[Are the assessments of individual out-of-pocket health services of the IGeL-Monitor in line with clinical guidelines?] / Stehen die Bewertungen von Individuellen Gesundheitsleistungen (IGeL) des IGeL-Monitors im Einklang mit Leitlinien?

OBJECTIVES: The IGeL-Monitor of the Federal Medical Advisory Service in Germany evaluates the benefits and harms of individual out-of-pocket health services (in German: Individuelle Gesundheitsleistungen / IGeL). The aim of the analysis was to systematically compare IGeL-assessements with the recommendations from evidence-based guidelines. METHOD: To identify guidelines, we conducted searches in guidelines databases (AWMF, Guidelines International Network and Trip database) and the websites of guideline organisations (February/March 2022). We included guidelines that were not older than 5 years. The methodological quality of the guidelines was assessed using the AGREE II instrument. We compared the recommendations with the IGeL-assessments in terms of content and grade of recommendation. RESULTS: We identified 41 guidelines covering 24 IGeL-assessements. 19 (79%) assessments (nearly) were in agreement with the guideline recommendations. No comparison was possible for 5 IGeL-assessements, because, for example, the recommendations were more specific. Ten of the 13 IGeL that were rated (tendentially) negatively were also not recommended in the guidelines. CONCLUSION: Overall, the IGeL-assessments were consistent with the recommendations of current guidelines. Accordingly, guideline groups seem to assess the evidence similarly to the IGeL-Monitor team. Insured persons should be informed honestly about the evidence, particularly for the (tendentially) negatively evaluated IGeL that are not recommended even in guidelines.

Pay for performance for hospitals.

BACKGROUND: Pay-for-Performance (P4P) is a payment model that rewards health care providers for meeting pre-defined targets for quality indicators or efficacy parameters to increase the quality or efficacy of care. OBJECTIVES: Our objective was to assess the impact of P4P for in-hospital delivered health care on the quality of care, resource use and equity. Our objective was not only to answer the question whether P4P works in general (simple perspective) but to provide a comprehensive and detailed overview of P4P with a focus on analyzing the intervention components, the context factors and their interrelation (more complex perspective). SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, three other databases and two trial registers on 27 June 2018. In addition, we searched conference proceedings, gray literature and web pages of relevant health care institutions, contacted experts in the field, conducted cited reference searches and performed cross-checks of included references and systematic reviews on the same topic. SELECTION CRITERIA: We included randomized trials, cluster randomized trials, non-randomized clustered trials, controlled before-after studies, interrupted time series and repeated measures studies that analyzed hospitals, hospital units or groups of hospitals and that compared any kind of P4P to a basic payment scheme (e.g. capitation) without P4P. Studies had to analyze at least one of the following outcomes to be eligible: patient outcomes; quality of care; utilization, coverage or access; resource use, costs and cost shifting; healthcare provider outcomes; equity; adverse effects or harms. DATA COLLECTION AND ANALYSIS: Two review authors independently screened all citations for inclusion, extracted study data and assessed risk of bias for each included study. Study characteristics were extracted by one reviewer and verified by a second.We did not perform meta-analysis because the included studies were too heterogenous regarding hospital characteristics, the design of the P4P programs and study design. Instead we present a structured narrative synthesis considering the complexity as well as the context/setting of the intervention. We assessed the certainty of evidence using the GRADE approach and present the results narratively in 'Summary of findings' tables. MAIN RESULTS: We included 27 studies (20 CBA, 7 ITS) on six different P4P programs. Studies analyzed between 10 and 4267 centers. All P4P programs targeted acute or emergency physical conditions and compared a capitation-based payment scheme without P4P to the same capitation-based payment scheme combined with a P4P add-on. Two P4P program used rewards or penalties; one used first rewards and than penalties; two used penalties only and one used rewards only. Four P4P programs were established and evaluated in the USA, one in England and one in France.Most studies showed no difference or a very small effect in favor of the P4P program. The impact of each P4P program was as follows.Premier Hospital Quality Incentive Demonstration Program: It is uncertain whether this program, which used rewards for some hospitals and penalties for others, has an impact on mortality, adverse clinical events, quality of care, equity or resource use as the certainty of the evidence was very low.Value-Based Purchasing Program: It is uncertain whether this program, which used rewards for some hospitals and penalties for others, has an impact on mortality, adverse clinical events or quality of care as the certainty of the evidence was very low. Equity and resource use outcomes were not reported in the studies, which evaluated this program.Non-payment for Hospital-Acquired Conditions Program: It is uncertain whether this penalty-based program has an impact on adverse clinical events as the certainty of the evidence was very low. Mortality, quality of care, equity and resource use outcomes were not reported in the studies, which evaluated this program.Hospital Readmissions Reduction Program: None of the studies that examined this penalty-based program reported mortality, adverse clinical events, quality of care (process quality score), equity or resource use outcomes.Advancing Quality Program: It is uncertain whether this reward-/penalty-based program has an impact on mortality as the certainty of the evidence was very low. Adverse clinical events, quality of care, equity and resource use outcomes were not reported in any study.Financial Incentive to Quality Improvement Program: It is uncertain whether this reward-based program has an impact on quality of care, as the certainty of the evidence was very low. Mortality, adverse clinical events, equity and resource use outcomes were not reported in any study.Subgroup analysis (analysis of modifying design and context factors)Analysis of P4P design factors provides some hints that non-payments compared to additional payments and payments for quality attainment (e.g. falling below specified mortality threshold) compared to quality improvement (e.g. reduction of mortality by specified percent points within one year) may have a stronger impact on performance. AUTHORS' CONCLUSIONS: It is uncertain whether P4P, compared to capitation-based payments without P4P for hospitals, has an impact on patient outcomes, quality of care, equity or resource use as the certainty of the evidence was very low (or we found no studies on the outcome) for all P4P programs. The effects on patient outcomes of P4P in hospitals were at most small, regardless of design factors and context/setting. It seems that with additional payments only small short-term but non-sustainable effects can be achieved. Non-payments seem to be slightly more effective than bonuses and payments for quality attainment seem to be slightly more effective than payments for quality improvement.

