Evaluation of 'implications for research' statements in systematic reviews of interventions in advanced cancer patients - a meta-research study.

BACKGROUND: Implications for research (IfR) sections are an important part of systematic reviews (SRs) to inform health care researchers and policy makers. PRISMA 2020 recommends reporting IfR, while Cochrane Reviews require a separate chapter on IfR. However, it is unclear to what extent SRs discuss IfR. We aimed i) to assess whether SRs include an IfR statement and ii) to evaluate which elements informed IfR statements. METHODS: We conducted a meta-research study based on SRs of interventions in advanced cancer patients from a previous project (CRD42019134904). As suggested in the Cochrane Handbook, we assessed if the following predefined variables were referred to in IfR statements: patient, intervention, control, outcome (PICO) and study design; concepts underlying Grading of Recommendations, Assessment, Development and Evaluation (GRADE) domains: risk of bias, inconsistency, indirectness, imprecision, publication bias. Data were independently extracted by three reviewers after piloting the data extraction form. Discrepancies were resolved in weekly in-depth discussions. RESULTS: We included 261 SRs. The majority evaluated a pharmacological intervention (n = 244, 93.5%); twenty-nine were Cochrane Reviews (11.1%). Four out of five SRs included an IfR statement (n = 210, 80.5%). IfR statements commonly addressed 'intervention' (n = 121, 57.6%), 'patient ' (n = 113, 53.8%), and 'study design' (n = 107, 51.0%). The most frequent PICO and study design combinations were 'patient and intervention ' (n = 71, 33.8%) and 'patient, intervention and study design ' (n = 34, 16.2%). Concepts underlying GRADE domains were rarely used for informing IfR recommendations: 'risk of bias ' (n = 2, 1.0%), and 'imprecision ' (n = 1, 0.5%), 'inconsistency ' (n = 1, 0.5%). Additional elements informing IfR were considerations on cost effectiveness (n = 9, 4.3%), reporting standards (n = 4, 1.9%), and individual patient data meta-analysis (n = 4, 1.9%). CONCLUSION: Although about 80% of SRs included an IfR statement, the reporting of PICO elements varied across SRs. Concepts underlying GRADE domains were rarely used to derive IfR. Further work needs to assess the generalizability beyond SRs in advanced cancer patients. We suggest that more specific guidance on which and how IfR elements to report in SRs of interventions needs to be developed. Utilizing PICO elements and concepts underlying GRADE according to the Cochrane Handbook to state IfR seems to be a reasonable approach in the interim. REGISTRATION: CRD42019134904.

[How to interpret the certainty of evidence based on GRADE (Grading of Recommendations, Assessment, Development and Evaluation)]. / Wie sich die Vertrauenswürdigkeit von Evidenz anhand von GRADE ("grading of recommendations, assessment, development and evaluation") interpretieren lässt.

BACKGROUND: GRADE (Grading of Recommendations, Assessment, Development and Evaluation) is a widely used approach in the fields of medicine and public health to assess the outcome-specific certainty of the evidence in systematic reviews. OBJECTIVES: To make the GRADE approach comprehensible in order to facilitate the reading, understanding and interpretation of GRADE assessments in systematic reviews. MATERIALS AND METHODS: Presentation of the procedure of the GRADE approach using the example of a Cochrane review on selenium supplements in the prevention of prostate cancer. RESULTS: GRADE provides criteria for rating the certainty of evidence. GRADE's approach to rating the certainty of the evidence is based on a four-level system (high, moderate, low, very low). The GRADE approach classifies bodies of randomized controlled trials as initially starting at high certainty and bodies of observational studies at initially starting at low certainty. By assessing the five domains (risk for bias, inconsistency, indirectness, insufficient precision and publication bias), certainty can be rated down or, in the case of large effects, existing dose-response relationships or plausible confounders, rated up. CONCLUSIONS: GRADE is a consistent and transparent approach for rating the certainty of a body of evidence by offering explicit key questions.

