Population characteristics as important contextual factors in rheumatological trials: an exploratory meta-epidemiological study from an OMERACT Working Group.

OBJECTIVES: To explore whether trial population characteristics modify treatment responses across various interventions, comparators and rheumatic conditions. METHODS: In this meta-epidemiological study, we included trials from systematic reviews available from the Cochrane Musculoskeletal Group published up to 23 April 2019 in Cochrane Library with meta-analyses of five or more randomised controlled trials (RCTs) published from year 2000. From trial reports, we extracted data on 20 population characteristics. For characteristics with sufficient data (ie, available for ≥2/3 of the trials), we performed multilevel meta-epidemiological analyses. RESULTS: We identified 19 eligible systematic reviews contributing 187 RCTs (212 comparisons). Only age and sex were explicitly reported in ≥2/3 of the trials. Using information about the country of the trials led to sufficient data for five further characteristics, that is, 7 out of 20 (35%) protocolised characteristics were analysed. The meta-regressions showed effect modification by economic status, place of residence, and, nearly, from healthcare system (explaining 4.8%, 0.9% and 1.5% of the between-trial variation, respectively). No effect modification was demonstrated from age, sex, patient education/health literacy or predominant religion. CONCLUSIONS: This study demonstrates the scarce reporting of most population characteristics, hampering investigation of their impact with meta-research. Our sparse results suggest that place of residence (ie, continent of the trial), economic status (based on World Bank classifications) and healthcare system (based on WHO index for health system performance) may be important in explaining the variation in treatment response across trials. There is an urgent need for consistent reporting of important population characteristics in trials. PROSPERO REGISTRATION NUMBER: CRD42019127642.

Potential predatory and legitimate biomedical journals: can you tell the difference? A cross-sectional comparison.

BACKGROUND: The Internet has transformed scholarly publishing, most notably, by the introduction of open access publishing. Recently, there has been a rise of online journals characterized as 'predatory', which actively solicit manuscripts and charge publications fees without providing robust peer review and editorial services. We carried out a cross-sectional comparison of characteristics of potential predatory, legitimate open access, and legitimate subscription-based biomedical journals. METHODS: On July 10, 2014, scholarly journals from each of the following groups were identified - potential predatory journals (source: Beall's List), presumed legitimate, fully open access journals (source: PubMed Central), and presumed legitimate subscription-based (including hybrid) journals (source: Abridged Index Medicus). MEDLINE journal inclusion criteria were used to screen and identify biomedical journals from within the potential predatory journals group. One hundred journals from each group were randomly selected. Journal characteristics (e.g., website integrity, look and feel, editors and staff, editorial/peer review process, instructions to authors, publication model, copyright and licensing, journal location, and contact) were collected by one assessor and verified by a second. Summary statistics were calculated. RESULTS: Ninety-three predatory journals, 99 open access, and 100 subscription-based journals were analyzed; exclusions were due to website unavailability. Many more predatory journals' homepages contained spelling errors (61/93, 66%) and distorted or potentially unauthorized images (59/93, 63%) compared to open access journals (6/99, 6% and 5/99, 5%, respectively) and subscription-based journals (3/100, 3% and 1/100, 1%, respectively). Thirty-one (33%) predatory journals promoted a bogus impact metric - the Index Copernicus Value - versus three (3%) open access journals and no subscription-based journals. Nearly three quarters (n = 66, 73%) of predatory journals had editors or editorial board members whose affiliation with the journal was unverified versus two (2%) open access journals and one (1%) subscription-based journal in which this was the case. Predatory journals charge a considerably smaller publication fee (median $100 USD, IQR $63-$150) than open access journals ($1865 USD, IQR $800-$2205) and subscription-based hybrid journals ($3000 USD, IQR $2500-$3000). CONCLUSIONS: We identified 13 evidence-based characteristics by which predatory journals may potentially be distinguished from presumed legitimate journals. These may be useful for authors who are assessing journals for possible submission or for others, such as universities evaluating candidates' publications as part of the hiring process.

Rapid review method series: interim guidance for the reporting of rapid reviews.

