Julian Hirt

Background: We aimed to systematically identify and assess known potential confounders for the design of a target trial emulation on multiple sclerosis and to investigate its feasibility. Methods: We used the comparison of two drugs for relapsing-remitting multiple sclerosis. We conducted a systematic literature analysis (date of last search November 2, 2023) of observational studies and randomized trials, qualitative interviews, and a quantitative survey with clinicians. All identified potential confounders were categorized and classified by clinical importance. We estimated the resource use per study step and per identified potential confounder. Results: We assessed 53 observational studies and 27 randomized trials, surveyed 8 clinicians, and conducted 8 interviews with clinical experts. We identified a total of 160 individual potential confounders. While most of these were identified in the literature ( n = 125, 78%), interviews revealed an additional 35 (22%) factors. Of the 17 confounders rated by clinicians as very important for treatment decisions, 9 were identified by interviews (53%). All the potential confounders related to patient perspective were identified in interviews only. Across all data sources, the 5 most frequently considered factors were age ( n = 71), gender/sex ( n = 62), disability status ( n = 62), disease duration ( n = 53), and relapses ( n = 44); these were all considered in 16 (30%) of the observational studies. Sixty-two person-days were deemed necessary to identify the 160 potential confounders. Conclusions: There was a substantial discrepancy between factors considered when making treatment decisions and the confounders considered in studies. Even with extensive efforts, it is likely that for observational studies assessing treatment effects their key assumption of no unmeasured confounding is currently not met, and they will have challenges to provide credible real-world evidence due to serious concerns of confounding bias.

Background: Methods research aims to develop, evaluate, refine, or provide guidance on research methods, support their implementation or de-implementation, or synthesize existing methods research. Many types of methods research appear in health research journals, but their labels, definitions, and boundaries remain unclear. This complicates planning, reporting, indexing, and teaching, and limits the visibility of the field. We aimed to develop, refine and pilot-test a typology for recognising, describing, and classifying methods research.Methods: An international panel of 11 methodologists developed the typology through written feedback, structured group discussions, and iterative revision. In two testing rounds, panel members independently applied the typology to 52 methods research articles from 26 journals, generating 494 article assessments. We used the results to refine definitions and labels, add boundary notes, and document remaining disagreements.Results: TYPE-ME defines methods research and organizes it along two cross-cutting dimensions: approach (“how?”, 15 types) and objective (“why?”, 14 types). Testing clarified difficult boundaries and led to a condensed version that distinguishes 10 types for quick orientation: theory-based methods research; simulation studies; methods research based on real data; methodological randomized studies; surveys, interviews, or focus groups; consensus studies; studies of applied methods; syntheses of methods research; guidance for applying, reporting, or assessing methods; and methodological implementation research. Detailed type descriptions, boundary notes, and examples appear in an accompanying document and at www.methods-research.org.Conclusions: TYPE-ME offers a common reference for recognising, describing, and classifying methods research, and can support its planning, reporting, indexing, and teaching. As a living typology, it will evolve through application, user feedback, and further testing.

Background: Assessing the uptake of clinical trial results in evidence syntheses can inform how individual trials impact clinical knowledge. We systematically assessed the extent to which clinical trial results publications from trials conducted at German university medical centers were cited in Cochrane Reviews and included in their body of evidence.Methods: Using forward citation searching in OpenAlex and PubMed, we identified Cochrane Reviews citing clinical trial result publications (CTRPs) from trials conducted at German university medical centers and completed between 2009 and 2017. Citations were classified as included, excluded, or other based on Cochrane’s structured reference categories. Cochrane Reviews with unstructured citations were manually assessed. For the main analysis, we focused on citations classified as included in the body of evidence, as these were considered to inform review results. We additionally conducted an in-depth manual exploration of citation context in a purposively selected subsample.Results: Of 1,920 CTRPs, 385 (20.1 %) were cited by at least one Cochrane Review, and 222 (11.6%) were included in the body of evidence. CTRPs included in the body of evidence were more often randomized, blinded, and multinational compared to CTRPs not included in the body of evidence or not cited in Cochrane Reviews. There was substantial heterogeneity in how included CTRPs contributed to the results of a Cochrane Review, ranging from no contribution to quantitative synthesis to major influence across multiple meta-analyses.Discussion: Only a limited proportion of German clinical trials are incorporated into Cochrane Reviews, showing restricted translation into evidence-based knowledge systems. These citation-based frequency analyses may even overestimate the actual impact of clinical trials on the results of evidence synthesis.