[Risk of bias in controlled clinical trials]. / Bias in kontrollierten Studien.

Results from clinical studies are often subject to the risk of bias (deviation from the truth, systematic error). Therefore, a critical appraisal of studies provides a useful strategy in evidence-based healthcare to safeguard against wrong decisions and resulting in overtreatment or undertreatment. This article explains the frequently encountered types of bias, differentiates between them and provides strategies for avoidance of systematic errors. In addition, the two established Cochrane tools with which the risk of bias can be assessed in randomized and non-randomized studies are presented. To highlight the most important components of these tools for bias assessment, examples of randomization, confounding, blinding, completeness of data and selective reporting are provided. Finally, it is shown that bias should not be confused with other study limitations, such as external validity and imprecision.

Prevalence of hearing loss and use of hearing aids among children and adolescents in Germany: a systematic review.

BACKGROUND: Current data suggest that approximately 466 million people (5.0%) of the world's population have disabling hearing loss, therefrom, 34 million children, impacting their quality of life. To provide estimates on the prevalence of hearing loss on a national level, we reviewed the epidemiological literature addressing hearing loss in children and adolescents living in Germany as an example for a Western country. METHODS: We searched Medline, Web of Science, Cochrane Library, ScienceDirect and LIVIVO to identify published data. Furthermore, we manually searched websites of relevant institutions and journals not listed in electronically and searched for ongoing studies and/or not yet published data in clinicaltrials.gov . Study selection, data extraction, and methodological assessment were carried out by two reviewers. RESULTS: In total, 11 reports provided data with sample sizes ranging from 310 up to more than 14 million children and adolescents. Prevalence data were collected by interviews (self-assessments), using pure-tone audiometry or the international classification of diseases (ICD-10) coding and ranged from 0.1 to 128 per 1000 children. Although the estimate of the prevalence of hearing loss goes down, when the threshold was raised, generating a comprehensive and coherent set of estimates proved challenging owing to clinical heterogeneity including variation in age, the study setting, the definition of hearing loss and the assessment method. Moreover, representativeness (external validity) was often impaired owing to estimates lacking currentness (i.e., referring to former West Germany) or selected (patient) data and may not be typical for a more general population. CONCLUSIONS: In conclusions, this work raises public awareness of the high prevalence of hearing loss, highlights issues associated with epidemiological research and is of great importance for researcher and those who use epidemiological data to inform clinical and political decision making.

[Risk of bias in controlled clinical trials]. / Bias in kontrollierten Studien.

Results from clinical studies are often subject to the risk of bias (deviation from the truth, systematic error). Therefore, a critical appraisal of studies provides a useful strategy in evidence-based healthcare to safeguard against wrong decisions and resulting in overtreatment or undertreatment. This article explains the frequently encountered types of bias, differentiates between them and provides strategies for avoidance of systematic errors. In addition, the two established Cochrane tools with which the risk of bias can be assessed in randomized and non-randomized studies are presented. To highlight the most important components of these tools for bias assessment, examples of randomization, confounding, blinding, completeness of data and selective reporting are provided. Finally, it is shown that bias should not be confused with other study limitations, such as external validity and imprecision.

McMaster RARE-Bestpractices clinical practice guideline on diagnosis and management of the catastrophic antiphospholipid syndrome.

Background The McMaster RARE-Bestpractices project group selected the catastrophic antiphospholipid syndrome (CAPS) for a pilot exercise in guideline development for a rare disease. Objectives The objectives of this exercise were to provide a proof of principle that guidelines can be developed for rare diseases and assist in clinical decision making for CAPS. Patients/Methods The GIN-McMaster Guideline Development checklist and GRADE methodology were followed throughout the guideline process. The CAPS guideline was coordinated by a steering committee, and the guideline panel was formed with representation from all relevant stakeholder groups. Systematic reviews were performed for the key questions. To supplement the published evidence, we piloted novel methods, including use of an expert-based evidence elicitation process and ad hoc analysis of registry data. Results This paper describes the CAPS guideline recommendations, including evidence appraisal and discussion of special circumstances and implementation barriers identified by the panel. Many of these recommendations are conditional, because of subgroup considerations in this heterogeneous disease, as well as variability in patient values and preferences. Conclusions The CAPS clinical practice guideline initiative met the objective of the successful development of a clinical practice guideline in a rare disease using GRADE methodology. We expect that clinicians caring for patients with suspected CAPS will find the guideline useful in assisting with diagnosis and management of this rare disease.

