Lars G Hemkens

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

Vaccines are vital to control the Coronavirus disease 2019 (COVID-19) pandemic, but the pressure to quickly move from research to implementation in the context of a pandemic crisis raises concerns about benefits and harms, vaccine acceptance and fair access. Here we present a strategy for the COVID-19 vaccination rollout which can be rapidly embedd...

Objective To compare effect estimates of randomised clinical trials that use routinely collected data (RCD-RCT) for outcome ascertainment with traditional trials not using routinely collected data. Design Meta-research study. Data source Studies included in the same meta-analysis in a Cochrane review. Eligibility criteria for study selection Ran...

Background: Many technology companies, including Airbnb, Amazon, Booking.com, eBay, Facebook, Google, LinkedIn, Lyft, Microsoft, Netflix, Twitter, Uber, and Yahoo!/Oath, run online randomized controlled experiments at scale, namely hundreds of concurrent controlled experiments on millions of users each, commonly referred to as A/B tests. Originall...

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 Ov...

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 clinica...

Objective To investigate the longitudinal dynamics of serum glial fibrillary acidic protein (sGFAP) and serum neurofilament light chain (sNfL) levels in people with multiple sclerosis (pwMS) under B‐cell depleting therapy (BCDT) and their capacity to prognosticate future progression independent of relapse activity (PIRA) events. Methods A total of...

Background Treatment decisions for persons with relapsing–remitting multiple sclerosis (RRMS) rely on clinical and radiological disease activity, the benefit-harm profile of drug therapy, and preferences of patients and physicians. However, there is limited evidence to support evidence-based personalized decision-making on how to adapt disease-modi...

Routinely collected health data (RCD) including electronic health records, disease registries, health administrative data and wearables data are not specifically collected for research purposes. Analysis of these data poses unique methodological challenges that must be addressed when conducting research, particularly as availability and use increas...

Background Immunotherapies for cancers are being tested in large numbers of clinical trials. It is nearly impossible for clinicians and researchers to stay current with the evidence, and traditional systematic reviews and clinical guidelines are not suited to ensure a continued overview of all trials and their results. To address this problem, we h...

Background: It is unknown whether large language models (LLMs) may facilitate time- and resource-intensive text-related processes in evidence appraisal. Objectives: To quantify the agreement of LLMs with human consensus in appraisal of scientific reporting (PRISMA) and methodological rigor (AMSTAR) of systematic reviews and design of clinical trial...

Background Increasingly, patients, clinicians, and regulators call for more evidence on the impact of innovative medicines on quality of life (QoL). We assessed the effects of disease-modifying therapies (DMTs) on QoL in people with multiple sclerosis (PwMS). Methods Randomized trials assessing approved DMTs in PwMS with results for at least one o...

Background: Technological devices such as smartphones, wearables and virtual assistants enable health data collection, serving as digital alternatives to conventional biomarkers. We aimed to provide a systematic overview of emerging literature on ‘digital biomarkers,’ covering definitions, features and citations in biomedical research. Methods: We...

In medical research as a whole, frequent inaccurate or biased findings are of international concern. One measure against reporting biases is study registration before the start of data collection (preregistration), preferably together with the statistical analysis plan. This meta-research study systematically evaluated registration of Swedish obser...

Background Treatment decisions for persons with relapsing-remitting multiple sclerosis (RRMS) rely on clinical and radiological disease activity, the benefit-harm profile of drug therapy, and preferences of patients and physicians. However, there is limited evidence to support evidence-based personalized decision-making on how to adapt disease modi...

Introduction Cohort studies generate and collect longitudinal data for a variety of research purposes. Randomised controlled trials (RCTs) increasingly use cohort studies as data infrastructures to help identify and recruit trial participants and assess outcomes. Objective To examine the extent, range and nature of research using cohorts for RCTs...

