Matthias Briel

Universitätsspital Basel · Institute for Clinical Epidemiology and Biostatistics (CEB)

Background After basic immunization with 2 mRNA SARS-CoV-2 vaccine doses, only a small proportion of patients who are severely immunocompromised generate a sufficient antibody response. Hence, we assessed the additional benefit of a third SARS-CoV-2 vaccine in patients with different levels of immunosuppression. Methods In this observational exten...

Performing a systematic search of a methods topic (e.g., "risk of bias”, "subgroup analysis") in biomedical databases such as MEDLINE or Embase can be challenging. In this commentary, we address common search-related challenges, including inconsistent terminology for methods and suboptimal indexing. We suggest that reviewers addressing methods topi...

Background Type 2 diabetes (T2D) poses a growing public health burden, especially in low- and middle-income countries (LMICs). Task-shifting to lay village health workers (VHWs) and the use of digital clinical decision support systems (CDSS) are promising approaches to tackle the current T2D care gap in LMICs. However, evidence on the effectiveness...

Objectives This study aimed to investigate the association of demographic and clinical characteristics, including HIV-specific parameters with the antibody response to a third dose of a SARS-CoV-2 mRNA vaccine in people living with HIV-1 (PWH). Design Post-hoc analysis of data collected during the observational extension of the COrona VaccinE tRiA...

Background: Corticosteroids could improve outcomes in patients with community-acquired pneumonia (CAP). However, we hypothesize that corticosteroid effectiveness varies among individual patients, resulting in inconsistent outcomes and unclear clinical indication. Therefore, we developed and validated a predictive, causal model based on baseline cha...

Background Type 2 diabetes (T2D) poses a growing public health burden, especially in low- and middle-income countries (LMICs). Task-shifting to lay village health workers (VHWs) and the use of digital clinical decision support systems (CDSS) are promising approaches to tackle the current T2D care gap in LMICs. However, evidence on the effectiveness...

Introduction Although interest in including non-randomised studies of interventions (NRSIs) in meta-analysis of randomised controlled trials (RCTs) is growing, estimates of effectiveness obtained from NRSIs are vulnerable to greater bias than RCTs. The objectives of this study are to: (1) explore how NRSIs can be integrated into a meta-analysis of...

Importance: Numerous studies have shown that adherence to reporting guidelines is suboptimal. Objective: To evaluate whether asking peer reviewers to check if specific reporting guideline items were adequately reported would improve adherence to reporting guidelines in published articles. Design, setting, and participants: Two parallel-group,...

Background Most randomized controlled trials (RCTs) in the academic setting have limited resources for clinical trial management and monitoring. Inefficient conduct of trials was identified as an important source of waste even in well-designed studies. Thoroughly identifying trial-specific risks to enable focussing of monitoring and management effo...

Extension of the COVERALL randomised trial showed non-inferiority in antibody response of the third dose of Moderna mRNA-1273 vaccine (95.3%; 95% confidence interval [CI]: 91.9-98.7%) compared to Pfizer-BioNTech BNT162b2 vaccine (98.1%; 95% CI: 95.9-100.0%) in individuals with different levels of immunosuppression (difference: -2.8%; 95% CI: -6.8-1...

Objectives: To update previous GRADE guidance addressing inconsistency and interpreting subgroup analyses. Study design and setting: Using an iterative process, we consulted with members of the GRADE working group through multiple rounds of written feedback and discussions at GRADE working group meetings. Results: The guidance complements prev...

Background: Interpretation of the evidence from randomised controlled trials (RCTs) of remdesivir in patients treated in hospital for COVID-19 is conflicting. We aimed to assess the benefits and harms of remdesivir compared with placebo or usual care in these patients, and whether treatment effects differed between prespecified patient subgroups....

Importance: Improving methodological quality is a priority in the health research community. Finding appropriate methods guidance can be challenging due to heterogeneous terminology, poor indexing in medical databases, and variation in formats. The Library of Guidance for Health Scientists (LIGHTS) is a new searchable database for methods guidance...

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...

Background Baricitinib has shown efficacy in hospitalized patients with COVID-19, but no placebo-controlled trials have focused specifically on severe/critical COVID, including vaccinated participants. Methods Bari-SolidAct is a phase-3, multicentre, randomised, double-blind, placebo-controlled trial, enrolling participants from June 3, 2021 to Ma...

Background HRQoL is an indicator of individuals’ perception of their overall health, including social and environmental aspects. As a multidimensional concept, HRQoL can be influenced by a multitude of factors. Studies of HRQoL and factors associated with it among home-dwelling older adults have often been limited to inpatient settings or to a sub-...