Evidence gaps in ENT surgery - a qualitative survey.

Introduction: As in other disciplines, the burgeoning knowledge in ENT medicine long ago surpassed our ability to adequately absorb it and maintain a proper overview. This can give rise to actual or assumed evidence gaps that can impede the progress of the discipline and evidence-based treatment of patients. Clinics and medical practices also hold to traditional doctrines that shape day-to-day medicine, without these schools being challenged based on evidence. Methods: Between February and June 2015, 160 ENT clinics, including 34 university hospitals, and 2,670 ENT practices took part in a two-arm online survey on existing or perceived evidentiary gaps in ENT medicine using a previously developed questionnaire. The survey used for half of the participants was open in form; the other half were given a closed survey with systematics of the field for orientation. The survey was augmented with additional data such as the number of publications and focus areas in the clinics and the age and type of practice of the established physicians. Results: The return rate from the clinics was 39.7%; the return rate of the closed surveys was 29.3%. Of the physicians in medical practice, 14.6% responded to the closed and 18.6% to the open survey. There were no major differences between the two forms of survey. Otological and oncological issues comprised approximately 30% of the list of answers from clinics. Corresponding questions were formulated regarding the current diagnostic and therapeutic problems, such as with stage-related tumor treatment or implantable hearing aids. Diagnostic procedures, e.g., special new procedures in audiology and vestibulogy, dominated the surveys from the practices. However clinics and practices alike cited marginal areas of the discipline that are of daily relevance. Discussion: The cited evidence gaps then needed to be verified or refuted and clarified based on research of the literature as to whether the existing evidence actually reached healthcare providers in the form of guidelines, publications, conferences, or continuing training for application in daily practice. Other steps would include prioritizing future research, evidence mapping, deciding on further systematic reviews, and targeted studies in conjunction with procuring third-party funding and in cooperation with patient associations. The knowledge thus gained should ultimately be transferred in improved form for application in daily clinical practice. Ten questions of key importance each needed to be formulated for the hospitals and practices.

[Gaps of Evidence in ENT-Surgery - a Qualitative Survey]. / Qualitative Umfrage zur Identifizierung von Evidenzlücken in der HNO-Heilkunde.

INTRODUCTION: As in other disciplines, the burgeoning knowledge in ENT medicine long ago surpassed our ability to adequately absorb it and maintain a proper overview. This can give rise to actual or assumed knowledge gaps that can impede the progress of the discipline and evidence-based treatment of patients. Clinics and medical practices also hold to traditional doctrines that shape day-to-day medicine, without these schools being challenged based on evidence. METHODS: Between February and June 2015, 160 ENT clinics, including 34 university hospitals, and 2,670 ENT practices took part in a two-arm online survey on existing or perceived evidentiary gaps in ENT medicine using a previously development questionnaire. The survey used for half the participants was open in form; the other half were given a closed survey with systematics of the field for orientation. The survey was augmented with additional data such as the number of publications and focus areas in the clinics and the age and type of practice of the established physicians. RESULTS: The return rate from the clinics was 39.7%; the return rate of the closed surveys was 29.3%. Of the physicians in medical practice, 14.6% responded to the closed and 18.6% to the open survey. There were no major differences between the two forms of survey. Otological and oncological issues comprised approximately 30% of the list of answers from clinics. Corresponding questions were formulated regarding the current diagnostic and therapeutic problems, such as with stage-related tumor treatment or implantable hearing aids. Diagnostic procedures, e.g., special new procedures in audiology and vestibulogy, dominated the surveys from the practices. However clinics and practices alike cited marginal areas of the discipline that are of daily relevance. DISCUSSION: The cited knowledge gaps then needed to be verified or refuted and clarified based on research of the literature as to whether the existing evidence actually reached healthcare providers in the form of guidelines, publications, conferences or continuing training for application in daily practice. Other steps would include prioritizing future research, evidence mapping, deciding on further systematic reviews, and targeted studies in conjunction with procuring third-party funding and in cooperation with patient associations. The knowledge thus gained should ultimately be transferred in improved form for application in daily clinical practice. Ten questions of key importance each needed to be formulated for the hospitals and practices.