Rapid reviews (RRs) are produced using abbreviated methods compared with standard systematic reviews (SR) to expedite the process for decision-making. This paper provides interim guidance to support the complete reporting of RRs. Recommendations emerged from a survey informed by empirical studies of RR reporting, in addition to collective experience. RR producers should use existing, robustly developed reporting guidelines as the foundation for writing RRs: notably Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 (PRISMA 2020; reporting for SRs), but also preferred reporting items for overviews of reviews (PRIOR) items (reporting for overviews of SRs) where SRs are included in the RR. In addition, a minimum set of six items were identified for RRs: three items pertaining to methods and three addressing publication ethics. Authors should be reporting what a priori-defined iterative methods were used during conduct, what distinguishes their RR from an SR, and knowledge user (eg, policymaker) involvement in the process. Explicitly reporting deviations from standard SR methods, including omitted steps, is important. The inclusion of publication ethics items reflects the predominance of non-journal published RRs: reporting an authorship byline and corresponding author, acknowledging other contributors, and reporting the use of expert peer review. As various formats may be used when packaging and presenting information to decision-makers, it is practical to think of complete reporting as across a set of explicitly linked documents made available in an open-access journal or repository that is barrier-free. We encourage feedback from the RR community of the use of these items as we look to develop a consolidated list in the development of PRISMA-RR.

Effectiveness of e-cigarettes as a stop smoking intervention in adults: a systematic review.

BACKGROUND: This systematic review aims to identify the benefits and harms of electronic cigarettes (e-cigarettes) as a smoking cessation aid in adults (aged ≥ 18 years) and to inform the development of the Canadian Task Force on Preventive Health Care's (CTFPHC) clinical practice guidelines on e-cigarettes. METHODS: We searched Ovid MEDLINE®, Ovid MEDLINE® Epub Ahead of Print, In-Process & Other Non-Indexed Citations, PsycINFO, Embase Classic + Embase, and the Cochrane Library on Wiley. Searches were conducted from January 2016 to July 2019 and updated on 24 September 2020 and 25 January 2024. Two reviewers independently performed title-abstract and full-text screening according to the pre-determined inclusion criteria. Data extraction, quality assessments, and the application of Grading of Recommendations Assessment, Development and Evaluation (GRADE) were performed by one independent reviewer and verified by another. RESULTS: We identified 18 studies on 17 randomized controlled trials that compared e-cigarettes with nicotine to e-cigarettes without nicotine and e-cigarettes (with or without nicotine) to other interventions (i.e., no intervention, waitlist, standard/usual care, quit advice, or behavioral support). Considering the benefits of e-cigarettes in terms of smoking abstinence and smoking frequency reduction, 14 studies showed small or moderate benefits of e-cigarettes with or without nicotine compared to other interventions; although, with low, very low or moderate evidence certainty. With a focus on e-cigarettes with nicotine specifically, 12 studies showed benefits in terms of smoking abstinence when compared with usual care or non-nicotine e-cigarettes. In terms of harms following nicotine or non-nicotine e-cigarette use, 15 studies reported mild adverse events with little to no difference between groups and low to very low evidence certainty. CONCLUSION: The evidence synthesis on the e-cigarette's effectiveness shows data surrounding benefits having low to moderate evidence certainty for some comparisons and very low certainty for others, indicating that e-cigarettes may or probably increase smoking cessation, whereas, for harms, there is low to very low evidence certainty. Since the duration for outcome measurement varied among different studies, it may not be long-term enough for Adverse Events (AEs) to emerge, and there is a need for more research to understand the long-term benefits and potential harms of e-cigarettes. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42018099692.

Embracing unity at OMERACT: Valuing equity, promoting diversity, fostering inclusivity.

OBJECTIVE: To increase awareness and understanding of the principles of Equity, Diversity, and Inclusivity (EDI) within Outcome Measures in Rheumatology's (OMERACT) members. For this, we aimed to obtain ideas on how to promote and foster these principles within the organization and determine the diversity of the current membership in order to focus future efforts. METHODS: We held a plenary workshop session at OMERACT 2023 with roundtable discussions on barriers and solutions to increased diversity within OMERACT. We conducted an anonymous, web-based survey of members to record characteristics including population group, gender identity, education level, age, and ability. RESULTS: The workshop generated ideas to increase diversity of participants across the themes of building relationships [12 topics], materials and methods [5 topics], and conference-specific [6 topics]. Four hundred and seven people responded to the survey (25 % response rate). The majority of respondents were White (75 %), female (61 %), university-educated (94 %), Christian (42 %), spoke English at home (60 %), aged 35 to 55 years (50 %), and did not report a disability (64 %). CONCLUSION: OMERACT is committed to improving its diversity. Next steps include strategic recruitment of members to the EDI working group, drafting an EDI mission statement centering equity and inclusivity in the organization, and developing guidance for the OMERACT Handbook to help all working groups create actionable plans for promoting EDI principles.

