Applicability of trials in rheumatoid arthritis and osteoarthritis: A systematic review and meta-analysis of trial populations showing adequate proportion of women, but underrepresentation of elderly people

Objectives: To evaluate whether elderly people and women are adequately represented in randomized controlled trials (RCT) in rheumatoid arthritis (RA) and osteoarthritis (OA). Methods: Four systematic searches in MEDLINE yielded RCT in RA and OA on any intervention published in 2016 and 2017 and population-based studies (PBS) in RA and OA published between 2013 and 2017. Random effects meta-analyses estimated the pooled proportion of elderly people (defined as being ≥ 65 years old), the mean age, its standard deviation (SD), and the proportion of women stratified by disease (RA and OA) and study type (RCT and PBS). Stratified estimates were subsequently compared. Results: 265 RCT comprising 51,240 participants and 53 PBS comprising 523,630 participants were included. In both RA and OA, RCT included lower proportions of elderly people than PBS: RA –0.18 (95% confidence interval –0.22 to –0.13); OA –0.20 (–0.30 to –0.09); had lower mean ages: RA –5.2 years (–6.8 to –3.5); OA –4.7 years (–7.5 to –2.0); and smaller SD: RA –1.9 years (–2.6 to –1.3); OA –2.7 years (–4.2 to –1.2); (all comparisons: p ≤ 0.001). Proportions of women were comparable in RCT compared to PBS in both RA and OA. Conclusions: While women are adequately represented in RA and OA trials, the elderly are underrepresented, probably limiting applicability of current evidence to this growing subgroup. It is urgent to improve the inclusion of elderly people in clinical trials and study age as a determinant for outcome

Recruitment and Retention of Older People in Clinical Research: A Systematic Literature Review

OBJECTIVE: To identify barriers and solutions for the recruitment and retention of older (aged ≥65 years) people in clinical trials. DESIGN: Systematic literature review. METHODS: Three databases (Medline, Embase, and CENTRAL) were searched for articles reporting on barriers or solutions regarding the recruitment or retention of older people. Only original research articles were included. RESULTS: Fifty eligible articles were identified. Exclusion criteria were the most common cause of poor recruitment of older adults (mainly age and comorbidities). Patients' families or physicians often advised against participation (22% of included studies). Lack of interest (18%) and problems with transportation (18%) were also commonly cited as challenges. Fourteen trials (28%) reported that monitoring and adapting their recruitment methods helped, along with a flexible research team (26%) and provision of transportation (24%). Retention was impaired by death (12%), illness (8%), and loss of interest (6%). Methods with a positive effect on retention included financial incentives and regular information about the progress of the study (12%), a low staff turnover (12%), flexibility in appointment making (10%), and expression of appreciation by the staff through letters, gifts, and cards to the participants (10%). CONCLUSION: We identified several barriers and have listed potential solutions that may improve recruitment and lead to fewer dropouts in trials involving older populations. Implementation of our findings may help mitigate the manifold challenges that come with running a trial with older people

<b>Paradoxically protective effect of glucocorticoids on bone mass and fragility fracture in a large cohort: a cross-sectional</b> <b>study</b>.

ObjectivesGlucocorticoids (GCs) increase the risk of fracture through reduction in BMD; they may also reduce bone quality, but recent supporting data are scarce. We aimed to confirm these effects in a large population-based cohort.MethodsWe used data from patients referred for first hip and lumbar spine BMD estimation by the sole DXA scanner in the north-west of England between June 2004 and September 2016. We compared the history of fractures and BMD between patients currently on GCs and patients never exposed to GC. A logistic model adjusted for possible confounders.ResultsMore than 20 000 subjects were included, 82% female, with mean age 63 (s.d. 13) years; 19% were currently on GCs. The patients on GCs were more often male, with higher BMI, but their age was similar to those not exposed to GC. Surprisingly, patients receiving GCs had ∼2% higher BMD at both sites (P vs 34%; P ConclusionIn this large population-based cohort, current GC use compared with never use was associated with higher bone mass and fewer rather than more fractures after adjusting for confounders. These results might be subject to unmeasured confounding, but for now they do not lend support to a detrimental effect of GCs on bone

Outcome measures in rheumatoid arthritis randomised trials over the last 50 years

