideline-based QIs of German and international CPGs and their underlying methodological approaches. We conducted systematic searches in the guideline databases of G-I-N (Guidelines International Network) and NGC (National Guideline Clearinghouse) between February and June 2017 to identify international CPGs matching the topics of German evidence-based CPGs (n = 35) that report QIs, which were identified in a preceding study. Additionally, we searched the websites of the particular CPG providers for separate documents with regard to QIs. We included evidence-based CPGs which report QIs. Reported QIs, the underlying guideline recommendations, and information on methods of development were extracted. The selection and extraction of CPGs were conducted by one reviewer and checked by another. For each matched pair of CPGs, we assessed whether the suggested QIs matched or were not directly comparable. Twenty-five international CPGs, originating from seven CPG providers in total, met the criteria for inclusion. They matched the topics of 18 German CPGs. This resulted in 30 CPG pairs for the comparison of QIs (some of the international CPGs matched the topic of more than one German CPG). We found 27 QI pairs with QIs “not different or slightly different”, corresponding to 13% (27 of 212) of the QIs in German CPGs and 16% (27 of 166) in international CPGs. Only two QI pairs were judged to be “different/inconsistent”. For 183 of 212 (86%) QIs from German CPGs and 137 of 166 (83%) QIs from international CPGs, no direct comparison could be made. An explicit link to one or more guideline recommendations was found for 136 of 152 (89%) QIs from German CPGs and 82 of 166 (49%) QIs from international CPGs. Some information on methods for the development of QIs existed for 12 of 18 (67%) German CPGs and 8 of 25 (32%) international CPGs. The majority of QIs in German and international CPGs were not comparable. Various reasons for this are conceivable. More transparent reporting of the underlying methods for generating guideline-based QIs is needed.

The AGREE II instrument is the most commonly used guideline appraisal tool. It includes 23 appraisal criteria (items) organized within six domains. AGREE II also includes two overall assessments (overall guideline quality, recommendation for use). Our aim was to investigate how strongly the 23 AGREE II items influence the two overall assessments. An online survey of authors of publications on guideline appraisals with AGREE II and guideline users from a German scientific network was conducted between 10th February 2015 and 30th March 2015. Participants were asked to rate the influence of the AGREE II items on a Likert scale (0 = no influence to 5 = very strong influence). The frequencies of responses and their dispersion were presented descriptively. Fifty-eight of the 376 persons contacted (15.4%) participated in the survey and the data of the 51 respondents with prior knowledge of AGREE II were analysed. Items 7–12 of Domain 3 (rigour of development) and both items of Domain 6 (editorial independence) had the strongest influence on the two overall assessments. In addition, Items 15–17 (clarity of presentation) had a strong influence on the recommendation for use. Great variations were shown for the other items. The main limitation of the survey is the low response rate. In guideline appraisals using AGREE II, items representing rigour of guideline development and editorial independence seem to have the strongest influence on the two overall assessments. In order to ensure a transparent approach to reaching the overall assessments, we suggest the inclusion of a recommendation in the AGREE II user manual on how to consider item and domain scores. For instance, the manual could include an a-priori weighting of those items and domains that should have the strongest influence on the two overall assessments. The relevance of these assessments within AGREE II could thereby be further specified.