Strategies to promote implementation of core outcomes for medication adherence trials in rheumatology: A report from the OMERACT-Adherence Group.

OBJECTIVES: To identify barriers, facilitators, and strategies for future implementation of the OMERACT-Adherence Core Outcome Set (COS) in medication adherence trials for rheumatic conditions. METHODS: Preliminary Delphi survey findings were discussed at OMERACT 2023, utilising the Consolidated Framework for Implementation Research 2 to identify implementation barriers, facilitators, and solutions. RESULTS: Implementation strategies included simplifying the COS definitions, making it adaptabile for clinical practice and drug trials, adherence trial training workshops, and collaborating with key stakeholders such as payers and other COS developers. CONCLUSION: Ongoing collaboration with individuals and organisations within and beyond rheumatology ensures broader applicability of OMERACT-Adherence COS.

Screening for depression in children and adolescents in primary care or non-mental health settings: a systematic review update.

BACKGROUND: The transition from childhood to adolescence is associated with an increase in rates of some psychiatric disorders, including major depressive disorder, a debilitating mood disorder. The aim of this systematic review is to update the evidence on the benefits and harms of screening for depression in primary care and non-mental health clinic settings among children and adolescents. METHODS: This review is an update of a previous systematic review, for which the last search was conducted in 2017. We searched Ovid MEDLINE® ALL, Embase Classic+Embase, PsycINFO, Cochrane Central Register of Controlled Trials, and CINAHL on November 4, 2019, and updated on February 19, 2021. If no randomized controlled trials were found, we planned to conduct an additional search for non-randomized trials with a comparator group. For non-randomized trials, we applied a non-randomized controlled trial filter and searched the same databases except for Cochrane Central Register of Controlled Trials from January 2015 to February 2021. We also conducted a targeted search of the gray literature for unpublished documents. Title and abstract, and full-text screening were completed independently by pairs of reviewers. RESULTS: In this review update, we were unable to find any randomized controlled studies that satisfied our eligibility criteria and evaluated the potential benefits and harms of screening for depression in children and adolescents. Additionally, a search for non-randomized trials yielded no studies that met the inclusion criteria. CONCLUSIONS: The findings of this review indicate a lack of available evidence regarding the potential benefits and harms of screening for depression in children and adolescents. This absence of evidence emphasizes the necessity for well-conducted clinical trials to evaluate the effectiveness of depression screening among children and adolescents in primary care and non-mental health clinic settings. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42020150373 .

Effectiveness of smoking cessation interventions among adults: an overview of systematic reviews.

BACKGROUND: This overview of reviews aims to identify evidence on the benefits (i.e. tobacco use abstinence and reduction in smoking frequency) and harms (i.e. possible adverse events/outcomes) of smoking cessation interventions among adults aged 18 years and older. METHODS: We searched Medline, Embase, PsycINFO, Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effects, the CADTH Health Technology Assessment Database and several other websites for grey literature. Searches were conducted on November 12, 2018, updated on September 24, 2020, with publication years 2008 to 2020. Two reviewers independently performed title-abstract and full-text screening considering pre-determined inclusion criteria. Data extraction and quality assessments were initially completed by two reviewers independently (i.e. 73% of included studies (n = 22)) using A Measurement Tool to Assess Systematic Reviews-2 (AMSTAR 2), and the remainder done by one reviewer and verified by another due to resources and feasibility. The application of Grading of Recommendations Assessment, Development and Evaluation (GRADE) was performed by one independent reviewer and verified by another. RESULTS: A total of 22 Cochrane systematic reviews evaluating the impact of smoking cessation interventions on outcomes such as tobacco use abstinence, reduction in smoking frequency, quality of life and possible adverse events were included. Pharmaceutical (i.e. varenicline, cytisine, nicotine replacement therapy (NRT), bupropion) and behavioural interventions (i.e. physician advice, non-tailored print-based self-help materials, stage-based individual counselling, etc.) showed to have increased smoking cessation; whereas, data for mobile phone-based interventions including text messaging, hypnotherapy, acupuncture, continuous auricular stimulation, laser therapy, electrostimulation, acupressure, St John's wort, S-adenosyl-L-methionine (SAMe), interactive voice response systems and other combination treatments were unclear. Considering harms related to smoking cessation interventions, small/mild harms (i.e. increased palpitations, chest pain, nausea, insomnia, headache) were observed following NRT, varenicline and cytisine use. There were no data on harms related to behavioural therapies (i.e. individual or group counselling self-help materials, internet interventions), combination therapies or other therapies (i.e. laser therapy, electrostimulation, acupressure, St John's wort, SAMe). CONCLUSION: Results suggest that pharmacological and behavioural interventions may help the general smoking population quit smoking with observed small/mild harms following NRT or varenicline. Consequently, evidence regarding ideal intervention strategies and the long-term impact of these interventions for preventing smoking was unclear. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42018099691.