Laparoscopic versus open surgery for suspected appendicitis.

BACKGROUND: The removal of the acute appendix is one of the most frequently performed surgical procedures. Open surgery associated with therapeutic efficacy has been the treatment of choice for acute appendicitis. However, in consequence of the evolution of endoscopic surgery, the operation can also be performed with minimally invasive surgery. Due to smaller incisions, the laparoscopic approach may be associated with reduced postoperative pain, reduced wound infection rate, and shorter time until return to normal activity.This is an update of the review published in 2010. OBJECTIVES: To compare the effects of laparoscopic appendectomy (LA) and open appendectomy (OA) with regard to benefits and harms. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), Ovid MEDLINE and Embase (9 February 2018). We identified proposed and ongoing studies from World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP), ClinicalTrials.gov and EU Clinical Trials Register (9 February 2018). We handsearched reference lists of identified studies and the congress proceedings of endoscopic surgical societies. SELECTION CRITERIA: We included randomised controlled trials (RCTs) comparing LA versus OA in adults or children. DATA COLLECTION AND ANALYSIS: Two review authors independently selected studies, assessed the risk of bias, and extracted data. We performed the meta-analyses using Review Manager 5. We calculated the Peto odds ratio (OR) for very rare outcomes, and the mean difference (MD) for continuous outcomes (or standardised mean differences (SMD) if researchers used different scales such as quality of life) with 95% confidence intervals (CI). We used GRADE to rate the quality of the evidence. MAIN RESULTS: We identified 85 studies involving 9765 participants. Seventy-five trials included 8520 adults and 10 trials included 1245 children. Most studies had risk of bias issues, with attrition bias being the largest source across studies due to incomplete outcome data.In adults, pain intensity on day one was reduced by 0.75 cm on a 10 cm VAS after LA (MD -0.75, 95% CI -1.04 to -0.45; 20 RCTs; 2421 participants; low-quality evidence). Wound infections were less likely after LA (Peto OR 0.42, 95% CI 0.35 to 0.51; 63 RCTs; 7612 participants; moderate-quality evidence), but the incidence of intra-abdominal abscesses was increased following LA (Peto OR 1.65, 95% CI 1.12 to 2.43; 53 RCTs; 6677 participants; moderate-quality evidence).The length of hospital stay was shortened by one day after LA (MD -0.96, 95% CI -1.23 to -0.70; 46 RCTs; 5127 participant; low-quality evidence). The time until return to normal activity occurred five days earlier after LA than after OA (MD -4.97, 95% CI -6.77 to -3.16; 17 RCTs; 1653 participants; low-quality evidence). Two studies showed better quality of life scores following LA, but used different scales, and therefore no pooled estimates were presented. One used the SF-36 questionnaire two weeks after surgery and the other used the Gastro-intestinal Quality of Life Index six weeks and six months after surgery (both low-quality evidence).In children, we found no differences in pain intensity on day one (MD -0.80, 95% CI -1.65 to 0.05; 1 RCT; 61 participants; low-quality evidence), intra-abdominal abscesses after LA (Peto OR 0.54, 95% CI 0.24 to 1.22; 9 RCTs; 1185 participants; low-quality evidence) or time until return to normal activity (MD -0.50, 95% CI -1.30 to 0.30; 1 RCT; 383 participants; moderate-quality evidence). However, wound infections were less likely after LA (Peto OR 0.25, 95% CI 0.15 to 0.42; 10 RCTs; 1245 participants; moderate-quality evidence) and the length of hospital stay was shortened by 0.8 days after LA (MD -0.81, 95% CI -1.01 to -0.62; 6 RCTs; 316 participants; low-quality evidence). Quality of life was not reported in any of the included studies. AUTHORS' CONCLUSIONS: Except for a higher rate of intra-abdominal abscesses after LA in adults, LA showed advantages over OA in pain intensity on day one, wound infections, length of hospital stay and time until return to normal activity in adults. In contrast, LA showed advantages over OA in wound infections and length of hospital stay in children. Two studies reported better quality of life scores in adults. No study reported this outcome in children. However, the quality of evidence ranged from very low to moderate and some of the clinical effects of LA were small and of limited clinical relevance. Future studies with low risk of bias should investigate, in particular, the quality of life in children.