Quality indicators (QIs) are used in assessing the quality of healthcare. Evidence-based clinical practice guidelines (CPGs) are relevant sources for generating QIs. In this context, QIs are important tools to assess the implementation of guideline recommendations. However, the methodological approaches to guideline-based QI development vary considerably. In Germany, the guideline classification scheme of the AWMF (German Association of the Scientific Medical Societies) differentiates between S1-, S2k-, S2e-, and S3-CPGs depending on the methodological approach. Thus, S3-CPGs are consensus- and evidence-based CPGs and have the highest methodological standard in Germany. An analysis of the status quo of reported QIs in S3-CPGs found 35 current S3-CPGs, which report 372 different QIs. Currently, there is no gold standard for the development of guideline-based QIs. To our knowledge, no studies have investigated to what extent guideline-based QIs from different CPGs that are related to the same topic are consistent. The objective of this study is to compare guideline-based QIs and their underlying methodological approaches of German S3-CPGs with those of topic-related international CPGs. Based on the previous identified German S3-CPGs (n = 35), which report quality indicators, we will conduct systematic searches in the guidelines databases of G-I-N (Guidelines International Network) and NGC (National Guideline Clearinghouse) to identify international CPGs matching the topics of the S3-CPGs. If necessary, we will search additionally the websites of the particular CPG providers for separate documents with regard to QIs. We will include evidence-based CPGs which report QIs. Reported QIs as well as methods of development and the rationale for QIs will be extracted and compared with those of the S3-CPGs. This study will be part of the project “Systematic analysis of the translation of guideline recommendations into quality indicators and development of an evidence- and consensus-based standard,” supported by the German Research Association (DFG). The results of this analysis will feed into a subsequent qualitative study, which will consist of structured interviews with developers of international CPGs. Further, the results will be considered in a consensus study on standards of the translation of guideline recommendations into quality indicators in Germany.

Immunosuppressive drugs have to be taken through the whole duration of kidney transplant survival to avoid rejection. Low adherence can increase the risk of allograft rejection. The objective was to evaluate the effectiveness of adherence-enhancing interventions (AEI) in kidney transplantation recipients taking immunosuppressive drugs. A search was performed in Medline, Embase, CINAHL, and PsycINFO. The search was performed in May 2016. We included comparative studies on AEI for kidney transplant recipients taking immunosuppressive drugs. The primary outcome was medication adherence. All identified articles were screened according to the predefined inclusion criteria. The risk of bias was assessed with the Cochrane risk of bias tool. Study selection and risk of bias assessment were performed by two reviewers independently. Data were extracted in standardized tables. Data extraction was verified by a second reviewer. All discrepancies were resolved through discussion. Data were synthesized in a structured narrative way. There is no registered or published protocol for this systematic review. We identified 12 studies. The number of participants ranged from 24 to 1830. Nine studies included adults, two children, and one adults and children. Risk of bias was high. The main reasons for high risk of bias were inadequate allocation sequence (confounding) and that studies were not blinded. Eleven studies evaluated AEI consisting of educational and/or behavioral components. All these studies showed an effect direction in favor of the intervention. Intervention effect was only moderate. Most adherence measures in studies on educational and behavioral interventions showed statistically significant differences. Studies that combined educational and behavioral intervention components showed larger effects. All studies that were statistically significant were multimodal. Studies that included an individualized component and more intensive interventions showed larger effects. One study evaluated a reminder system. Effect size was not reported. This study showed no statistical significant difference (p > 0.05). Educational and behavioral AEI can increase adherence. In particular, multimodal and individualized interventions seem promising. However, because of the small effect, the high risk of bias, and the invalidity of adherence measures, the actual benefit of adherence interventions for an unselected patient population (i.e., including also adherent patients) seems limited. No conclusion is possible for interventions combining adherence-enhancing components that address intentional (behavioral) as well as unintentional adherence (reminder).

Evidence-based clinical practice is challenging in all fields, but poses special barriers in the field of rare diseases. The present paper summarises the main barriers faced by clinical research in rare diseases, and highlights opportunities for improvement. Systematic literature searches without meta-analyses and internal European Clinical Research Infrastructure Network (ECRIN) communications during face-to-face meetings and telephone conferences from 2013 to 2017 within the context of the ECRIN Integrating Activity (ECRIN-IA) project. Barriers specific to rare diseases comprise the difficulty to recruit participants because of rarity, scattering of patients, limited knowledge on natural history of diseases, difficulties to achieve accurate diagnosis and identify patients in health information systems, and difficulties choosing clinically relevant outcomes. Evidence-based clinical practice for rare diseases should start by collecting clinical data in databases and registries; defining measurable patient-centred outcomes; and selecting appropriate study designs adapted to small study populations. Rare diseases constitute one of the most paradigmatic fields in which multi-stakeholder engagement, especially from patients, is needed for success. Clinical research infrastructures and expertise networks offer opportunities for establishing evidence-based clinical practice within rare diseases.

