Abstract: Background Study publication bias and outcome reporting bias have been recognised as two threats to the validity of systematic reviews. The purpose of this research was to estimate the proportion of missing participant outcome data from randomised controlled trials (RCTs) due to lack of publication of whole studies and due to outcome data missing within study publications. Methods and Findings Data were extracted from protocols of clinical research projects submitted to the research ethics committee of the University of Freiburg (Germany) between 2000 and 2002 and associated fully published articles. The total amount of published and unpublished outcome data from all trial participants was calculated for each trial and the overall proportion of missing data from both unpublished and published trials computed. Full and partially reported outcome data was also taken into consideration. The impact of funding source on missingness was also considered at the trial level. From 308 parallel group trials in the study cohort, 167 were published and 141 were unpublished. Overall, 260,563 participants contributed to a total of 2,618,116 participant outcome data across all trials. About half (47%) of the participant outcome data from the 308 trials was reported in full but at least 81% were partially reported. Of the 19% of participant data that were missing, 4% was attributable to missing data from published trials and 15% from unpublished trials. Commercially funded trials had a higher probability of publication (relative risk 1.20, 95% confidence interval 0.86, 1.67; p = 0.27) but were less likely to fully report all outcomes than non-commercially funded trials (relative risk 0.64, 95% confidence interval 0.30, 1.38; p = 0.26). Conclusions Missing participant outcome data from both published and unpublished trials is frequent. Clinical trial registration including outcome information not only identifies that clinical trials exist but the systematic examination and monitoring of trial information within a registry can help detect selective reporting of entire studies and of outcome data within studies and possibly prevent it

Abstract: Background Clearly structured and comprehensive protocols are an essential component to ensure safety of participants, data validity, successful conduct, and credibility of results of randomized clinical trials (RCTs). Funding agencies, research ethics committees (RECs), regulatory agencies, medical journals, systematic reviewers, and other stakeholders rely on protocols to appraise the conduct and reporting of RCTs. In response to evidence of poor protocol quality, the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) guideline was published in 2013 to improve the accuracy and completeness of clinical trial protocols. The impact of these recommendations on protocol completeness and associations between protocol completeness and successful RCT conduct and publication remain uncertain. Objectives and methods Aims of the Adherence to SPIrit REcommendations (ASPIRE) study are to investigate adherence to SPIRIT checklist items of RCT protocols approved by RECs in the UK, Switzerland, Germany, and Canada before (2012) and after (2016) the publication of the SPIRIT guidelines; determine protocol features associated with non-adherence to SPIRIT checklist items; and assess potential differences in adherence across countries. We assembled an international cohort of RCTs based on 450 protocols approved in 2012 and 402 protocols approved in 2016 by RECs in Switzerland, the UK, Germany, and Canada. We will extract data on RCT characteristics and adherence to SPIRIT for all included protocols. We will use multivariable regression models to investigate temporal changes in SPIRIT adherence, differences across countries, and associations between SPIRIT adherence of protocols with RCT registration, completion, and publication of results. We plan substudies to examine the registration, premature discontinuation, and non-publication of RCTs; the use of patient-reported outcomes in RCT protocols; SPIRIT adherence of RCT protocols with non-regulated interventions; the planning of RCT subgroup analyses; and the use of routinely collected data for RCTs. Discussion The ASPIRE study and associated substudies will provide important information on the impact of measures to improve the reporting of RCT protocols and on multiple aspects of RCT design, trial registration, premature discontinuation, and non-publication of RCTs observing potential changes over time

