The evidence base of US Food and Drug Administration approvals of novel cancer therapies from 2000 to 2020.

Concerns have been raised that regulatory programs to accelerate approval of cancer drugs in cancer may increase uncertainty about benefits and harms for survival and quality of life (QoL). We analyzed all pivotal clinical trials and all non-pivotal randomized controlled trials (RCTs) for all cancer drugs approved for the first time by the FDA between 2000 and 2020. We report regulatory and trial characteristics.

Robustness of reported postacute health outcomes in children with SARS-CoV-2 infection: a systematic review.

Objective: To systematically assess the robustness of reported postacute SARS-CoV-2 infection health outcomes in children.

Methods: A search on PubMed and Web of Science was conducted to identify studies published up to 22 January 2022 that reported on postacute SARS-CoV-2 infection health outcomes in children (<18 years) with follow-up of ≥2 months since detection of infection or ≥1 month since recovery from acute illness. We assessed the consideration of confounding bias and causality, as well as the risk of bias.

Towards full clinical trial registration and results publication: longitudinal meta-research study in Northwestern and Central Switzerland.

Objective: The registration of clinical trials is required by law in Switzerland. We investigated (1) the proportion of registered and prospectively registered clinical trials, (2) the availability of results for ethically approved trial protocols, (3) factors associated with increased registration, and (4) reasons for non-registration.

Design And Setting: We included all clinical trials with mandatory prospective registration, which were approved by the ethics committee of Northwestern and Central Switzerland between January 1, 2016, and December 31, 2020.

A meta-research study of randomized controlled trials found infrequent and delayed availability of protocols.

Objectives: Availability of randomized controlled trial (RCT) protocols is essential for the interpretation of trial results and research transparency.

Study Design And Setting: In this study, we determined the availability of RCT protocols approved in Switzerland, Canada, Germany, and the United Kingdom in 2012. For these RCTs, we searched PubMed, Google Scholar, Scopus, and trial registries for publicly available protocols and corresponding full-text publications of results.

Reporting quality of clinical trial protocols: a repeated cross-sectional study about the Adherence to SPIrit Recommendations in Switzerland, CAnada and GErmany (ASPIRE-SCAGE).

Objectives: Comprehensive protocols are key for the planning and conduct of randomised clinical trials (RCTs). Evidence of low reporting quality of RCT protocols led to the publication of the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) checklist in 2013. We aimed to examine the quality of reporting of RCT protocols from three countries before and after the publication of the SPIRIT checklist.

Scoping review and characteristics of publicly available checklists for assessing clinical trial feasibility.

Background: Whether there is sufficient capacity and capability for the successful conduct and delivery of a clinical trial should be assessed by several stakeholders according to transparent and evidence-based criteria during trial planning. For this openly shared, user-tested, and validated tools are necessary. Therefore, we systematically examined the public availability and content of checklists which assess the study-level feasibility in the planning phase of clinical trials.

Nonregistration, discontinuation, and nonpublication of randomized trials: A repeated metaresearch analysis.

Background: We previously found that 25% of 1,017 randomized clinical trials (RCTs) approved between 2000 and 2003 were discontinued prematurely, and 44% remained unpublished at a median of 12 years follow-up. We aimed to assess a decade later (1) whether rates of completion and publication have increased; (2) the extent to which nonpublished RCTs can be identified in trial registries; and (3) the association between reporting quality of protocols and premature discontinuation or nonpublication of RCTs.

Methods And Findings: We included 326 RCT protocols approved in 2012 by research ethics committees in Switzerland, the United Kingdom, Germany, and Canada in this metaresearch study.

Investigational medicinal products, related costs and hospital pharmacy services for investigator-initiated trials: A mixed-methods study.

Background: Conducting high quality investigator-initiated trials (IITs) is challenging and costly. The costs of investigational medicinal products (IMPs) in IITs and the role of hospital pharmacies in the planning of IITs are unclear. We conducted a mixed-methods study to compare planned and actual costs of IMPs in Swiss IITs, to examine potential reasons for differences, and to gather stakeholder views about hospital services for IITs.

Effect of Anti-Inflammatory Diets on Pain in Rheumatoid Arthritis: A Systematic Review and Meta-Analysis.

Various nutritional therapies have been proposed in rheumatoid arthritis, particularly diets rich in ω-3 fatty acids, which may lead to eicosanoid reduction. Our aim was to investigate the effect of potentially anti-inflammatory diets (Mediterranean, vegetarian, vegan, ketogenic) on pain. The primary outcome was pain on a 10 cm visual analogue scale.

Treatment for gastrointestinal and pancreatic neuroendocrine tumours: a network meta-analysis.

Background: Several available therapies for neuroendocrine tumours (NETs) have demonstrated efficacy in randomised controlled trials. However, translation of these results into improved care faces several challenges, as a direct comparison of the most pertinent therapies is incomplete.

Objectives: To evaluate the safety and efficacy of therapies for NETs, to guide clinical decision-making, and to provide estimates of relative efficiency of the different treatment options (including placebo) and rank the treatments according to their efficiency based on a network meta-analysis.

Reliability of Trial Information Across Registries for Trials With Multiple Registrations: A Systematic Review.

Importance: Clinical trial registries are important for gaining an overview of ongoing research efforts and for deterring and identifying publication bias and selective outcome reporting. The reliability of the information in trial registries is uncertain.

Objective: To assess the reliability of information across registries for trials with multiple registrations.

Reporting quality of trial protocols improved for non-regulated interventions but not regulated interventions: A repeated cross-sectional study.