BACKGROUND: The development and application of standardised sets of outcomes to be measured and reported in clinical trials have the potential to increase the efficiency and value of research. One of the most notable of the current outcome sets began nearly 20 years ago: the World Health Organization and International League of Associations for Rheumatology core set of outcomes for rheumatoid arthritis clinical trials, originating from the OMERACT (Outcome Measures in Rheumatology) Initiative. This study assesses the use of this core outcome set by randomised trials in rheumatology. METHODS: An observational review was carried out of 350 randomised trials for the treatment of rheumatoid arthritis identified through The Cochrane Library (up to and including September 2012 issue). Reports of these trials were evaluated to determine whether or not there were trends in the proportion of trials reporting on the full set of core outcomes over time. Researchers who conducted trials after the publication of the core set were contacted to assess their awareness of it and to collect reasons for non-inclusion of the full core set of outcomes in the study. RESULTS: Since the introduction of the core set of outcomes for rheumatoid arthritis, the consistency of measurement of the core set of outcomes has improved, although variation in the choice of measurement instrument remains. The majority of trialists who responded said that they would consider using the core outcome set in the design of a new trial. CONCLUSIONS: This observational review suggests that a higher percentage of trialists conducting trials in rheumatoid arthritis are now measuring the rheumatoid arthritis core outcome set. Core outcome sets have the potential to improve the evidence base for health care, but consideration must be given to the methods for disseminating their availability amongst the relevant communities

OMERACT: An international initiative to improve outcome measurement in rheumatology

OMERACT is the acronym for an international, informally organized network initiated in 1992 aimed at improving outcome measurement in rheumatology. Chaired by an executive committee, it organizes consensus conferences in a 2-yearly cycle that circles the globe. Data driven recommendations are prepared and updated by expert working groups. Recommendations include core sets of measures for most of the major rheumatologic conditions. Since 2002 patients have been actively engaged in the process

Association Between Participant Retention and the Proportion of Included Elderly People in Rheumatology Trials: Results From a Series of Exploratory Meta‐Regression Analyses

Objective. The elderly, a population defined by an age of ≥65 years, are underrepresented in rheumatology trials, possibly due to investigators' concerns of increased premature discontinuations in higher age groups. The present study was undertaken to evaluate whether the proportion of included elderly individuals (PE) is independently associated with participant retention in rheumatology trials. Methods. Medline was searched for randomized controlled trials (RCTs) in rheumatoid arthritis (RA) and osteoarthritis (OA) of any intervention (years 2016 and 2017). PE was either extracted from the research manuscript or estimated from an assumed (truncated) normal distribution. We used mixed-effects meta-regression models including several covariates to assess whether there is an independent association between PE and participant retention. Using sensitivity analyses, we evaluated whether associations were connected to attrition due to lack of efficacy (LoE) or adverse events (AE). Results. In total, 243 RCTs comprising >48,000 participants were included. Pooled participant retention was 88%. PE was not associated with retention in the unadjusted (P = 0.97) or adjusted (all: P ≥0.14) models. Of all covariates, only study duration and type of intervention were associated with retention (both: P < 0.001). Post hoc analyses allowing for interaction revealed a small but statistically significant positive association between PE and retention in pharmacologic interventions and a negative association in physical/physiotherapeutic interventions (overall P for interaction = 0.05). No associations were found for PE and attrition due to LoE or AE. Conclusion. Participant retention in RA and OA trials is high and not associated with PE. These findings should motivate investigators to include more elderly participants in rheumatology trials

Measurement Properties of Visual Analogue Scale, Numeric Rating Scale, and Pain Severity Subscale of the Brief Pain Inventory in Patients With Low Back Pain:A Systematic Review

Visual Analogue Scale (VAS), Numeric Rating Scale (NRS), and Pain Severity subscale of the Brief Pain Inventory (BPI-PS)] are the most frequently used instruments to measure pain intensity in low back pain (LBP). However, their measurement properties in this population have not been systematically reviewed. The goal of this study was to provide such systematic evidence synthesis. Six electronic sources (MEDLINE, EMBASE, CINAHL, PsycINFO, SportDiscus, Google Scholar) were searched (July 2017). Studies assessing any measurement property in patients with non-specific LBP were included. Two reviewers independently screened articles and assessed risk of bias using the COSMIN checklist. For each measurement property: evidence quality was rated as high, moderate, low, or very low (GRADE approach); results were classified as sufficient, insufficient or inconsistent. Ten studies assessed the VAS, 13 the NRS, four the BPI-PS. The three instruments displayed low or very low quality evidence for content validity. High quality evidence was only available for NRS insufficient measurement error. Moderate evidence was available for: NRS inconsistent responsiveness, BPI-PS sufficient structural validity and internal consistency, and BPI-PS inconsistent construct validity. All VAS measurement properties were underpinned by no, low or very low quality evidence, likewise the other measurement properties of NRS and BPI-PS

PROMIS Physical Function short forms display item- and scale-level characteristics at least as good as the Roland Morris Disability Questionnaire in patients with chronic low back pain