Abstract: Background: Clinicians around the world perform clinical research in addition to their high workload. To meet the demands of high quality Investigator Initiated Trials (IITs), Clinical Trial Units (CTUs) (as part of Academic Research Institutions) are implemented worldwide. CTUs increasingly hold a key position in facilitating the international mutual acceptance of clinical research data by promoting clinical research practices and infrastructure according to international standards. Aim: In this project, we aimed to identify services that established and internationally operating CTUs - members of the International Clinical Trial Center Network (ICN) - consider most important to ensure the smooth processing of a clinical trial while meeting international standards. We thereby aim to drive international harmonization by providing emerging and growing CTUs with a resource for informed service range set-up. Methods: Following the AMEE Guide, we developed a questionnaire, addressing the perceived importance of different CTU services. Survey participants were senior representatives of CTUs and part of the ICN with long-term experience in their field and institution. Results: Services concerning quality and coordination of a research project were considered to be most essential, i.e., Quality management, Monitoring and Project management, followed by Regulatory & Legal affairs, Education & Training, and Data management. Operative services for conducting a research project, i.e., Study Nurse with patient contact and Study Nurse without patient contact, were considered to be least important. Conclusion: To balance the range of services offered while meeting high international standards of clinical research, emerging CTUs should focus on offering (quality) management services and expertise in regulatory and legal affairs. Additionally, education and training services are required to ensure clinicians are well trained on GCP and legislation. CTUs should evaluate whether the expertise and resources are available to offer operative services

Abstract: Background Little is known about publication agreements between industry and academic investigators in trial protocols and the consistency of these agreements with corresponding statements in publications. We aimed to investigate (i) the existence and types of publication agreements in trial protocols, (ii) the completeness and consistency of the reporting of these agreements in subsequent publications, and (iii) the frequency of co-authorship by industry employees. Methods and Findings We used a retrospective cohort of randomized clinical trials (RCTs) based on archived protocols approved by six research ethics committees between 13 January 2000 and 25 November 2003. Only RCTs with industry involvement were eligible. We investigated the documentation of publication agreements in RCT protocols and statements in corresponding journal publications. Of 647 eligible RCT protocols, 456 (70.5%) mentioned an agreement regarding publication of results. Of these 456, 393 (86.2%) documented an industry partner's right to disapprove or at least review proposed manuscripts; 39 (8.6%) agreements were without constraints of publication. The remaining 24 (5.3%) protocols referred to separate agreement documents not accessible to us. Of those 432 protocols with an accessible publication agreement, 268 (62.0%) trials were published. Most agreements documented in the protocol were not reported in the subsequent publication (197/268 [73.5%]). Of 71 agreements reported in publications, 52 (73.2%) were concordant with those documented in the protocol. In 14 of 37 (37.8%) publications in which statements suggested unrestricted publication rights, at least one co-author was an industry employee. In 25 protocol-publication pairs, author statements in publications suggested no constraints, but 18 corresponding protocols documented restricting agreements. Conclusions Publication agreements constraining academic authors' independence are common. Journal articles seldom report on publication agreements, and, if they do, statements can be discrepant with the trial protocol

Zusammenfassung: The 'Manual Systematic Literature Search for the Development of Guidelines" adresses the needs of guideline developers and authors regarding an efficient and qualified literature search to identify all the available evidence relevant for the medical topic. The Manual can stand alone or could be used to train authors and developers for independent literature searches. It is based on international accepted standards for the conduct of systematic literature searches. It is complementary to the standards for guideline development of the German Association of the Scientific Medical Societies

Abstract: Das "Manual Systematische Recherche für Evidenzsynthesen und Leitlinien" richtet sich vor allem an Leitlinien-Ersteller und Leitlinien-Berater mit dem Ziel, sie über eine qualifizierte Recherche zu informieren und bei gegebener praktischer Anleitung (z. B. im Rahmen eines Leitlinien-Seminars) zu einer eigenständigen Recherche zu befähigen. Die Grundlagen dieses Manuals bilden international anerkannte Standards für die Durchführung von Recherchen. Das Manual ergänzt und vertieft das AWMF-Regelwerk zur Erstellung von Leitlinien, im Besonderen die Kapitel "Planung und Organisation" und "Leitlinien-Entwicklung" mit den Abschnitten "Formulierung von klinisch relevanten Fragestellungen", "Systematische Evidenzbasierung", "Recherche, Auswahl und methodische Bewertung bereits vorhandener Leitlinien und deren Aufbereitung" sowie "Recherche, Auswahl und methodische Bewertung von Literatur und deren Aufbereitung"