Introduction: Up to one fifth of breast cancer survivors will develop chronic breast cancer-related lymphedema (BCRL). To date complex physical decongestion therapy (CDT) is the gold standard of treatment. However, it is mainly symptomatic and often ineffective in preventing BCRL progression. Lymphovenous anastomosis (LVA) and vascularized lymph no...

Objective: To systematically evaluate timely reporting of clinical trial results at medical universities and university hospitals in the Nordic countries. Study Design and Setting: In this cross-sectional study, we included trials (regardless of intervention) registered in the EU Clinical Trials Registry and/or ClinicalTrials.gov, completed 2016-20...

Background Technological devices such as smartphones, wearables, sensors, or virtual assistants allow to collect data on health and disease processes and are thus increasingly considered a useful digital alternative to conventional biomarkers. We aimed to provide a systematic overview of the emerging literature on "digital biomarkers" with their de...

Background Pragmatic trials provide decision-oriented, real-world evidence that is highly applicable and generalizable. The interest in real-world evidence is fueled by the assumption that effects in the “real-world” are different to effects obtained under artificial, controlled, research conditions as often used for traditional explanatory trials....

Objective: To quantify the strength of statistical evidence of randomised controlled trials (RCTs) for novel cancer drugs approved by the Food and Drug Administration (FDA) in the last two decades. Methods: We used data on overall survival (OS), progression-free survival (PFS), and tumour response (TR) for novel cancer drugs approved for the first...

Background Cigarette smoking is the leading preventable cause of premature death. Despite dedicated programmes, quit rates remain low due to barriers such as nicotine withdrawal syndrome or post-cessation weight gain. Glucagon-like peptide-1 (GLP-1) analogues reduce energy intake and body weight and seem to modulate addictive behaviour. These GLP-1...

Background Pragmatic trials provide decision-oriented, real-world evidence that is highly applicable and generalizable. The interest in real world evidence is fueled by the assumption that effects in the “real-world” are different to effects obtained under artificial, controlled, research conditions as often used for traditional explanatory trials....

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 betw...

Background: We have followed the COVID-19 clinical trial research agenda from the beginning using the COVID-evidence.org platform. Now, two years after the COVID-19 pandemic started, our aim was to re-examine this research agenda with the latest data to provide a global perspective on the research landscape with a focus on Germany. Methods: We r...

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...

Objectives To determine the prevalence and predictors of subclinical giant cell arteritis (GCA) in patients with newly diagnosed polymyalgia rheumatica (PMR). Methods PubMed, Embase, and Web of Science Core Collection were systematically searched (date of last search July 14, 2021) for any published information on any consecutively recruited cohor...

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...

Objective To describe the characteristics and the survival of patients with cancer with intended off-label use (OLU) cancer treatment and reimbursement request. Design Cohort study using medical record data. Setting Three major cancer centres in Switzerland. Participants 519 patients with cancer and a reimbursement request for OLU between Januar...

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 Assessing changes in coverage, recall, review conclusions and references not found when searching fewer databases. Study design and setting In 60 randomly selected Cochrane reviews, we checked included study publications' coverage (indexation) and recall (findability) using different search approaches with MEDLINE, Embase, and CENTRAL an...

Objectives: To determine the prevalence and predictors of subclinical giant cell arteritis (GCA) in patients with newly diagnosed polymyalgia rheumatica (PMR). Methods: PubMed, Embase, and Web of Science Core Collection were systematically searched (date of last search July 14, 2021) for any published information on any consecutively recruited coh...

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 c...

Blog entry written on: Randomized trials on non-pharmaceutical interventions for COVID-19: a scoping review, (bmjebm-2021-111825)

Importance There is concern that post-acute SARS-CoV-2 infection health outcomes (“post-COVID syndrome”) in children could be a serious problem but at the same time there is concern about the validity of reported associations between infection and long-term outcomes. Objective To systematically assess the validity of reported post-acute SARS-CoV-2...

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.

Objective: We aimed at providing a systematic overview of randomised trials assessing non-pharmaceutical interventions (NPIs) to prevent COVID-19. Design: Scoping review. Methods: We included all randomised trials assessing NPIs to prevent COVID-19 in any country and setting registered in ClinicalTrials.gov and the WHO International Clinical Tria...