Prevalence and spectrum of residual symptoms in Lyme neuroborreliosis after pharmacological treatment: a systematic review.

Controversy exists about residual symptoms after pharmacological treatment of Lyme neuroborreliosis. Reports of disabling long-term sequels lead to concerns in patients and health care providers. We systematically reviewed the available evidence from studies reporting treatment of Lyme neuroborreliosis to assess the prevalence and spectrum of residual symptoms after treatment. A literature search was performed in three databases and three clinical trial registers to find eligible studies reporting on residual symptoms in patients after pharmacological treatment of LNB. Diagnosis must have been performed according to consensus-derived case definitions. No restrictions regarding study design or language were set. Symptom prevalence was pooled using a random-effects model. Forty-four eligible clinical trials and studies were found: 8 RCTs, 17 cohort studies, 2 case-control studies, and 17 case series. The follow-up period in the eligible studies ranged from 7 days to 20 years. The weighted mean proportion of residual symptoms was 28 % (95 % CI 23-34 %, n = 34 studies) for the latest reported time point. Prevalence of residual symptoms was statistically significantly higher in studies using the "possible" case definition (p = 0.0048). Cranial neuropathy, pain, paresis, cognitive disturbances, headache, and fatigue were statistically significantly lower in studies using the "probable/definite" case definition. LNB patients may experience residual symptoms after treatment with a prevalence of approximately 28 %. The prevalence and spectrum of residual symptoms differ according to the applied case definition. Symptoms like fatigue are not reported in studies using the "probable/definite" case definition. As the "possible" case definition is more unspecific, patients with other conditions may be included. Reports of debilitating fatigue and cognitive impairment after LNB, a "post-Lyme syndrome", could therefore be an artifact of unspecific case definitions in single studies.

[Studies and Publication Practice in Pediatric Hematology and Oncology in Germany--An Analysis of the Period 1970-2006]. / Studien und Publikationspraxis in der PädiatrischenHämatologie und Onkologie in Deutschland--Analyseder Jahre 1970­2006.

BACKGROUND: Several therapy optimization studies (TOSs) for the treatment of hematologic and oncologic disorders in children and adolescents have been conducted in Germany. The publication of research results is necessary to ensure that future studies are well designed and based on relevant and unanswered questions. This retrospective cohort study was conducted to analyze the study- and publication practice in this field. METHODS: All study protocols in the field of the pediatric oncology and hematology in Germany were collected. Relevant data from study protocols were extracted, beginning with 1) general information about the study protocol, and 2) information about each methodological trial. In a second step, the publication practice was characterized by searching in electronic databases and by contacting principal investigators. Relevant Data of each publication was extracted. RESULTS: The research activity has increased significantly in the past few years. The found publication rate of 85% represents an outstanding publication practice. Additionally, German, as being the main publication language a few decades ago, has been almost completely replaced with English. An acceptable methodological conduct was observed in the analyzed study protocols. DISCUSSION AND CONCLUSION: Studies have been principally based on the concept of TOS, without considering a detailed breakdown into each methodological trial. A markedly subdivision of studies into methodologically identifiable trials would allow a clear definition of their parameters, while increasing transparency of the study conduct and its results.

Methodological quality of guidelines for management of Lyme neuroborreliosis.