Guideline appraisal with AGREE II: online survey of the potential influence of AGREE II items on overall assessment of guideline quality and recommendation for use.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

[Patients are Satisfied with the Physician-Patient Communication: A Pilot Study Applying the "Individual Clinician Feedback" Questionnaire]. / Patienten zeigen sich zufrieden mit der Arzt-Patienten-Kommunikation ­ eine Pilotstudie mit dem "Individual Clinician Feedback"- Fragebogen.

AIM OF THE STUDY: Patient-centeredness as an essential aspect of quality of patient care is becoming increasingly important. The aim of the pilot study is to gain insight into the physician-patient communication from the patient's perspective. A German questionnaire in a maximum care hospital was tested. METHODS: The German "Individual Clinician Feedback" questionnaire (ICF) was tested in a pilot study in the special consultation in a voluntary cohort of surgeons. In the survey period from June to August 2015, the questionnaire was given to the patient. The physicians received their assessment results as a compressed score. They were rated on a scale of 1-10 on which 10 is "very good". RESULTS: 12 physicians were recruited from five departments. There was a high response rate of 46% (n=219). The patients evaluated the communication as very good (on average over all items and physicians 8.5 to 9.5 points). 89% of the patients had the feeling that the doctor took adequate time for them, while 50% of the patients had a consultation time of 11-20 min. 12% of the patients had still open questions after treatment that they did not ask. 19% and 21% of patients reported that the physician has not asked them if they had any questions, or that they just forgot about it at the end of treatment. CONCLUSION: The results of the pilot study are associated with a good response rate and patients were mostly very satisfied with the physician-patient communication. However, a selection bias among participating physicians is likely.

DEFINING THE RELEVANT OUTCOME MEASURES IN MEDICAL DEVICE ASSESSMENTS: AN ANALYSIS OF THE DEFINITION PROCESS IN HEALTH TECHNOLOGY ASSESSMENT.