Advancing composite outcome measures: Insights on weighting components from OMERACT 2023.

OBJECTIVE: The OMERACT Composite Working Group hosted a workshop at OMERACT 2023 to explore the complexities of weighting components in the development of composite outcomes. This study presents the methodology and findings of this workshop, exploring the complexities of weighting the individual components of composite outcome measures. METHODS: The workshop featured a multifaceted program, beginning with a plenary session that introduced the concept of composite outcomes, shared a patient's journey with rheumatic disease through a narrative, illustrated a composite outcome for Osteoarthritis Flares, and outlined the five domains selected for this composite outcome. A breakout exercise engaged participants in ranking and assigning weights to these domains, followed by group discussions to reach a consensus on weights. The workshop concluded with another plenary session that discussed various weighting approaches, including discrete choice and conjoint analysis from the ANCA-Associated Vasculitis working group, and outlined future directions for research on composite outcome methods. RESULTS: The breakout exercise revealed the challenges in assigning relative importance to different domains, highlighting the variability in participant perspectives. Consensus discussions highlighted the diversity in approaches to weighting, the need for appropriate methods to determine domain weights and the impact of such weights on the interpretation of composite scores. CONCLUSION: The OMERACT 2023 workshop underscored the significance of a systematic approach to weighting components in composite outcome development. It highlighted the complexity of achieving consensus on the importance of domains and the role of incorporating the perspectives of patient research partners in this process. Future research directions include refining weighting methodologies, moving composites through the OMERACT Filter and enhancing understanding of their implications for clinical trials. The findings contribute to the ongoing discourse on optimizing composite outcome measures in rheumatology and beyond, advocating for a balanced integration of scientific rigour and patient-centeredness in their development.

Defining domains: developing consensus-based definitions for foundational domains in OMERACT core outcome sets.

OBJECTIVE: To develop a set of detailed definitions for foundational domains commonly used in OMERACT (Outcome Measures in Rheumatology) core domain sets. METHODS: We identified candidate domain definitions from prior OMERACT publications and websites and publications of major organizations involved in outcomes research for six domains commonly used in OMERACT Core Domain Sets: pain intensity, pain interference, physical function, fatigue, patient global assessment, and health-related quality of life. We conducted a two-round survey of OMERACT working groups, patient research partners, and then the OMERACT Technical Advisory Group to establish their preferred domain definitions. Results were presented at the OMERACT 2023 Methodology Workshop, where participants discussed their relevant lived experience and identified potential sources of variability giving the needed detail in our domain definitions. RESULTS: One-hundred four people responded to both rounds of the survey, and a preferred definition was established for each of the domains except for patient global assessment for which no agreement was reached. Seventy-five participants at the OMERACT 2023 Methodology Workshop provided lived experience examples, which were used to contextualise domain definition reports for each of the five domains. CONCLUSION: Using a consensus-based approach, we have created a detailed definition for five of the foundational domains in OMERACT core domain sets; patient global assessment requires further research. These definitions, although not mandatory for working groups to use, may facilitate the initial domain-match assessment step of instrument selection, and reduce the time and resources required by future OMERACT groups when developing core outcome sets.

Identification of outcomes in clinical studies of interventions for venous thromboembolism in non-pregnant adults: A scoping review.