Background: Evaluations of integrated care models for home-dwelling frail older adults have shown inconclusive results on health and service outcomes. However, limited research has focused on the implementation of integrated care models. Applying implementation science methods may facilitate uptake of integrated care models, thus generating positi...

Methodische Probleme (z.B. Umgang mit fehlenden Daten, irrelevante Endpunkte, fehlerhafte Subgruppenanalysen) begrenzen häufig den wissenschaftlichen Wert von klinischen Studien. Zu den Versäumnissen trägt bei, dass Gesundheitsforschende relevante Methodenleitlinien nicht finden können. Um die Auffindbarkeit von Methodenleitlinien zu verbessern, ha...

This work aims to assess the performance of two post-arrest (out-of-hospital cardiac arrest, OHCA, and cardiac arrest hospital prognosis, CAHP) and one pre-arrest (good outcome following attempted resuscitation, GO-FAR) prediction model for the prognostication of neurological outcome after cardiac arrest in a systematic review and meta-analysis. A...

Background The rapid course of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic calls for fast implementation of clinical trials to assess the effects of new treatment and prophylactic interventions. Building trial platforms embedded in existing data infrastructures is an ideal way to address such questions within well-defi...

Background Home-dwelling frail older adults are often faced with multimorbidity and complex care needs, requiring health and social care systems that support frail older adults to age in place. The objective of this paper was to investigate the types of formal health and social care as well as informal care and social support used by home-dwelling...

Objective To establish whether items included in instruments published in the last decade assessing risk of bias of randomized controlled trials (RCTs) are indeed addressing risk of bias. Study Design and Setting We searched Medline, Embase, Web of Science, and Scopus from 2010 to October 2021 for instruments assessing risk of bias or methodologic...

Background Most randomized controlled trials (RCTs) in the academic setting have limited resources for clinical trial management and monitoring. Inefficient conduct of trials was identified as an important source of waste even in well-designed studies. A comprehensive approach identifying and continuously checking critical trial risks (e.g. insuffi...

We identified determinants of SARS-CoV-2 mRNA vaccine antibody response in people with HIV (PWH). Antibody response was higher among PWH less than 60 years, with CD4+ cell count superior to 350 cells/μl and vaccinated with mRNA-1273 by Moderna compared with BNT162b2 by Pfizer-BioNTech. Preinfection with SARS-CoV-2 boosted the antibody response and...

Background To assess the quality of reporting of RCT protocols approved by UK research ethics committees before and after the publication of the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) guideline. Methods We had access to RCT study protocols that received ethical approval in the UK in 2012 (n=103) and 2016 (n=108...

Objective This systematic review aimed to identify the characteristics and application of citation analyses in evaluating the justification, design, and placement of the research results of clinical health studies in the context of earlier, similar studies. Study Design We searched MEDLINE (OVID), Embase (OVID), and the Cochrane Methodology Regist...

Objective: The registration of clinical trials is required by law in Switzerland. We investigated (1) the proportion of pro- and retrospectively 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 Sett...

Research on research (RoR), or meta-research, is the study of research itself. In 2019, a group of meta-researchers and members of the SCTO’s Clinical Trial Unit Network interested in meta-research founded the Swiss clinical Trials Empirical Assessment & Methods (STEAM) working group to promote RoR in Switzerland. Specifically, STEAM aims to contin...

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 examine...

Objective To assess the current practice of developing and presenting methods guidance and explore opportunities for improvement. Study Design and Setting We systematically surveyed methods guidance published in high-impact general and methodology-focused medical journals indexed in MEDLINE in 2020. We included articles that explicitly stated the...

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 fr...

Objective 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 UK in 2012. For these RCTs, we searched PubMed, Google Scholar...

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...

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...

Background: BNT162b2 by Pfizer-BioNTech and mRNA-1273 by Moderna are the most commonly used vaccines to prevent SARS-CoV-2 infections. Head-to-head comparison of the efficacy of these vaccines in immunocompromised patients is lacking. Methods: Parallel, two-arm (allocation 1:1), open-label, non-inferiority randomised clinical trial nested into t...

We aimed at systematically assessing the characteristics and quality of current methodology guidelines. We performed a systematic review of methodology guidelines published in the most influential medical journals in 2020. We included all articles that provided explicit methodology guidance for health researchers.