BACKGROUND: Defining relevant outcome measures for clinical trials on medical devices (MD) is complex, as there is a large variety of potentially relevant outcomes. The chosen outcomes vary widely across clinical trials making the assessment in evidence syntheses very challenging. The objective is to provide an overview on the current common procedures of health technology assessment (HTA) institutions in defining outcome measures in MD trials. METHODS: In 2012-14, the Web pages of 126 institutions involved in HTA were searched for methodological manuals written in English or German that describe methods for the predefinition process of outcome measures. Additionally, the institutions were contacted by email. Relevant information was extracted. All process steps were performed independently by two reviewers. RESULTS: Twenty-four manuals and ten responses from the email request were included in the analysis. Overall, 88.5 percent of the institutions describe the type of outcomes that should be considered in detail and 84.6 percent agree that the main focus should be on patient relevant outcomes. Specifically related to MD, information could be obtained in 26 percent of the included manuals and email responses. Eleven percent of the institutions report a particular consideration of MD related outcomes. CONCLUSIONS: This detailed analysis on common procedures of HTA institutions in the context of defining relevant outcome measures for the assessment of MD shows that standardized procedures for MD from the perspective of HTA institutions are not widespread. This leads to the question if a homogenous approach should be implemented in the field of HTA on MD.

Laparoscopic versus open appendectomy in patients with suspected appendicitis: a systematic review of meta-analyses of randomised controlled trials.

BACKGROUND: Several systematic reviews (SRs) of randomised controlled trials (RCTs) comparing laparoscopic versus open appendectomy have been published, but there has been no overview of SRs of these two interventions. This overview (review of review) aims to summarise the results of such SRs in order to provide the most up to date evidence, and to highlight discordant results. METHODS: Medline, Embase, Cinahl, the Cochrane Database of Systematic Reviews and the Database of Abstracts of Reviews of Effects were searched for SRs published up to August 2014. Study selection and quality assessment using the AMSTAR tool were carried out independently by two reviewers. We used standardised forms to extract data that were analysed descriptively. RESULTS: Nine SRs met the inclusion criteria. All were of moderate to high quality. The number of randomized controlled trials (RCTs) they included ranged from eight to 67. The duration of surgery pooled by eight reviews was 7.6 to 18.3 minutes shorter using the open approach. Pain scores on the first postoperative day were lower after laparoscopic appendectomy in two out of three reviews. The risk of abdominal abscesses was higher for laparoscopic surgery in half of six meta-analyses. The occurrence of wound infections pooled by all reviews was lower after laparoscopic appendectomy. One review showed no difference in mortality. The laparoscopic approach shortened hospital stay from 0.16 to 1.13 days in seven out of eight meta-analyses, though the strength of the evidence was affected by strong heterogeneity. CONCLUSION: Laparoscopic and open appendectomy are both safe and effective procedures for the treatment of acute appendicitis. This overview shows discordant results with respect to the magnitude of the effect but not to the direction of the effect. The evidence from this overview may prove useful for the development of clinical guidelines and protocols.

Studies analysing the need for health-related information in Germany - a systematic review.

BACKGROUND: Exploring health-related information needs is necessary to better tailor information. However, there is a lack of systematic knowledge on how and in which groups information needs has been assessed, and which information needs have been identified. We aimed to assess the methodology of studies used to assess information needs, as well as the topics and extent of health-related information needs and associated factors in Germany. METHODS: A systematic search was performed in Medline, Embase, Psycinfo, and all databases of the Cochrane Library. All studies investigating health-related information needs in patients, relatives, and the general population in Germany that were published between 2000 and 2012 in German or English were included. Descriptive content analysis was based on predefined categories. RESULTS: We identified 19 studies. Most studies addressed cancer or rheumatic disease. Methods used were highly heterogeneous. Apart from common topics such as treatment, diagnosis, prevention and health promotion, etiology and prognosis, high interest ratings were also found in more specific topics such as complementary and alternative medicine or nutrition. Information needs were notable in all surveyed patient groups, relatives, and samples of the general population. Younger age, shorter duration of illness, poorer health status and higher anxiety and depression scores appeared to be associated with higher information needs. CONCLUSION: Knowledge about information needs is still scarce. Assuming the importance of comprehensive information to enable people to participate in health-related decisions, further systematic research is required.

Improving the adherence of type 2 diabetes mellitus patients with pharmacy care: a systematic review of randomized controlled trials.