BACKGROUND: Many aspects of clinical management of Lyme neuroborreliosis are subject to intense debates. Guidelines show considerable variability in their recommendations, leading to divergent treatment regimes. The most pronounced differences in recommendations exist between guidelines from scientific societies and from patient advocacy groups. Assessment of the methodological quality of these contradictory guideline recommendations can be helpful for healthcare professionals. METHODS: Systematic searches were conducted in MEDLINE and databases of four international and national guideline organizations for guidelines on Lyme neuroborreliosis published from 1999-2014. Characteristics (e.g., year of publication, sponsoring organization) and key recommendations were extracted from each guideline. Two independent reviewers assessed the methodological quality of each guideline according to the Appraisal of Guidelines for Research and Evaluation II (AGREE II) tool. AGREE II scores from guidelines developed by scientific societies and from patient advocacy groups were compared across domains. RESULTS: We identified eight eligible guidelines of which n = 6 were developed by scientific societies and n = 2 by patient advocacy groups. Agreement on AGREE II scores was good (Cohen's weighted kappa = 0.87, 95% CI 0.83-0.92). Three guidelines, all from scientific societies, had an overall quality score of ≥ 50%. Two of them were recommended for use according to the AGREE II criteria. Across all guidelines, the AGREE II domain with the highest scores was "Clarity of Presentation" (65, SD 19%); all other domains had scores < 50% with the domain "Applicability" having the lowest scores (4, SD 4%). Guidelines developed by scientific societies had statistically significantly higher scores regarding clarity of presentation than guidelines from patient advocacy groups (p = 0.0151). No statistically significant differences were found in other domains. CONCLUSIONS: Current guidelines on Lyme neuroborreliosis vary in methodological quality and content. Health care providers and patients need to be aware of this variability in quality when choosing recommendations for their treatment decisions regarding Lyme neuroborreliosis. No statement can be given on quality of content and validity of recommendations, as these issues are not subject to assessment with the AGREE II tool and are prone to individual interpretation of the available evidence by the corresponding guideline panels. To enhance guideline quality, guideline panels should put more emphasis on linking recommendations to the available evidence, transparency in reporting how evidence was searched for and evaluated, and the implementation of recommendations into clinical practice.

Efficacy and safety of pharmacological treatments for acute Lyme neuroborreliosis - a systematic review.

BACKGROUND AND PURPOSE: Our aim was to evaluate the available evidence for pharmacological treatment of acute Lyme neuroborreliosis as a basis for evidence-based clinical recommendations in a systematic review. METHODS: A systematic literature search of Medline, EMBASE, the Cochrane Library and three trial registries was performed. Randomized controlled trials (RCTs) and non-randomized studies (NRS) were evaluated. Risk of bias was assessed using the Cochrane risk of bias tools. The primary outcome was 'residual neurological symptoms' whilst the secondary outcomes were disability, quality of life, pain, fatigue, depression, cognition, sleep, adverse events and cerebrospinal fluid pleocytosis. The quality of the evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. RESULTS: After screening 5779 records, eight RCTs and eight NRS were included. Risk of bias was generally high. No statistically significant difference was found between doxycycline and beta-lactam antibiotics in a meta-analysis regarding residual neurological symptoms at 4-12 months [risk ratio (RR) 1.27, 95% confidence interval (CI) 0.98-1.63, P = 0.07] or adverse events (RR 0.82, 95% CI 0.54-1.25, P = 0.35). Significantly fewer neurological symptoms for cefotaxime compared with penicillin were found (RR 1.81, 95% CI 1.10-2.97, P = 0.02). Adverse events were significantly fewer for penicillin (RR 0.56, 95% CI 0.38-0.84, P = 0.005). CONCLUSIONS: Evidence regarding pharmacological treatment of acute Lyme neuroborreliosis is scarce and therefore insufficient to recommend preference of beta-lactam antibiotics over doxycycline or vice versa. However, due to considerable imprecision, relevant differences between treatments cannot be excluded. No evidence suggesting benefits of extended antibiotic treatments could be identified. Further well-designed trials are needed. Individual treatment decisions should address patients' preferences and individual conditions like prior allergic reactions.