Background: Relatives of nursing home residents are deeply involved in care relationships that extend far beyond visiting routines. However, their broader personhood is often overlooked, with existing research focusing on functional roles. This meta‐synthesis aims to explore how relatives experience “being relative” within institutional long‐term care, highlighting the complexity of their identity beyond institutional expectations. Methods: We conducted a qualitative meta‐synthesis of 59 per‐reviewed studies using Thomas and Harden's thematic synthesis approach. We systematically searched four databases (MEDLINE, CINAHL, Emcare, and PsycInfo) from inception to 17. In January 2024 and conducted citation tracking. Grounded in a social constructionist perspective, we conceptualised “being relative” as a relational identity co‐constructed through everyday interactions with staff in an institutional context. Results: Four interconnected themes characterise relatives: (i) Managing Ambiguity (navigating emotional complexity between gratitude and criticism), (ii) Fluid and Overlapping Roles (continuously shifting between advocacy, observation, and mediation), (iii) Dynamic Relationship Development (evolving connections with staff through recognition and challenge cycles), and (iv) Negotiating Care Responsibility (ongoing adaptation of involvement patterns). These themes form a cyclical model illustrating how relatives continuously navigate between institutional expectations and authentic experiences. Rather than inhabiting static roles, relatives engage in dynamic positioning processes, constantly adapting and reinterpreting their place within care settings. Conclusions: “Being relative” represents a dynamic process of continuous adaptation and meaning‐making within institutional constraints, extending beyond functional role assignments. Our cyclical model challenges reductionist approaches and emphasises the need for person‐centred care that recognises relatives as whole persons with complex identities and emotional needs. By acknowledging the person behind the institutional “mask,” care facilities can improve relatives' experiences, enhance care quality for residents, and increase staff satisfaction—demonstrating the potential of truly person‐centred approaches in long‐term care.

Background: Family carers of people with dementia face particularly stressful and time‐intensive care situations, yet their involvement in research is vital to understanding and addressing their specific needs. To inform involvement approaches, it is important to understand activities, roles, barriers and enablers associated with involving this group. This scoping review aimed to identify, map and summarise evidence on the involvement of family carers in dementia care research. Methods: We conducted a scoping review following JBI methodological guidance. Empirical studies involving family carers of people with dementia who actively contributed to research processes were included irrespective of study design. We systematically searched MEDLINE, CINAHL, Scopus and PsycInfo, complemented by backward citation searching, searches of relevant evidence syntheses and an expert survey. Two researchers independently screened a randomly selected 20% of titles/abstracts and full texts. Data items were organised into six categories and guided the charting process. Findings were synthesised descriptively and narratively. Consultation with four family carers was carried out to contextualise and enrich the results. Results: Forty‐eight studies published between 2002 and 2026 met inclusion criteria, most using qualitative designs. Research contexts included development of social or digital interventions, Patient and Public Involvement, implementation, exploration, evaluation and adaptation. Forty‐five studies reported involvement during the execution phase, six in the preparatory and nine in the translational phase. In 35 studies, family carers acted as co‐thinkers, in 10 as partners and in 1 as decision‐makers. Seven studies reported barriers and enablers, while 17 reported impacts of involvement on carers and on the respective projects. Conclusion: Dementia care research involving family carers as co‐researchers shows heterogeneous and often limited methodological reporting. Meaningful involvement may benefit from careful considerations of roles, potential barriers and enablers and expected impacts. More research is needed on strategies that enable meaningful involvement and on formalised methods for recording and reporting impact. Patient or Public Contribution: The impetus for this scoping review came from a group of family carers of people with dementia who had worked with us in a previous project and shared with us their lived experiences and difficulties. In collaboration with them, we raised the questions that are described in the scoping review. During the scoping review, family carers were also asked to give their views on the findings and share their thoughts.

Systematic Review (SR) is a prosperous study type in modern medicine and beyond. Many SR authors complement their primary database searches by supplementary techniques. Among these, citation-based techniques known as citation searching (CS) are widespread. Unranked Direct CS (UDCS) to identify directly cited and citing literature of seed references is currently most prevalent. Ranked (In)direct CS (RICS) additionally collects co-cited and co-citing literature combined with a ranking and cut-off procedure. However, RICS workflows remain non-standardized and tedious, and associated benefits unclear. This work aims to create a framework for the prospective international comparison of supplementary UDCS and RICS. To prime RICS research, we developed the open-source Co*Citation Network application and assessed parallel supplementary UDCS and RICS retrospectively in three completed SRs and prospectively in one case study. Automated RICS collected and ranked cited, citing, co-cited, and co-citing literature of seed references from OpenAlex database and applied an empirical rank cut-off to approximate the volume of UDCS results. In RICS compared to UDCS, we consistently noted higher overlap with primary database search results. Title/abstract screening in the case study showed a precision (number needed to read) of 1.8% (57) for UDCS and 2.1% (48) for RICS results. After full text screening, two additional articles were included for review, one of which was identified by UDCS and RICS, and one exclusively by UDCS. The present study indicates potential benefits of RICS for SR authors and will enable the formation of a research consortium to compare supplementary UDCS and RICS on larger scale. Highlights: What is already known?: Citation searching is a widespread supplementary search technique in systematic reviews to complement the results of the primary literature search in bibliographic databases. Compared to traditional citation searching (UDCS), Ranked (In)direct Citation Searching (RICS) which additionally incorporates co-cited and co-citing literature with a relevance ranking and cut-off procedure has been proposed as a potentially more effective approach, but has only been evaluated in proof-of-concept studies. What is new?: The open-source Co*Citation Network application is introduced: the first tool to automate parallel UDCS and RICS on the basis of the OpenAlex citation index. For the first time, parallel supplementary UDCS and RICS were applied and compared within a prospective systematic review, providing a concrete, replicable workflow. The results indicate that RICS results may be more relevant than UDCS results. Potential impact for RSM readers: The proposed supplementary UDCS and RICS workflow and ready-to-use collaboration infrastructure allow systematic review teams worldwide to contribute data to a large-scale comparative study.