Objectives: When a randomized clinical trial (RCT) prematurely discontinues, it is essential that stakeholders do the right thing to ensure that lessons can be learnt and trust in clinical research is maintained. There is, however, a lack of evidence exploring this issue. This study aimed to examine clinical trial stakeholders´ practices following...

Background: Trial monitoring is an important component of good clinical practice to ensure the safety and rights of study participants, confidentiality of personal information, and quality of data. However, the effectiveness of various existing monitoring approaches is unclear. Information to guide the choice of monitoring methods in clinical inter...

Importance A systematic assessment of existing research should justify the conduct and inform the design of new clinical research but is often lacking. There is little research on the barriers to and factors facilitating systematic evidence assessments. Objective To examine the practices and attitudes of Swiss stakeholders and international funder...

Background Poor participant recruitment is the most frequent reason for premature discontinuation of randomized clinical trials (RCTs), particularly if they are investigator-initiated. The aims of this qualitative study were to investigate (1) the views of clinical trial stakeholders from three different countries regarding reasons for recruitment...

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...

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...

This cross-sectional study compares randomized clinical trial protocols to assess the prevalence and reporting quality of planned subgroup analyses over time.

Background Late 2019, a new highly contagious coronavirus SARS-CoV-2 has emerged in Wuhan, China, causing within 2 months a pandemic with the highest disease burden in elderly and people with pre-existing medical conditions. The pandemic has highlighted that new and more flexible clinical trial approaches, such as trial platforms, are needed to ass...

Background: In 2020, the COVID-19 pandemic led to an unprecedented volume of almost 3,000 clinical trials registered worldwide. We aimed to describe the COVID-19 clinical trial research agenda in Germany during the first year of the pandemic. Methods: We identified randomized clinical trials assessing interventions to treat or prevent COVID-19 that...

Background Most older adults prefer to continue living at home despite increasing care needs and demand for services. To aid in maintaining independence, integrated care models for community-dwelling older people are promoted as the most cost-effective approach. The implementation of such care models is challenging and often the end-users are not i...

Objective: Benefit or harm of higher positive end expiratory pressure (PEEP) for acute respiratory distress syndrome (ARDS) is controversial. We aimed to assess the impact of higher levels of PEEP in patients with ARDS under a Bayesian framework. Design: Systematic review and Bayesian meta-analysis of randomised clinical trials comparing higher to...

Importance Randomized clinical trials (RCTs) are an essential method of evaluating health care interventions and a cornerstone for evidence-based health care. However, RCTs have become increasingly complex and costly, which is particularly challenging for independent investigator-initiated clinical trials (IICTs). IICTs have an essential role in cl...

Glucocorticoids are frequently prescribed in inflammatory diseases and have recently experienced a boom in the treatment of COVID‐19. Small studies have shown an effect of glucocorticoids on inflammatory marker levels, but definitive proof is lacking. We investigated the influence of prednisone on inflammatory biomarkers in a previous placebo‐contr...

Background Older patients have a less pronounced immune response to infection, which may also influence infection biomarkers. There is currently insufficient data regarding clinical effects of procalcitonin (PCT) to guide antibiotic treatment in older patients. Objective and design We performed an individual patient data meta-analysis to investiga...

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 Interv...

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...

Importance: In many health systems, access to off-label drug use is controlled through reimbursement restrictions by health insurers, especially for expensive cancer drugs. Objective: To determine whether evidence from randomized clinical trials is associated with reimbursement decisions for requested off-label use of anticancer drugs in the Swi...

Introduction: Methodological studies (ie, studies that evaluate the design, conduct, analysis or reporting of other studies in health research) address various facets of health research including, for instance, data collection techniques, differences in approaches to analyses, reporting quality, adherence to guidelines or publication bias. As a res...

In health research, statistical methods are frequently used to address a wide variety of research questions. For almost every analytical challenge, different methods are available. But how do we choose between different methods and how do we judge whether the chosen method is appropriate for our specific study? Like in any science, in statistics, e...

Importance Clinical trial evidence used to support drug approval is typically the only information on benefits and harms that patients and clinicians can use for decision-making when novel cancer therapies become available. Various evaluations have raised concern about the uncertainty surrounding these data, and a systematic investigation of the av...

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 stakeho...

Background: Study-level meta-analyses provide high-certainty evidence that heparin reduces the risk of symptomatic venous thromboembolism for patients with cancer; however, whether the benefits and harms associated with heparin differ by cancer type is unclear. This individual participant data meta-analysis of randomised controlled trials examines...

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. Ou...

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 “...