Objectives: To investigate the adherence of randomised controlled trial (RCT) protocols evaluating non-regulated interventions (including dietary interventions, surgical procedures, behavioural and lifestyle interventions, and exercise programmes) in comparison with regulated interventions to the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) 2013 Statement.

Methods: We conducted a repeated cross-sectional investigation in a random sample of RCT protocols approved in 2012 (n = 257) or 2016 (n = 292) by research ethics committees in Switzerland, Germany, or Canada. We investigated the proportion of accurately reported SPIRIT checklist items in protocols of trials with non-regulated as compared to regulated interventions.

Association of Convalescent Plasma Treatment With Clinical Outcomes in Patients With COVID-19: A Systematic Review and Meta-analysis.

Importance: Convalescent plasma is a proposed treatment for COVID-19.

Objective: To assess clinical outcomes with convalescent plasma treatment vs placebo or standard of care in peer-reviewed and preprint publications or press releases of randomized clinical trials (RCTs).

Data Sources: PubMed, the Cochrane COVID-19 trial registry, and the Living Overview of Evidence platform were searched until January 29, 2021.

A meta-research study revealed several challenges in obtaining placebos for investigator-initiated drug trials.

Objectives: To systematically assess the kind of placebos used in investigator-initiated randomized controlled trials (RCTs), from where they are obtained, and the hurdles that exist in obtaining them.

Study Design And Setting: PubMed was searched for recently published noncommercial, placebo-controlled randomized drug trials. Corresponding authors were invited to participate in an online survey.

Rationale and design of repeated cross-sectional studies to evaluate the reporting quality of trial protocols: the Adherence to SPIrit REcommendations (ASPIRE) study and associated projects.

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.

Prediction of RECRUITment In randomized clinical Trials (RECRUIT-IT)-rationale and design for an international collaborative study.

Background: Poor recruitment of patients is the predominant reason for early termination of randomized clinical trials (RCTs). Systematic empirical investigations and validation studies of existing recruitment models, however, are lacking. We aim to provide evidence-based guidance on how to predict and monitor recruitment of patients into RCTs.

Uncertainties about the need for ethics approval in Switzerland: a mixed-methods study.

Background: To ensure ethical oversight, researchers wanting to conduct “research” involving human beings are typically required to obtain prior approval from an independent ethics committee. However, it can sometimes be unclear if a project needs to be submitted for ethics approval. Swiss researchers can contact research ethics committees via a “jurisdictional inquiry” for clarification whether a project needs to be submitted for ethics approval.

Obtaining and managing data sets for individual participant data meta-analysis: scoping review and practical guide.

Background: Shifts in data sharing policy have increased researchers' access to individual participant data (IPD) from clinical studies. Simultaneously the number of IPD meta-analyses (IPDMAs) is increasing. However, rates of data retrieval have not improved.

Comparison of randomized controlled trials discontinued or revised for poor recruitment and completed trials with the same research question: a matched qualitative study.

Background: More than a quarter of randomized controlled trials (RCTs) are prematurely discontinued, mostly due to poor recruitment of patients. In this study, we systematically compared RCTs discontinued or revised for poor recruitment and completed RCTs with the same underlying research question to better understand the causes of poor recruitment, particularly related to methodological aspects and context-specific study settings.

Methods: We compared RCTs that were discontinued or revised for poor recruitment to RCTs that were completed as planned, matching in terms of population and intervention.

A scoping review shows that several nonvalidated budget planning tools for randomized trials are available.

Objectives: We aimed to provide a systematic overview of freely available tools which may help plan or monitor costs for randomized clinical trials (RCTs).

Study Design And Setting: We systematically searched MEDLINE, EMBASE, and EconLit and conducted internet searches via Google (last search, October 2018). We included all freely available tools and determined their specific purpose, which parts of clinical trial projects and which types of costs they covered, and if they were user-tested or validated in any form.

Acetylcholinesterase inhibitors combined with memantine for moderate to severe Alzheimer's disease: a meta-analysis.

Background: The clinical efficacy and safety of combination therapy with acetylcholinesterase inhibitor (AChEI) and memantine compared to AChEI or memantine alone in patients with Alzheimer’s disease is inconclusive.

Aims Of The Study: We conducted a systematic review and meta-analysis of randomised controlled trials (RCTs) comparing the clinical efficacy and safety of combination therapy of AChEI and memantine to monotherapy with either substance in patients with moderate to severe Alzheimer's disease (Mini-Mental State Examination score is <20).

Methods: We systematically searched EMBASE, Medline and CENTRAL until February 2018 for eligible RCTs.

Reporting Quality of Journal Abstracts for Surgical Randomized Controlled Trials Before and After the Implementation of the CONSORT Extension for Abstracts.

Background: Adequate reporting is crucial in full-text publications but even more so in abstracts because they are the most frequently read part of a publication. In 2008, an extension for abstracts of the Consolidated Standards of Reporting Trials (CONSORT-A) statement was published, defining which items should be reported in abstracts of randomized controlled trials (RCTs). Therefore, we compared the adherence of RCT abstracts to CONSORT-A before and after the publication of CONSORT-A.

Therapeutic Options for Neuroendocrine Tumors: A Systematic Review and Network Meta-analysis.

Importance: Multiple therapies are currently available for patients with neuroendocrine tumors (NETs), yet many therapies have not been compared head-to-head within randomized clinical trials (RCTs).

Objective: To assess the relative safety and efficacy of therapies for NETs.

Data Sources: PubMed, Embase, the Cochrane Central Register of Controlled Trials, trial registries, meeting abstracts, and reference lists from January 1, 1947, to March 2, 2018, were searched.