Contributing to the growth of Physical and Rehabilitation Medicine (PRM): call for a Cochrane Field in PRM.

The European Society of Physical and Rehabilitation Medicine (ESPRM), together with the European Journal of PRM and the PRM Section and Board of the European Union of Medical Specialists (UEMS), started an action to establish a relationship with Cochrane (formerly the Cochrane Collaboration). Cochrane is a global, independent network of researchers, professionals, patients, carers and people interested in health, with contributors from more than 130 countries. Its aim is to produce credible, accessible health information that is free from any conflicts of interest. Cochrane produces the Cochrane Library, an evidence-based resource that includes today more than 6300 Cochrane systematic reviews. Cochrane is made up of many different review groups and other entities (such as Centres and Branches), distributed around the world, that are mainly focused on specific healthcare problems (diseases, or organs). Inside Cochrane also Fields have been created, that focus on a dimension of health care other than a specific healthcare problem. A Cochrane Field represents a bridge between Cochrane and the stakeholders of the related healthcare area. The medical specialty of PRM is covering a broad medical domain: it deals with function, activities and participation in a large number of health conditions, mostly but not exclusively musculoskeletal, neurological and cardiorespiratory. Consequently, the currently more than 200 existing Cochrane Reviews are scattered among different groups. A PRM Field could greatly serve to the need of the specialty, spreading the actual Cochrane knowledge, focusing needs today not covered by Cochrane Reviews, facing the intrinsic methodological problems of the specialty. This paper introduces a call for the development of a PRM Cochrane Field, briefly reviewing what Cochrane is and how it is organized, defining the value and identifying a pathway toward the development of a PRM Cochrane Field, and finally shortly reviewing the Cochrane reviews of PRM interest.

[Assessment of risk of bias in controlled studies]. / Bewertung des Risikos für Bias in kontrollierten Studien.

BACKGROUND: Practicing physicians are faced with many medical decisions daily. These are mainly influenced by personal experience but should also consider patient preferences and the scientific evidence reflected by a constantly increasing number of medical publications and guidelines. With the objective of optimal medical treatment, the concept of evidence-based medicine is founded on these three aspects. It should be considered that there is a high risk of misinterpreting evidence, leading to medical errors and adverse effects without knowledge of the methodological background. OBJECTIVES: This article explains the concept of systematic error (bias) and its importance. Causes and effects as well as methods to minimize bias are discussed. This information should impart a deeper understanding, leading to a better assessment of studies and implementation of its recommendations in daily medical practice. CONCLUSION: Developed by the Cochrane Collaboration, the risk of bias (RoB) tool is an assessment instrument for the potential of bias in controlled trials. Good handling, short processing time, high transparency of judgements and a graphical presentation of findings that is easily comprehensible are among its strengths. Attached to this article the German translation of the RoB tool is published. This should facilitate the applicability for non-experts and moreover, support evidence-based medical decision-making.

[Methods of evidence mapping. A systematic review]. / Methoden des Evidence Mappings. Eine systematische Übersichtsarbeit.

BACKGROUND: Evidence mapping is an increasingly popular approach to systematically evaluate published research. While there are methodological standards for systematic reviews, discrepancies exist between the terminology and methods used within evidence mapping. AIM: The aim of this systematic review is to describe the methodology and terminology used in evidence mapping and to demonstrate the continuum between evidence mapping and traditional systematic reviews. METHODS: A systematic literature search was conducted in 10 databases in order to obtain a comprehensive picture of the state of the research standards for evidence mapping. In addition, websites of institutions which are already conducting evidence mapping were searched. RESULTS: The included study pool (n = 12) shows that the terms 'evidence map' and 'scoping review' are widely used within evidence mapping. Evidence maps are an approach to depict both the number and characteristics of studies in tabular form that exist as well as evidence gaps based on primary studies and systematic reviews of broad clinical questions. Scoping reviews also summarize the literature in a tabular form but also give a descriptive narrative summary of the results. A quality assessment of the studies is generally not included. CONCLUSION: Evidence mapping allows the identification of research gaps. This aspect is particularly important for interventions which are used without sufficient evidence. In contrast, systematic reviews are mainly used to estimate effects for interventions and evaluate whether the included studies are reliable.

