Trials

This is a protocol for the project entitled: "Are clinical trial participants informed about potential benefits and harms? A comparison of informed consent materials and trial protocols."

BackgroundClinical trials can terminate early for many reasons, including non-scientific reasons. We aimed to develop scalable semi-automated methods to characterize terminated trials and explore a methodology to estimate the risk of experiencing serious adverse events (SAEs) in trials terminated due to non-scientific reasons. MethodsTwo cohorts of clinical trials registered in ClinicalTrials.gov were investigated: (1) a cohort of clinical trials affiliated with German university medical centre...

Background/AimsClinical trials should be designed and managed to minimise important errors with potential to compromise patient safety or data integrity, employ monitoring practices that detect and correct important errors quickly, and take robust action to prevent repetition. Regulators highlight the use of risk-based monitoring, making greater use of centralised monitoring and reducing reliance on centre visits. The TEMPER study was a prospective evaluation of triggered monitoring (a risk-base...

ObjectivesTo assess how often clinical trials exhibit primary outcome discrepancies within registry records that would not be caught by comparing results publications to the latest registry entry, but would require analysing the registration history. DesignMeta-research study. SettingAll 1746 randomised clinical trials with published results, registered in ClinicalTrials.gov or Deutsches Register Klinischer Studien (DRKS), completed at German University Medical Centres between 2009 and 2017. W...

BackgroundIdentifying and monitoring clinical trials is crucial for responsible research systems and is relevant to all stakeholders in clinical research. Trial registries support accountability and transparency by providing a publicly available and rich source of information on trials. Cross-registration, where the same trial is registered in more than one registry, can complicate efforts to study the clinical research enterprise. Duplicate entries may need to be de-duplicated or merged, and di...

BackgroundVery little is known about the practice-oriented challenges and mitigation strategies for effective and efficient translation of informed consent and study prioritization in times of a pandemic. This stakeholder interview study aimed to identify the full spectrum of challenges and mitigation strategies for informed consent and study prioritization in a pandemic setting. MethodsWe performed semi-structured interviews with German stakeholders involved in human subject research during th...

Clinical Trials Units are encouraged to integrate Patient and Public Involvement (PPI) into all aspects of trial design, delivery, oversight and dissemination. This research explored the induction and training of PPI Contributors joining trial oversight committees. It was used to create an induction pack for new PPI Contributors at the Medical Research Council Clinical Trials Unit at University College Londons (MRC CTU at UCL). We have made this resource available to all researchers and in this ...

Registration of clinical trials was introduced to mitigate the risk of publication and selective reporting bias in the realm of clinical research. The prevalence of publication and selective reporting bias in trial results has been evidenced through scientific research. This bias may compromise the ethical and methodological conduct in the design, implementation and dissemination of evidence-based healthcare interventions. Principal investigators of digital health trials may be overwhelmed with ...

Clinical trial participants who are randomized to treatment and have a baseline value but no post-baseline data pose a unique challenge. These patients need to be included to preserve randomization. However, there is no information about the outcome or the intercurrent events that led to missing data. Composite and hypothetical strategies can accommodate participants with no post-baseline data. The present study investigated common methods based on hypothetical strategies in example data sets an...

IntroductionAdverse event (AE) reporting transparency is essential for evidence-based surgical practice, yet substantial reporting gaps persist despite Consolidated Standards for Reporting Trials (CONSORT) Harms guidance. The Medical Dictionary for Regulatory Activities (MedDRA) provides standardized terminology for AE classification, but its association with AE reporting quality remains unexplored. ObjectivesThe purpose of this study was to establish the frequency of Medical Dictionary for Reg...

IntroductionHealthcare systems must use treatments that are effective and safe. Regulators licensed many currently used older medications before introducing the stringent evidential requirements imposed on modern treatments. Also, there has been little encouragement to carry out within-class, head-to-head comparisons of licensed medicines. For commonly prescribed drugs, even small differences in effectiveness or safety could have significant public health implications. However, conventional clin...

This is a protocol for the project entitled: "Are investigators access to trial data and rights to publish restricted and are trial participants informed about this? A comparison of trial protocols and informed consent materials"

Prospective registration plays an important role in ensuring the transparency and reliability of clinical trials. Preregistration of clinical trials has been required by the ICMJE since 2005 and mandated by law for most clinical trial types since 2007. It is one of the roles of peer reviewers of a clinical trial publication to confirm that there is concordance between the registry entry and the submitted publication. On October 22, 2019, abstracts for all articles indexed by PubMed with publicat...

BackgroundPublic information on US clinical trials is shared through the ClinicalTrials.gov registry. This studys goal was to determine prospective registration, results reporting, trial registration number reporting, and publication accessibility status for trials with primary completion dates from 2014 to 2017 affiliated with seven California universities. MethodsWe identified trials with investigators, sponsors, or responsible parties affiliated with seven California universities and searche...

BackgroundEmergency tracheal intubation is a common and high-risk procedure. Ketamine and etomidate are sedative medicines commonly used to induce anesthesia for emergency tracheal intubation, but whether the induction medication used affects patient outcomes is uncertain. Research QuestionDoes the use of ketamine for induction of anesthesia decrease the incidence of death among adults undergoing emergency tracheal intubation, compared to the use of etomidate? Study Design and MethodsThe Rando...

The generalizability of data derived from randomized controlled trials is of paramount importance given their utility in the Food & Drug Administration (FDA) drug approval process. An essential part of this process is the inclusion of reliably reported gender, race and ethnicity data in trials that lead to FDA drug approval. Despite previous mandates by the FDA and Clinicaltrials.gov, gender and race-specific data remains under reported. We reviewed 100 most recently approved FDA medications, an...

BackgroundExperts across industry, academia, and regulatory bodies increasingly stress the importance of prioritising participant experiences in clinical trials. Simultaneously, the shift towards decentralised approaches is reshaping how trials are designed and conducted, with a direct impact on the experiences of the participants involved. ObjectiveThis study aims to gain a deeper understanding of the experiences of participants taking part in Decentralised Clinical Trials, focusing on the uni...

BackgroundHistorically, Sweden and Denmark have excelled in clinical trial publications per million population, but many trials have remained unpublished. Enforceable policies for trial registration before launch, made global and national clinical research assessments possible. The World Health Organisation (WHO) hosts the International Clinical Trials Registry Platform (ICTRP) for interventional clinical trials, with data from 1999. ObjectiveTo find out if the retrospective or prospective tria...

Conducting systematic reviews of clinical trials is arduous and resource consuming. One potential solution is to design databases that are continuously and automatically populated with clinical trial data from harmonised and structured datasets. We aimed to map publicly available, continuously updated, topic-specific databases of randomised clinical trials (RCTs). We systematically searched PubMed, Embase, the preprint servers medRxiv, ArXiv, and Open Science Framework, and Google. We described ...

ObjectiveTo map open educational resources on how to justify, design, conduct, analyse, and share randomised clinical trials of healthcare interventions. DesignLandscape analysis. Data sourcesSystematic searches of multiple databases of biomedical literature using ASReview, a machine learning assisted systematic review tool, to screen the most relevant records. Manual searches of general websites, regulatory and clinical trial unit websites, and online learning portals. Main outcomesCategoris...