BACKGROUND: The development of a core outcome set (COS), defined as an agreed minimum set of outcome domains that should be measured and reported in all trials of a specific disease, aims to increase the relevance of study findings to stakeholder groups and improve standardization. OBJECTIVES: As the first step in developing a COS for venous thromboembolism (VTE) treatment studies, we aimed to generate an inclusive list of unique outcomes reported in previous VTE treatment studies and classify them into domains and core areas. METHODS: MEDLINE, Embase and CENTRAL were searched for prospective studies reporting on interventions for VTE in non-pregnant adults. Study selection and data extraction were performed in blocks based on publication date, starting with 2015-2020 and subsequent 1-year periods, until no new outcome was identified. Outcomes were classified into domains, which are groups of closely related outcomes, and domains into four core areas including death, pathophysiological manifestations/abnormalities, life impact, and resource use. RESULTS: Of 7100 records identified, 240 publications were included, representing 165 distinct studies. A total of 205 unique outcomes were identified that were grouped into 48 domains; 30 (13%) studies covered at least three core areas; death was included in 102 (43%), pathophysiological manifestations/abnormalities in 218 (91%), life impact in 41 (17%), and resource use in 25 (10%) studies. CONCLUSION: Most VTE treatment studies evaluated pathophysiological features of VTE, but few studies reported outcomes that measured life impact or resource use. The findings will inform next steps in the development of a COS for VTE treatment studies.

A new taxonomy was developed for overlap across 'overviews of systematic reviews': A meta-research study of research waste.

Multiple 'overviews of reviews' conducted on the same topic ("overlapping overviews") represent a waste of research resources and can confuse clinicians making decisions amongst competing treatments. We aimed to assess the frequency and characteristics of overlapping overviews. MEDLINE, Epistemonikos and Cochrane Database of Systematic Reviews were searched for overviews that: synthesized reviews of health interventions and conducted systematic searches. Overlap was defined as: duplication of PICO eligibility criteria, and not reported as an update nor a replication. We categorized overview topics according to 22 WHO ICD-10 medical classifications, overviews as broad or narrow in scope, and overlap as identical, nearly identical, partial, or subsumed. Subsummation was defined as when broad overviews subsumed the populations, interventions and at least one outcome of another overview. Of 541 overviews included, 169 (31%) overlapped across similar PICO, fell within 13 WHO ICD-10 medical classifications, and 62 topics. 148/169 (88%) overlapping overviews were broad in scope. Fifteen overviews were classified as having nearly identical overlap (9%); 123 partial overlap (73%), and 31 subsumed (18%) others. One third of overviews overlapped in content and a majority covered broad topic areas. A multiplicity of overviews on the same topic adds to the ongoing waste of research resources, time, and effort across medical disciplines. Authors of overviews can use this study and the sample of overviews to identify gaps in the evidence for future analysis, and topics that are already studied, which do not need to be duplicated.

Screening for depression among the general adult population and in women during pregnancy or the first-year postpartum: two systematic reviews to inform a guideline of the Canadian Task Force on Preventive Health Care.

BACKGROUND: Depression affects an individual's physical health and mental well-being and, in pregnant and postpartum women, has specific adverse short- and long-term effects on maternal, child, and family health. The aim of these two systematic reviews is to identify evidence on the benefits and harms of screening for depression compared to no screening in the general adult and pregnant and postpartum populations in primary care or non-mental health clinic settings. These reviews will inform recommendations by the Canadian Task Force on Preventive Health Care. METHODS: We searched MEDLINE, Embase, PsycINFO, CINAHL, and the Cochrane Library using a randomized controlled trial filter, where applicable, October 4, 2018, and updated to May 11, 2020. We also searched for gray literature (e.g., websites of organizations of health professionals and patients). Study selection for depression screening trials was performed first on title and abstract, followed by full-text screening. Data extraction, assessment of the risk of bias using the Cochrane risk of bias tool, and application of Grading of Recommendations Assessment, Development and Evaluation were performed by one reviewer and validated by a second reviewer. RESULTS: A total of three trials were included. All three trials were included in the general adult review, while one of the three trials was included in the pregnant and postpartum review. We did not pool results due to substantial differences between studies and high risk of bias. In the general adult review, the first trial (n = 1001) evaluated whether screening for depression in adults with acute coronary syndrome compared to usual care improves health-related quality of life, depression symptoms, or harms of screening at 6, 12, and 18 months. There were little to no differences between the groups at 18 months for the outcomes. The second trial included adults (n = 1412) undergoing initial consultation for osteoarthritis, evaluated for depression and general health (mental and physical) after initial consultation and at 3, 6, and 12 months. The physical component score was statistically significantly lower (worse health) in the screened group at 6 months; however, this difference was not significant at 3 or at 12 months. There were no clinically important or statistically significant differences for other outcomes between groups at any time. The third trial (included in both reviews) reported on 462 postpartum women. At 6 months postpartum, fewer women in the screening group were identified as possibly depressed compared to the control group (RR 0.59, 95% confidence interval (CI) 0.39 to 0.89) and mean EPDS scores were also statistically significantly lower in the screened group (standardized mean difference 0.34 lower (95% CI 0.15 to 0.52 lower)). All other outcomes did not differ between groups at follow-up. There were serious concerns about the cut-offs used for the questionnaire used to screen, diagnostic confirmation, selective outcome reporting, and the reported magnitude of effects. DISCUSSION: There are limitations of the evidence included in the reviews. There was moderate certainty in the evidence from one trial that screening for depression in the general adult population in primary care or non-mental health clinic settings likely results in little to no difference on reported outcomes; however, the evidence was uncertain from the other two included trials. The evidence is very uncertain about the effect of screening for depression in pregnant or postpartum women in primary care or non-mental health clinic settings. Well-conducted and better-reported trials are needed that meet the screening trial criteria used in this review. SYSTEMATIC REVIEW REGISTRATION: Both protocols have been registered in the International Prospective Registry of Systematic Reviews (PROSPERO) [adult: CRD42018099690 ; pregnancy and postpartum: CRD42018099689 ] and published ( https://systematicreviewsjournal.biomedcentral.com/track/pdf/10.1186/s13643-018-0930-3 ).