X-linked inhibitor of apoptosis (XIAP) deficiency: the spectrum of presenting manifestations beyond hemophagocytic lymphohistiocytosis.

X-linked inhibitor of apoptosis (XIAP) deficiency caused by mutations in BIRC4 was initially described in patients with X-linked lymphoproliferative syndrome (XLP) who had no mutations in SH2D1A. In the initial reports, EBV-associated hemophagocytic lymphohistiocytosis (HLH) was the predominant clinical phenotype. Among 25 symptomatic patients diagnosed with XIAP deficiency, we identified 17 patients who initially presented with manifestations other than HLH. These included Crohn-like bowel disease (n=6), severe infectious mononucleosis (n=4), isolated splenomegaly (n=3), uveitis (n=1), periodic fever (n=1), fistulating skin abscesses (n=1) and severe Giardia enteritis (n=1). Subsequent manifestations included celiac-like disease, antibody deficiency, splenomegaly and partial HLH. Screening by flow cytometry identified 14 of 17 patients in our cohort. However, neither genotype nor protein expression nor results from cell death studies were clearly associated with the clinical phenotype. Only mutation analysis can reliably identify affected patients. XIAP deficiency must be considered in a wide range of clinical presentations.

Background paper to the recommendation for routine rotavirus vaccination of infants in Germany.

Two rotavirus (RV) vaccines were introduced to the European market in 2006. To support the decision-making process of the German Standing Committee on Vaccination ("Ständige Impfkommission", STIKO) regarding adoption of routine RV vaccination into the national vaccination schedule in Germany relevant scientific background was reviewed. According to STIKO's Standard Operating Procedures for the development of evidence-based vaccination recommendations, a set of key questions was addressed and systematic reviews were performed with a focus on the efficacy, effectiveness, impact and safety of RV vaccines. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology was applied to assess the quality of available evidence. Data from 5 randomized controlled trials demonstrated a high efficacy of RV vaccines in preventing severe RV-associated gastroenteritis (91%) and hospitalization (92%) in settings comparable to Germany. Post-marketing observational studies confirmed these findings. In several countries, impact studies suggest that age groups not eligible for vaccination might also benefit from herd effects and demonstrated a decrease in the number of nosocomial RV infections after RV vaccine introduction. The vaccines were considered safe, except for a slightly increased risk of intussusception shortly after the first dose, corresponding to 1-2 additional cases per 100,000 infants vaccinated (relative risk =1.21, 95% confidence interval [CI] 0.68-2.14). RV case-fatality is extremely low in Germany. However, RV incidence among children aged <5 years is high (reported 8-14 cases per 1000 children annually), and of these almost half require hositalization. In view of the available evidence and expected benefits, STIKO recommends routine rotavirus vaccination of children under the age of 6 months with the main goal of preventing RV-associated hospitalizations in Germany, especially among infants and young children.

[Trial registration for the improvement of transparency in scientific research. The German Association of Urology now enables registration in the register network of the WHO]. / Studienregistrierung zur Verbesserung der Transparenz in der klinischen Forschung. Die DGU ermöglicht jetzt eine einfache WHO-konforme Registrierung klinischer Studien.

Transparency is essential for the efficient transfer of scientific knowledge from research into practice but is often impaired by non-publication of whole studies or by inappropriate publication of trial results. Prospective trial registration has the potential to increase transparency in scientific research because it allows the evaluation of trial methodology and the appraisal of potential publication bias. Trial registration is a scientific, ethical and moral obligation which needs self-commitment of researchers and sponsors to prospective trial registration. The urological trial register of the German Society of Urology is now affiliated with the German Register of Clinical Studies, a national primary register, which enables easy registration in the register network of the WHO.