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...

This paper aims to provide early-career researchers with a useful introduction to good research practices.

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...

Zusammenfassung Digitale Gesundheitsanwendungen (DiGA) versprechen, die Gesundheit und medizinische Versorgung von Patienten zu verbessern. Dieser Beitrag gibt eine kurze Übersicht zur evidenzbasierten Nutzenbewertung und den Herausforderungen an die zugrunde liegende Evidenz als Voraussetzungen für eine optimale, patientenorientierte Entscheidungs...

Objective: We evaluated reporting completeness and transparency in randomised controlled trials (RCTs) conducted using administrative data based on 2021 CONSORT Extension for Trials Conducted Using Cohorts and Routinely Collected Data (CONSORT-ROUTINE) criteria. Study design and setting: MEDLINE and the Cochrane Methodology Register were searche...

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...

Introduction: The emphasis on aesthetic outcomes and quality of life (QoL) has motivated surgeons to develop skin-sparing or nipple-sparing mastectomy (SSM/ NSM) for breast cancer treatment or prevention. During the same operation, a so-called immediate breast reconstruction is performed. The breast can be reconstructed by positioning of a breast...

Objective To describe characteristics of randomised controlled trials (RCTs) conducted using electronic health records (EHRs), including completeness and transparency of reporting assessed against the 2021 CONSORT Extension for RCTs Conducted Using Cohorts and Routinely Collected Data (CONSORT-ROUTINE) criteria. Study design MEDLINE and Cochrane M...

Background: Numerous non-pharmaceutical interventions (NPIs) were taken worldwide to contain the spread of the COVID-19 pandemic. We aimed at providing an overview of randomized trials assessing NPIs to prevent COVID-19. Methods: We included all randomized trials assessing NPIs to prevent COVID-19 in any country and setting registered in ClinicalTr...

Background: Protocols are an essential document for conducting randomised controlled trials (RCTs). However, the completeness of the information provided is often inadequate. To help improve the content of trial protocols, an international group of stakeholders published the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT...

BACKGROUND:Protocols are an essential document for conducting randomised controlled trials (RCTs). However, the completeness of the information provided is often inadequate. To help improve the content of trial protocols, an international group of stakeholders published the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT)...

Background GCA is characterized by cranial symptoms but imaging techniques show that patients with non-specific symptoms such as systemic inflammation or PMR may have undiagnosed large vessel (LV) GCA ¹ . Although silent GCA in patients with clinically isolated PMR may have consequences for patients’ outcome, little is known about its prevalence an...

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...

The COVID-19 crisis led to a flurry of clinical trials activity. The COVID-Evidence database shows 2,814 COVID-19 randomized trials registered as of February 16, 2021. Most were small (only 18% have a planned sample size >500) and the rare completed ones have not provided published results promptly (only 283 trial publications as of 2/2021). Small...

Randomised controlled trials are increasingly conducted as embedded, nested, or using cohorts or routinely collected data, including registries, electronic health records, and administrative databases, to assess if participants are eligible for the trial and to facilitate recruitment, to deliver an embedded intervention, to collect trial outcome da...

Substantial COVID-19 research investment has been allocated to randomized clinical trials (RCTs) on hydroxychloroquine/chloroquine, which currently face recruitment challenges or early discontinuation. We aim to estimate the effects of hydroxychloroquine and chloroquine on survival in COVID-19 from all currently available RCT evidence, published an...

Objectives Randomised controlled trials conducted using cohorts and routinely collected data, including registries, electronic health records and administrative databases, are increasingly used in healthcare intervention research. A Consolidated Standards of Reporting Trials (CONSORT) statement extension for trials conducted using cohorts and routi...

This survey analysis of randomized clinical trials registered within 100 days of the first reported case of coronavirus disease 2019 assessed recruitment and results reporting.

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...