Bibliometric study of 'overviews of systematic reviews' of health interventions: Evaluation of prevalence, citation and journal impact factor.

Overviews synthesising the results of multiple systematic reviews help inform evidence-based clinical practice. In this first of two companion papers, we evaluate the bibliometrics of overviews, including their prevalence and factors affecting citation rates and journal impact factor (JIF). We searched MEDLINE, Epistemonikos and Cochrane Database of Systematic Reviews (CDSR). We included overviews that: (a) synthesised reviews, (b) conducted a systematic search, (c) had a methods section and (d) examined a healthcare intervention. Multivariable regression was conducted to determine the association between citation density, JIF and six predictor variables. We found 1218 overviews published from 2000 to 2020; the majority (73%) were published in the most recent 5-year period. We extracted a selection of these overviews (n = 541; 44%) dated from 2000 to 2018. The 541 overviews were published in 307 journals; CDSR (8%), PLOS ONE (3%) and Sao Paulo Medical Journal (2%) were the most prevalent. The majority (70%) were published in journals with impact factors between 0.05 and 3.97. We found a mean citation count of 10 overviews per year, published in journals with a mean JIF of 4.4. In multivariable analysis, overviews with a high number of citations and JIFs had more authors, larger sample sizes, were open access and reported the funding source. An eightfold increase in the number of overviews was found between 2009 and 2020. We identified 332 overviews published in 2020, which is equivalent to one overview published per day. Overviews perform above average for the journals in which they publish.

Composite outcomes at OMERACT: Multi-outcome domains and composite outcome domains.

The OMERACT Technical Advisory Group recognises that working groups during the process of creating a core outcome set may identify an outcome domain that would be best represented as a composite that encapsulates these component outcome domains by bringing them together into a single outcome. A multi-outcome domain (MOD) is a within-patient combination of component outcomes, and an individual patient's evaluation depends on the observation of all of the components in that patient with a single overall rating determined according to a specified rule; which is often applicable when we consider a disease activity score. A composite outcome domain (COD) consists of a number of component outcomes and is defined as the occurrence in a patient of one, some or all of these specified components; which is often applicable when we consider the risk of adverse events or remission criteria. We review the general benefits, challenges, reporting and interpretation of using MODs and CODs. The development of the MOD or COD instrument for an OMERACT core outcome measurement set is considered through four distinct steps: choosing relevant outcome domains; finding high quality instruments for each of these outcome domains; weighting the outcome domain instruments in the MOD/COD instrument; and putting MOD/COD instrument through the OMERACT Filter. Guidance and training are in preparation for working groups who will be completing the OMERACT Instrument Selection Algorithm (OFISA). As for other initiatives in OMERACT, we will seek feedback from OMERACT working groups who complete the development of their MOD/COD, which will then be incorporated into the refinement of the guidance and training.

The evolution of instrument selection for inclusion in core outcome sets at OMERACT: Filter 2.2.