BACKGROUND: Oral medication for patients with type 2 diabetes mellitus plays an important role in diabetes care and is associated with a high level self-care behavior and self-management. However, poor adherence to diabetes treatment is common which causes severe health complications and increased mortality. Barriers to adherence may consist of complex treatment regimens often along with long-term multi-therapies, side effects due to the medication as well as insufficient, incomprehensible or confusing information or instructions provided by the health care provider. Multidisciplinary approaches can support adherence success and can enable a more effective management of diabetes care. One approach in diabetes care can be the involvement of a pharmacist. The aim was to analyze the effectiveness of adherence-enhancing pharmacist interventions for oral medication in type 2 diabetes mellitus. METHODS: A systematic review of randomized controlled trials. The study quality was assessed with the Cochrane risk of bias tool. RESULTS: Of 491 hits, six publications were included. Two studies mainly examining educational interventions showed a significant improvement in adherence. Moreover, the quality of the included studies was deficient. CONCLUSION: Although pharmacist interventions might potentially improve adherence to type 2 diabetes mellitus medication, high-quality studies are needed to assess effectiveness.

Guidance on how to efficiently find, choose, and use available systematic reviews was developed.

OBJECTIVES: The aim of this paper is to provide clinicians and authors of clinical guidelines or patient information with practical guidance on searching and choosing systematic reviews(s) (SR[s]) and, where adequate, on making use of SR(s). STUDY DESIGN AND SETTING: At the German conference of the Evidence-Based Medicine Network (EbM Network) a workshop on the topic was held to identify the most important areas where guidance for practice appears necessary. After the workshop, we established working groups. These included SR users with different backgrounds (eg, information specialists, epidemiologists) and working areas. Each working group developed and consented a draft guidance based on their expert knowledge and experiences. The results were presented to the entire group and finalized in an iterative process. RESULTS: We developed a practical guidance that answers questions that usually arise when choosing and using SR(s). (1) How to efficiently find high-quality SRs? (2) How to choose the most appropriate SR? (3) What to do if no SR of sufficient quality could be identified? In addition, we developed an algorithm that links these steps and accounts for their interaction. The resulting guidance is primarily directed at clinicians and developers of clinical practice guidelines or patient information resources. CONCLUSION: We suggest practical guidance for making the best use of SRs when answering a specific research question. The guidance may contribute to the efficient use of existing SRs. Potential benefits when using existing SRs should be always weighted against potential limitations.

Cost-effectiveness of adherence interventions for highly active antiretroviral therapy: a systematic review.

OBJECTIVES: The objective of this systematic review was to evaluate the cost-effectiveness of interventions aiming to increase the adherence to highly active antiretroviral therapy (HAART) in HIV-infected patients in developed countries (WHO stratum A). METHODS: A systematic search for comparative health economic studies was conducted in the following databases: EMBASE, MEDLINE, NHS Economic Evaluation Database, CINAHL, HEED, and EconLit. The identified publications were selected by two reviewers independently according to predefined inclusion and exclusion criteria. Furthermore, these were evaluated according to a standardized checklist and finally extracted, analyzed, and summarized. RESULTS: After reviewing the abstracts and full texts four relevant studies were identified. Different educational programs were compared as well as the Directly Observed Therapy (DOT). A critical aspect to be considered in particular was the poor transparency of the cost data. In three cost-utility analyses the costs per quality-adjusted life-year (QALY) in the baseline scenario were each under USD 15,000. The sensitivity analyses with a presumed maximum threshold of USD 50,000/QALY showed a predominantly cost-effective result. In one study that examined DOT the costs add up to over USD 150,000/QALY. CONCLUSIONS: It seems that adherence interventions for HAART in HIV-infected patients can be cost-effective. Nevertheless, the quality of the included studies is deficient and only a few of the possible adherence interventions are taken into consideration. A final assessment of the cost-effectiveness of adherence interventions in general is, therefore, not possible.

Systematic review of current guideline appraisals performed with the Appraisal of Guidelines for Research & Evaluation II instrument-a third of AGREE II users apply a cut-off for guideline quality.