Healthcare professionals, such as medical doctors, nurses, and physiotherapists commit to lifelong learning and to provide evidence-based healthcare. Despite this, surveys have found that medical doctors’ ability to find, analyse, and interpret scientific evidence is poor, which severely impairs the ability to stay updated. Thus, healthcare professionals should have basic competences to find relevant, updated biomedical evidence in the shape of systematic reviews and randomised clinical trials. Simple, pragmatic searches can be valuable to identify such evidence. In this paper, we provide a simple 4-step guidance on how to find systematic reviews and randomised clinical trials from commonly used databases and search engines like PubMed, the Cochrane Library, and Google Scholar. We highlight the World Health Organization International Clinical Trial Registry Platform to find planned and ongoing clinical trials and PROSPERO to find planned and ongoing systematic reviews. We give some background knowledge on each resource and tips to successful searches. Our guidance is intended as an evidence-based, pragmatic overview for healthcare professionals and researchers who would like to quickly answer specific questions to make a clinical decision, such as choosing between different treatments, or in the context of research purposes to find evidence on a certain topic. It is not intended as guidance for exhaustive searches needed for conducting systematic reviews.

Introduction: Health researchers benefit from methods guidance (MG) for planning, conducting, analyzing and interpreting research studies. How to develop MG that is trustworthy and researcher-friendly is unclear; existing strategies for developing MG are fragmented and lack a coherent framework. The STrategies for developing REseArch Methods guidance (STREAM) project aims to provide such a framework for developers of MG. As a first step, we reviewed the literature to identify proposed and applied strategies for developing MG and explored possible knowledge gaps.Methods: We conducted two literature reviews. First, a scoping review of the methodological literature to identify proposed strategies for developing MG. Second, a review of a purposeful sample of recently published MG articles to examine strategies applied in practice. We applied a qualitative content analysis to both sets of publications using one shared codebook. In addition, to identify possible knowledge gaps, we contrasted the findings with the established development processes for clinical practice guidelines and reporting guidelines.Results: The first review included 17 publications and the second review 102 MG articles. We identified possible development steps including assessing the need for MG, establishing a working group, considering the findings from methodological studies, gathering input from interest-holders, testing the new MG, and disseminating and implementing MG. In addition, we identified various approaches to perform the steps including systematic reviews of previous guidance, reviews of methodological practice, simulation studies, surveys or interviews of interest-holders, consensus methods, and public review. Mapping these findings with established development processes identified areas that have so far received limited attention within MG development, including the concept of methodological evidence, judging the quality of methodological evidence, reporting of MG, and approaches to implementation.Conclusion: This study provides an overview of proposed and applied strategies for developing MG, highlights needs for conceptual development, and provides a structured starting point for guidance for developing MG.

Background and Aims: Immunotherapies for cancers are tested in large numbers of clinical trials. It is difficult 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 designed the Cancer Immunotherapy Evidence Living (CIEL) Library. Methods: We included planned, ongoing, and completed interventional trials of immunotherapies for cancer, regardless of trial design (e.g., randomization, blinding, and type of comparator). We systematically searched PubMed (for published reports) and ClinicalTrials.gov (for registered clinical trials). PubMed‐retrieved records were screened using the AI‐assisted software ASReview and manually extracted and curated. We imported data from ClinicalTrials.gov using the Clinical Trials Transformation Initiative database, which then requires further curation. The CIEL‐Library was implemented as a web application. It also contained the “Match My Patient” feature, a patient‐centered clinical decision support system, aiming to filter planned, ongoing, or completed trials based on four patient characteristics (disease staging, previous treatments, performance status, and location). We piloted our database with one type of cancer immunotherapy, the tumor‐infiltrating lymphocytes (TIL) transfer. The CIEL‐Library was a prototype and no further developments are planned. Conclusions: The CIEL‐Library offers a blueprint for a dynamic evidence synthesis infrastructure by providing a collection of clinical trials with curated trial characteristics and results. This blueprint may be applied across fields, specialties, and topics. The main challenges to making a database of clinical trials are the time and resources needed to populate it with curated and updated data. The CIEL‐Library project highlights the potential and the main limitations of designing trial databases intended to be used in routine care.