INTRODUCTION: OMERACT uses an evidence-based framework known as the 'OMERACT Filter Instrument Selection Algorithm' (OFISA) to guide decisions in the assessment of outcome measurement instruments for inclusion in a core outcome set for interventional and observational clinical trials. METHODS: A group of OMERACT imaging and patient-centered outcome methodologists worked with imaging outcome groups to facilitate the selection of imaging outcome measurement instruments using the OFISA approach. The lessons learned from this work influenced the evolution to Filter 2.2 and necessitated changes to OMERACT's documentation and processes. RESULTS: OMERACT has revised documentation and processes to incorporate the evolution of instrument selection to Filter 2.2. These revisions include creation of a template for detailed definitions of the target domain which is a necessary first step for instrument selection, modifications to the Summary of Measurement Properties (SOMP) table to account for sources of variability, and development of standardized reporting tables for each measurement property. CONCLUSIONS: OMERACT Filter 2.2 represents additional modifications of the OMERACT guide for working groups in their rigorous assessment of measurement properties of instruments of various types, including imaging outcome measurement instruments. Enhanced reporting aims to increase the transparency of the evidence base leading to judgements for the endorsement of instruments in core outcome sets.

Harms reported by patients in rheumatology drug trials: a systematic review of randomized trials in the cochrane library from an OMERACT working group.

BACKGROUND: Underreporting of harms in randomized controlled trials (RCTs) may lead to incomplete or erroneous assessments of the perceived benefit-to-harm profile of an intervention. To compare benefit with harm in clinical practice and future clinical studies, adverse event (AE) profiles including severity need to be understood. Even though patients report harm symptoms earlier and more frequently than clinicians, rheumatology RCTs currently do not provide a reporting framework from the patient's perspective regarding harms. Our objective for this meta-research project was to identify AEs in order to determine harm clusters and whether these could be self-reported by patients. Our other objective was to examine reported severity grading of the reported harms. METHODS: We considered primary publications of RCTs eligible if they were published between 2008 and 2018 evaluating pharmacological interventions in patients with a rheumatic or musculoskeletal condition and if they were included in Cochrane reviews. We extracted data on harms such as reported AE terms together with severity (if described), and categorized AE- and severity-terms into overall groups. We deemed all AEs with felt components appropriate for patient self-reporting. RESULTS: The literature search identified 187 possible Cochrane reviews, of which 94 were eligible for evaluation, comprising 1,297 articles on individual RCTs. Of these RCTs, 93 pharmacological trials met our inclusion criteria (including 31,023 patients; representing 20,844 accumulated patient years), which reported a total of 21,498 AEs, corresponding to 693 unique reported terms for AEs. We further sub-categorized these terms into 280 harm clusters (i.e., themes). AEs appropriate for patient self-reporting accounted for 58% of the AEs reported. Among the reported AEs, we identified medical terms for all of the 117 harm clusters appropriate for patient reporting and lay language terms for 86%. We intended to include severity grades of the reported AEs, but there was no evidence for systematic reporting of clinician- or patient-reported severity in the primary articles of the 93 trials. However, we identified 33 terms suggesting severity, but severity grading was discernible in only 9%, precluding a breakdown by severity in this systematic review. CONCLUSIONS: Our results support the need for a standardized framework for patients' reporting of harms in rheumatology trials. Reporting of AEs with severity should be included in future reporting of harms, both from the patients' and investigators' perspectives. REGISTRATION: PROSPERO: CRD42018108393.

Screening for depression in children and adolescents: a protocol for a systematic review update.

BACKGROUND: Major depressive disorder is common, debilitating, and affects feelings, thoughts, mood, and behaviors. Childhood and adolescence are critical periods for the development of depression and adolescence is marked by an increased incidence of mental health disorders. This protocol outlines the planned scope and methods for a systematic review update that will evaluate the benefits and harms of screening for depression in children and adolescents. METHODS: This review will update a previously published systematic review by Roseman and colleagues. Eligible studies are randomized controlled trials (RCTs) assessing formal screening in primary care to identify children or adolescents not already self-reporting symptoms of, diagnosed with, or treated for depression. If no or only a single RCT is available, we will consider controlled studies without random assignment. Studies of participants with characteristics associated with an elevated risk of depression will be analyzed separately. Outcomes of interest are symptoms of depression, classification of major depressive disorder based on a validated diagnostic interview, suicidality, health-related quality of life, social function, impact on lifestyle behavior (e.g., substance use, school performance, lost time at work, or school), false-positive results, overdiagnosis, overtreatment, labeling, and other harms such as those arising from treatment. We will search MEDLINE, Embase, PsycINFO, CINAHL, the Cochrane Library, and grey literature sources. Two reviewers will independently screen the titles and abstracts using the liberal accelerated method. Full-text screening will be performed independently by two reviewers using pre-specified eligibility criteria. Data extraction and risk of bias assessments will be performed independently by two reviewers. Pre-planned analyses, including subgroup and sensitivity analyses, are detailed within this protocol. Two independent reviewers will assess and finalize through consensus the certainty of evidence using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach, and prepare GRADE evidence profiles and summary of findings tables for each outcome of interest. DISCUSSION: The systematic review will provide a current state of the evidence of benefits and harms of depression screening in children and adolescents. These findings will be used by the Canadian Task Force on Preventive Health Care to inform the development of recommendations on depression screening. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42020150373.