OBJECTIVES: To investigate whether Appraisal of Guidelines for Research & Evaluation (AGREE) II users apply a cut-off based on standardized domain scores or overall guideline quality to distinguish between high- and low-quality guidelines, as well as to investigate which criteria they use to generate this cut-off and which type of cut-off they apply. STUDY DESIGN AND SETTING: We conducted a systematic search in MEDLINE, EMBASE, DARE, and the HTA-database for German- and English-language studies appraising guidelines with AGREE II. Information on cut-offs was extracted and analyzed descriptively. RESULTS: We identified 118 relevant publications. Thirty-nine (33%) used a cut-off, of which 24 (62%) used a 2-step and 13 (33%) used a 3-step approach. The cut-off for high quality lay between 50% and 70% (2-step) and 60% and 83% (3-step) of the highest possible rating. Twenty-four (62%) publications applied a cut-off based on standardized domain scores and 7 (18%) based on overall guideline quality. Eleven (28%) applied cut-offs to derive the recommendation for guideline use. CONCLUSION: A third of AGREE II users apply a cut-off to distinguish between high- and low-quality guidelines, often without clearly describing how the cut-off is generated. Many users might welcome a clear distinction between high- and low-quality guidelines; specifying a cut-off for this purpose might be useful.

A systematic decision-making process on the need for updating clinical practice guidelines proved to be feasible in a pilot study.

OBJECTIVES: The objective of this study was to test and evaluate a new decision-making process on the need for updating within the update of a German clinical practice guideline (CPG). STUDY DESIGN AND SETTING: The pilot study comprised (1) limited searches in Pubmed to identify new potentially relevant evidence, (2) an online survey among the members of the CPG group to assess the need for update, and (3) a consensus conference for determination and prioritization of guideline sections with a high need for update. Subsequently, we conducted a second online survey to evaluate the procedure. RESULTS: The searches resulted in 902 abstracts that were graded as new potentially relevant evidence. Twenty five of 39 members of the CPG group (64%) participated in the online survey. Seventy six percent of those took part in the second online survey. The evaluation study found on average a grade of support of the procedure regarding the determination of the need for update of 3.65 (standard deviation: 0.76) on a likert scale with 1 = "no support" to 5 = "very strong support." CONCLUSION: The conducted procedure presents a systematic approach for assessing whether and to what extent a CPG requires updating and enables setting priorities for which particular guideline section to update within a CPG.

Guideline appraisal with AGREE II: Systematic review of the current evidence on how users handle the 2 overall assessments.

INTRODUCTION: The Appraisal of Guidelines for Research & Evaluation (AGREE) II instrument is the most commonly used guideline appraisal tool. It includes 23 appraisal criteria (items) organized within 6 domains and 2 overall assessments (1. overall guideline quality; 2. recommendation for use). The aim of this systematic review was twofold. Firstly, to investigate how often AGREE II users conduct the 2 overall assessments. Secondly, to investigate the influence of the 6 domain scores on each of the 2 overall assessments. MATERIALS AND METHODS: A systematic bibliographic search was conducted for publications reporting guideline appraisals with AGREE II. The impact of the 6 domain scores on the overall assessment of guideline quality was examined using a multiple linear regression model. Their impact on the recommendation for use (possible answers: "yes", "yes, with modifications", "no") was examined using a multinomial regression model. RESULTS: 118 relevant publications including 1453 guidelines were identified. 77.1% of the publications reported results for at least one overall assessment, but only 32.2% reported results for both overall assessments. The results of the regression analyses showed a statistically significant influence of all domains on overall guideline quality, with Domain 3 (rigour of development) having the strongest influence. For the recommendation for use, the results showed a significant influence of Domains 3 to 5 ("yes" vs. "no") and Domains 3 and 5 ("yes, with modifications" vs. "no"). CONCLUSIONS: The 2 overall assessments of AGREE II are underreported by guideline assessors. Domains 3 and 5 have the strongest influence on the results of the 2 overall assessments, while the other domains have a varying influence. Within a normative approach, our findings could be used as guidance for weighting individual domains in AGREE II to make the overall assessments more objective. Alternatively, a stronger content analysis of the individual domains could clarify their importance in terms of guideline quality. Moreover, AGREE II should require users to transparently present how they conducted the assessments.