OBJECTIVE: To compare dimensionality, item-level characteristics, scale-level reliability and construct validity of PROMIS® Physical Function short forms (PROMIS-PF) and 24-item Roland Morris Disability Questionnaire (RMDQ-24) in patients with chronic low back pain (LBP). DESIGN: Cross-sectional study. SETTING: Secondary care center for rehabilitation and rheumatology. PARTICIPANTS: Patients with non-specific LBP ≥ 3 months (n = 768). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Dutch versions of the 4-, 6-, 8-, 10- and 20-item PROMIS-PF, and of the RMDQ-24. RESULTS: Mean age was 49 years (±13), 77% female, 54% displayed pain for more than 5 years. PROMIS-PF-6, PROMIS-PF-8 and RMDQ-24 exhibited sufficient unidimensionality (confirmatory factor analysis: CFI >0.950, TLI >0.950 and RMSEA 0.001). Two-parameter item response theory models found two items with low discrimination for RMDQ-24. All other instruments had adequate fit statistics and item parameters. PROMIS-PF-20 displayed the best scale-level reliability. Construct validity was sufficient for all instruments as all hypotheses on expected correlations with other instruments, and differences between relevant subgroups, were met. CONCLUSIONS: PROMIS-PF-6, PROMIS-PF-8 and RMDQ-24 exhibited better unidimensionality, whereas PROMIS-PF-4, PROMIS-PF-6 PROMIS-PF-8 and PROMIS-PF-10 showed superior item-level characteristics. PROMIS-PF-20 was the instrument with the best scale-level reliability. This study warrants assessment of other measurement properties of PROMIS-PF short forms in comparison to disease-specific physical functioning instruments in LBP

Instrument Selection Using the OMERACT Filter 2.1: The OMERACT Methodology.

Objective: Outcome Measures in Rheumatology (OMERACT) Filter 2.1 revised the process used for core outcome measurement set selection to add rigour and transparency in decision making. This paper describes OMERACT’s methodology for instrument selection. Methods: We presented instrument selection processes, tools, and reporting templates at OMERACT 2018, introducing the concept of “3 pillars, 4 questions, 7 measurement properties, 1 answer”. Truth, Discrimination and Feasibility are the three original OMERACT pillars. Based on these, we developed four signaling questions. We introduced the Summary of Measurement Properties (SOMP) table which summarizes the seven measurement properties: Truth (domain match, construct validity), Discrimination (test-retest reliability, longitudinal construct validity (responsiveness), clinical trial discrimination, thresholds of meaning), and Feasibility. These properties address a set of standards which, when met, answer the one question: Is there enough evidence to support the use of this instrument in clinical research of the benefits and harms of treatments in the population and study setting described? The OMERACT Filter 2.1 was piloted on two instruments by the Psoriatic Arthritis Working Group Results: The methodology was reviewed in a full plenary session and facilitated breakout groups. Tools to facilitate retention of the process (i.e., “The OMERACT Way”) were provided. The two instruments were presented and the recommendation of the working group was endorsed in the first OMERACT Filter 2.1 Instrument Selection votes. Conclusion: Instrument Selection using OMERACT Filter 2.1 is feasible and is now being implemented

External Validation of a Measurement Tool to Assess Systematic Reviews (AMSTAR)

BACKGROUND: Thousands of systematic reviews have been conducted in all areas of health care. However, the methodological quality of these reviews is variable and should routinely be appraised. AMSTAR is a measurement tool to assess systematic reviews. METHODOLOGY: AMSTAR was used to appraise 42 reviews focusing on therapies to treat gastro-esophageal reflux disease, peptic ulcer disease, and other acid-related diseases. Two assessors applied the AMSTAR to each review. Two other assessors, plus a clinician and/or methodologist applied a global assessment to each review independently. CONCLUSIONS: The sample of 42 reviews covered a wide range of methodological quality. The overall scores on AMSTAR ranged from 0 to 10 (out of a maximum of 11) with a mean of 4.6 (95% CI: 3.7 to 5.6) and median 4.0 (range 2.0 to 6.0). The inter-observer agreement of the individual items ranged from moderate to almost perfect agreement. Nine items scored a kappa of >0.75 (95% CI: 0.55 to 0.96). The reliability of the total AMSTAR score was excellent: kappa 0.84 (95% CI: 0.67 to 1.00) and Pearson's R 0.96 (95% CI: 0.92 to 0.98). The overall scores for the global assessment ranged from 2 to 7 (out of a maximum score of 7) with a mean of 4.43 (95% CI: 3.6 to 5.3) and median 4.0 (range 2.25 to 5.75). The agreement was lower with a kappa of 0.63 (95% CI: 0.40 to 0.88). Construct validity was shown by AMSTAR convergence with the results of the global assessment: Pearson's R 0.72 (95% CI: 0.53 to 0.84). For the AMSTAR total score, the limits of agreement were -0.19+/-1.38. This translates to a minimum detectable difference between reviews of 0.64 'AMSTAR points'. Further validation of AMSTAR is needed to assess its validity, reliability and perceived utility by appraisers and end users of reviews across a broader range of systematic reviews