Combination Tests in the Diagnosis of Chronic Periprosthetic Joint Infection: Systematic Review and Development of a Stepwise Clinical Decision-Making Tool.

BACKGROUND: Our objective was to identify combination tests used to diagnose chronic periprosthetic joint infection (PJI) and develop a stepwise decision-making tool to facilitate diagnosis. METHODS: We conducted a systematic review of existing combinations of serum, synovial, and tissue-based tests for diagnosing chronic PJI after hip or knee replacement. This work is an extension of our systematic review of single tests, from which we chose eligible studies that also described the diagnostic performance of combination tests. RESULTS: Thirty-seven eligible articles described the performance of 56 combination tests, of which 8 combinations had at least 2 studies informing both sensitivity and specificity. We also identified 5 types of combination tests: (1) a type-I Boolean combination, which uses Boolean logic (AND, OR) and usually increases specificity at the cost of sensitivity; (2) a type-II Boolean combination, which usually increases sensitivity at the cost of specificity; (3) a triage-conditional rule, in which the value of 1 test serves to triage the use of another test; (4) an arithmetic operation on the values of 2 tests; and (5) a model-based prediction rule based on a fitted model applied to biomarker values. CONCLUSIONS: Clinicians can initiate their diagnostic process with a type-II Boolean combination of serum C-reactive protein (CRP) and interleukin-6 (IL-6). False negatives of the combination can be minimized when the threshold is chosen to reach 90% to 95% sensitivity for each test. Once a joint infection is suspected on the basis of serum testing, joint aspiration should be performed. If joint aspiration yields a wet tap, a leukocyte esterase (LER) strip is highly recommended for point-of-care testing, with a reading of ++ or greater indicating PJI; a reading below ++ should be followed by one of the laboratory-based synovial tests. If joint aspiration yields a dry tap, clinicians should rely on preoperative tissue culture and histological analysis for diagnosis. Combinations based on triage-conditional, arithmetic, and model-based prediction rules require further research. LEVEL OF EVIDENCE: Diagnostic Level III. See Instructions for Authors for a complete description of levels of evidence.

Protocol for a scoping review of outcomes in clinical studies of interventions for venous thromboembolism in adults.

INTRODUCTION: Venous thromboembolism (VTE) is a common, potentially fatal yet treatable disease. Several advances in treatment of VTE have been made over the past decades, but definition and reporting of outcomes across those studies are inconsistent. Development of an international core outcome set for clinical studies of interventions for VTE addresses this lack of standardisation. The first step in the development of a core outcome set is to conduct a scoping review which aims to generate an inclusive list of unique outcomes that have been reported in previous studies. METHODS AND ANALYSIS: MEDLINE, Embase and the Cochrane Central Register of Controlled Trials will be searched with no language restriction for prospective studies reporting on interventions for treatment of VTE in patients who are adult and non-pregnant. Records will be sorted in reverse chronological order. Study screening and data extraction will be independently performed by two authors in blocks based on date of publication, starting with 2015 to 2020 and subsequent 1-year periods, until no new outcome measures are identified from the set of included studies. After homogenising spelling and combining outcomes with the same meaning, a list of unique outcomes will be determined. Those outcomes will be grouped into outcome domains. Qualitative analysis and descriptive statistics will be used to report results. ETHICS AND DISSEMINATION: Ethical approval is not required for this study. The results of this scoping review will be presented at scientific conferences, published in a peer-reviewed journal, and they will provide candidate outcome domains to be considered in subsequent steps in the development of a core outcome set for clinical studies of interventions for VTE. PROTOCOL REGISTRATION DETAILS: http://hdl.handle.net/10393/40459.