Appraising clinical applicability of studies: mapping and synthesis of current frameworks, and proposal of the FrACAS framework and VICORT checklist.

BACKGROUND: Not all research findings are translated to clinical practice. Reasons for lack of applicability are varied, and multiple frameworks and criteria exist to appraise the general applicability of epidemiological and clinical research. In this two-part study, we identify, map, and synthesize frameworks and criteria; we develop a framework to assist clinicians to appraise applicability specifically from a clinical perspective. METHODS: We conducted a literature search in PubMed and Embase to identify frameworks appraising applicability of study results. Conceptual thematic analysis was used to synthesize frameworks and criteria. We carried out a framework development process integrating contemporary debates in epidemiology, findings from the literature search and synthesis, iterative pilot-testing, and brainstorming and consensus discussions to propose a concise framework to appraise clinical applicability. RESULTS: Of the 4622 references retrieved, we identified 26 unique frameworks featuring 21 criteria. Frameworks and criteria varied by scope and level of aggregation of the evidence appraised, target user, and specific area of applicability (internal validity, clinical applicability, external validity, and system applicability). Our proposed Framework Appraising the Clinical Applicability of Studies (FrACAS) classifies studies in three domains (research, practice informing, and practice changing) by examining six criteria sequentially: Validity, Indication-informativeness, Clinical relevance, Originality, Risk-benefit comprehensiveness, and Transposability (VICORT checklist). CONCLUSIONS: Existing frameworks to applicability vary by scope, target user, and area of applicability. We introduce FrACAS to specifically assess applicability from a clinical perspective. Our framework can be used as a tool for the design, appraisal, and interpretation of epidemiological and clinical studies.

The state of frailty in research: A mapping review of its clinical applicability to practice.

Research on frailty has expanded in the last decade, but direct evidence supporting its implementation in clinical practice may be limited. This mapping review synthesizes the contexts-of-use and overall clinical applicability of recent pre-COVID frailty research. We sampled 476 articles from articles published on frailty in PubMed and EMBASE in 2017-2018, of which 150 articles were fully appraised for the contexts-of-use, definitions, and interventions. A clinical applicability framework was used to classify articles as practice-changing, practice-informing, or not practice-informing. Of the 476 sampled articles, 31% (n = 150) used frailty in functions that could inform a clinical indication: predictor or mediator (26%, n = 125), selection criterion (3%, n = 15), and effect modifier (2%, n = 10). Articles spanned all health disciplines, and cohort studies comprised 91% (n = 137) of studies and trials 9% (n = 13). Thirty-eight frailty definitions using varied cut-offs and a wide range of interventions were identified. Among all articles, 13% (n = 63) of articles were practice-informing, 2% (n = 11) potentially practice-changing, and 0.2% (n = 1) clearly practice-changing. Lack of well-defined intervention and identifiable effect (96%) or originality (83%) were predominant reasons reducing applicability. Only a minority of recent frailty research provides direct evidence of applicability to practice. Future research on frailty should focus on translating frailty, as a risk factor, into a clinical indication and address definition ambiguity.

Clinical Correlates and Implications of the Reliability of the Frailty Index in the Canadian Longitudinal Study on Aging.

BACKGROUND: Deficit accumulation frailty indices (FIs) are widely used to characterize frailty. FIs vary in number and composition of items; the impact of this variation on reliability and clinical applicability is unknown. METHOD: We simulated 12 000 studies using a set of 70 candidate deficits in 12 080 community-dwelling participants 65 years and older. For each study, we varied the number (5, 10, 15, 25, 35, 45) and composition (random selection) of items defining the FI and calculated descriptive and predictive estimates: frailty score, prevalence, frailty cutoff, mortality odds ratio, predicted probability of mortality for FI = 0.28 (prevalence threshold), and FI cutoff predicting 10% mortality over the follow-up. We summarized the estimates' medians and spreads (0.025-0.975 quantiles) by number of items and calculated intraclass correlation coefficients (ICCs). RESULTS: Medians of frailty scores were 0.11-0.12 with decreasing spreads from 0.04-0.24 to 0.10-0.14 for 5-item and 45-item FIs. The median cutoffs identifying 15% as frail was 0.19-0.20 and stable; the spreads decreased with more items. However, medians and spreads for the prevalence of frailty (median: 11%-3%), mortality odds ratio (median: 1.24-2.19), predicted probability of mortality (median: 8%-17%), and FI cutoff predicting 10% mortality (median: 0.38-0.20) varied markedly. ICC increased from 0.19 (5-item FIs) to 0.84 (45-item FIs). CONCLUSIONS: Variability in the number and composition of items of individual FIs strongly influences their reliability. Estimates using FIs may not be sufficiently stable for generalizing results or direct application. We propose avenues to improve the development, reporting, and interpretation of FIs.

Health Heterogeneity in Older Adults: Exploration in the Canadian Longitudinal Study on Aging.

BACKGROUND: A widely held dictum in aging research is that heterogeneity in health increases with age, but the basis for this claim has not been fully investigated. We examined heterogeneity at different ages across health characteristics to describe variation and trends; we investigated the comparative importance of between-age versus within-age heterogeneity. DESIGN: This was a cohort study. SETTING: Community-dwelling older adults. PARTICIPANTS: A total of 30,097 adults aged 45 to 86 years, from the Canadian Longitudinal Study on Aging, were included. MEASUREMENTS: Thirty-four health characteristics in eight domains (physical measures, vital signs, physiological measures, physical performance, function/disability, chronic conditions, frailty, laboratory values) were assessed cross-sectionally. We used regression models to examine heterogeneity in health characteristics (using absolute deviation) and domains (using effective variance) in relation to age. Comparison between between-age and within-age heterogeneity was quantified by estimating the age threshold at which the former exceeds the latter. RESULTS: Of the 34 health characteristics, 17 showed increased heterogeneity, 8 decreased, and 9 no association with age. The associations between heterogeneity and age increased generally but were nonlinear for most domains and nonmonotonic for some. We observed peak heterogeneity at approximately 70 years. Between-age heterogeneity, compared with within-age heterogeneity, was most important for forced expiratory volume in 1 second and grip strength but varied across characteristics. CONCLUSION: Overall health heterogeneity increases with age but does not uniformly increase across all variables and domains. Heterogeneity in aging reinforces the need for geriatric assessment and personalized care, depending on which health characteristics are assessed, their measurement properties, and their referent group. Our findings suggest further research to develop improved single-dimension and multidimensional instruments, as well as specific vital and laboratory reference ranges for older adults.