A systematic literature review of evidence-based clinical practice for rare diseases: what are the perceived and real barriers for improving the evidence and how can they be overcome?

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Specific barriers to the conduct of randomised clinical trials on medical devices.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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 practice: Overview of threats to the validity of evidence and how to minimise them.

Using the best quality of clinical research evidence is essential for choosing the right treatment for patients. How to identify the best research evidence is, however, difficult. In this narrative review we summarise these threats and describe how to minimise them. Pertinent literature was considered through literature searches combined with personal files. Treatments should generally not be chosen based only on evidence from observational studies or single randomised clinical trials. Systematic reviews with meta-analysis of all identifiable randomised clinical trials with Grading of Recommendations Assessment, Development and Evaluation (GRADE) assessment represent the highest level of evidence. Even though systematic reviews are trust worthier than other types of evidence, all levels of the evidence hierarchy are under threats from systematic errors (bias); design errors (abuse of surrogate outcomes, composite outcomes, etc.); and random errors (play of chance). Clinical research infrastructures may help in providing larger and better conducted trials. Trial Sequential Analysis may help in deciding when there is sufficient evidence in meta-analyses. If threats to the validity of clinical research are carefully considered and minimised, research results will be more valid and this will benefit patients and heath care systems.

Systematic review found AMSTAR, but not R(evised)-AMSTAR, to have good measurement properties.

OBJECTIVES: To summarize all available evidence on measurement properties in terms of reliability, validity, and feasibility of the Assessment of Multiple Systematic Reviews (AMSTAR) tool, including R(evised)-AMSTAR. STUDY DESIGN AND SETTING: MEDLINE, EMBASE, Psycinfo, and CINAHL were searched for studies containing information on measurement properties of the tools in October 2013. We extracted data on study characteristics and measurement properties. These data were analyzed following measurement criteria. RESULTS: We included 13 studies, four of them were labeled as validation studies. Nine articles dealt with AMSTAR, two articles dealt with R-AMSTAR, and one article dealt with both instruments. In terms of interrater reliability, most items showed a substantial agreement (>0.6). The median intraclass correlation coefficient (ICC) for the overall score of AMSTAR was 0.83 (range 0.60-0.98), indicating a high agreement. In terms of validity, ICCs were very high with all but one ICC lower than 0.8 when the AMSTAR score was compared with scores from other tools. Scoring AMSTAR takes between 10 and 20 minutes. CONCLUSION: AMSTAR seems to be reliable and valid. Further investigations for systematic reviews of other study designs than randomized controlled trials are needed. R-AMSTAR should be further investigated as evidence for its use is limited and its measurement properties have not been studied sufficiently. In general, test-retest reliability should be investigated in future studies.

The transcatheter aortic valve implementation (TAVI)--a qualitative approach to the implementation and diffusion of a minimally invasive surgical procedure.

BACKGROUND: The transcatheter aortic valve implantation (TAVI), a minimally invasive surgical procedure to treat patients with severe symptomatic aortic stenosis, showed a rapid diffusion in Germany compared to the international level. The aim of this study is to identify and analyze factors affecting the implementation and diffusion of the procedure in hospitals using a qualitative application of the diffusion of innovations theory. METHODS: We conducted problem-centered interviews with cardiologists and cardiac surgeons working in German hospitals. The multi-level model "diffusion of innovations in health services organizations" developed by Greenhalgh et al. was used to guide the research. Data was analyzed using content and a thematic analysis. RESULTS: Among the ten participants who were interviewed, we found both barriers and facilitators related to the innovation itself, system readiness and antecedents, communication and influence, and the outer context. Key issues were the collaboration between cardiologists and cardiac surgeons, reimbursement policies, requirements needed to conduct the procedure, and medical advantages of the method. CONCLUSIONS: The findings show that there are multiple factors influencing the diffusion of TAVI that go beyond the reimbursement and cost issues. The diffusion of innovations model proved to be helpful in understanding the different aspects of the uptake of the procedure. A central theme that affected the implementation of TAVI was the collaboration and competition between involved medical departments: cardiology and cardiac surgery. Against this background, it seems especially important to moderate and coordinate the cooperation of the different medical disciplines.