Medical devices play an important role in the diagnosis, prevention, treatment and care of diseases. However, compared to pharmaceuticals, there is no rigorous formal regulation for demonstration of benefits and exclusion of harms to patients. The medical device industry argues that the classical evidence hierarchy cannot be applied for medical devices, as randomised clinical trials are impossible to perform. This article aims to identify the barriers for randomised clinical trials on medical devices. Systematic literature searches without meta-analysis and internal European Clinical Research Infrastructure Network (ECRIN) communications taking place during face-to-face meetings and telephone conferences from 2013 to 2017 within the context of the ECRIN Integrating Activity (ECRIN-IA) project. In addition to the barriers that exist for all trials, we identified three major barriers for randomised clinical trials on medical devices, namely: (1) randomisation, including timing of assessment, acceptability, blinding, choice of the comparator group and considerations on the learning curve; (2) difficulties in determining appropriate outcomes; and (3) the lack of scientific advice, regulations and transparency. The present review offers potential solutions to break down the barriers identified, and argues for applying the randomised clinical trial design when assessing the benefits and harms of medical devices.

Evidence-based clinical research poses special barriers in the field of nutrition. The present review summarises the main barriers to research in the field of nutrition that are not common to all randomised clinical trials or trials on rare diseases and highlights opportunities for improvements. Systematic academic literature searches and internal European Clinical Research Infrastructure Network (ECRIN) communications during face-to-face meetings and telephone conferences from 2013 to 2017 within the context of the ECRIN Integrating Activity (ECRIN-IA) project. Many nutrients occur in multiple forms that differ in biological activity, and several factors can alter their bioavailability which raises barriers to their assessment. These include specific difficulties with blinding procedures, with assessments of dietary intake, and with selecting appropriate outcomes as patient-centred outcomes may occur decennia into the future. The methodologies and regulations for drug trials are, however, applicable to nutrition trials. Research on clinical nutrition should start by collecting clinical data systematically in databases and registries. Measurable patient-centred outcomes and appropriate study designs are needed. International cooperation and multistakeholder engagement are key for success.

Randomised clinical trials are key to advancing medical knowledge and to enhancing patient care, but major barriers to their conduct exist. The present paper presents some of these barriers. We performed systematic literature searches and internal European Clinical Research Infrastructure Network (ECRIN) communications during face-to-face meetings and telephone conferences from 2013 to 2017 within the context of the ECRIN Integrating Activity (ECRIN-IA) project. The following barriers to randomised clinical trials were identified: inadequate knowledge of clinical research and trial methodology; lack of funding; excessive monitoring; restrictive privacy law and lack of transparency; complex regulatory requirements; and inadequate infrastructures. There is a need for more pragmatic randomised clinical trials conducted with low risks of systematic and random errors, and multinational cooperation is essential. The present paper presents major barriers to randomised clinical trials. It also underlines the value of using a pan-European-distributed infrastructure to help investigators overcome barriers for multi-country trials in any disease area.

Pancreatic resections are among the most complex procedures in visceral surgery. While mortality has decreased substantially over the past decades, morbidity remains high. The volume-outcome correlation in pancreatic surgery is among the strongest in the field of surgery. The German Society for General and Visceral Surgery (DGAV) established a national registry for quality control, risk assessment and outcomes research in pancreatic surgery in Germany (DGAV SuDoQ|Pancreas). Here, we present the aims and scope of the DGAV StuDoQ|Pancreas Registry. A systematic assessment of registry quality is performed based on the recommendations of the German network for outcomes research (DNVF). The registry quality was assessed by consensus criteria of the DNVF in regard to the domains Systematics and Appropriateness, Standardization, Validity of the sampling procedure, Validity of data collection, Validity of statistical analysis and reports, and General demands for registry quality. In summary, DGAV StuDoQ|Pancreas meets most of the criteria of a high-quality clinical registry. The DGAV StuDoQ|Pancreas provides a valuable platform for quality assessment, outcomes research as well as randomized registry trials in pancreatic surgery.