Association Between Participant Retention and the Proportion of Included Elderly People in Rheumatology Trials: Results From a Series of Exploratory Meta-Regression Analyses.
Journal
Arthritis care & research
ISSN: 2151-4658
Titre abrégé: Arthritis Care Res (Hoboken)
Pays: United States
ID NLM: 101518086
Informations de publication
Date de publication:
10 2020
10 2020
Historique:
received:
21
03
2019
accepted:
13
08
2019
pubmed:
20
8
2019
medline:
28
11
2020
entrez:
18
8
2019
Statut:
ppublish
Résumé
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. 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). 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. 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.
Types de publication
Journal Article
Meta-Analysis
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1490-1496Informations de copyright
© 2019 The Authors. Arthritis Care & Research published by Wiley Periodicals, Inc. on behalf of American College of Rheumatology.
Références
Palmowski A, Buttgereit T, Palmowski Y, Nielsen SM, Boers M, Christensen R, et al. 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. Semin Arthritis Rheum 2019;48:983-9.
Sera LC, McPherson ML. Pharmacokinetics and pharmacodynamic changes associated with aging and implications for drug therapy. Clin Geriatr Med 2012;28:273-86.
Hohl CM, Dankoff J, Colacone A, Afilalo M. Polypharmacy, adverse drug-related events, and potential adverse drug interactions in elderly patients presenting to an emergency department. Ann Emerg Med 2001;38:666-71.
Salive ME. Multimorbidity in older adults. Epidemiol Rev 2013;35:75-83.
Budnitz DS, Lovegrove MC, Shehab N, Richards CL. Emergency hospitalizations for adverse drug events in older Americans. N Engl J Med 2011;365:2002-12.
Daien CI, Morel J. Predictive factors of response to biological disease modifying antirheumatic drugs: towards personalized medicine. Mediators Inflamm 2014;2014:386148.
Yamanaka H, Tanaka Y, Inoue E, Hoshi D, Momohara S, Hanami K, et al. Efficacy and tolerability of tocilizumab in rheumatoid arthritis patients seen in daily clinical practice in Japan: results from a retrospective study (REACTION study). Mod Rheumatol 2011;21:122-33.
Dalal DS, Duran J, Brar T, Alqadi R, Halladay C, Lakhani A, et al. Efficacy and safety of biological agents in the older rheumatoid arthritis patients compared to young: a systematic review and meta-analysis. Semin Arthritis Rheum 2019;48:799-807.
Van Spall HC, Toren A, Kiss A, Fowler RA. Eligibility criteria of randomized controlled trials published in high-impact general medical journals: a systematic sampling review. JAMA 2007;297:1233-40.
Cherubini A, Oristrell J, Pla X, Ruggiero C, Ferretti R, Diestre G, et al. The persistent exclusion of older patients from ongoing clinical trials regarding heart failure. Arch Intern Med 2011;171:550-6.
Cross M, Smith E, Hoy D, Carmona L, Wolfe F, Vos T, et al. The global burden of rheumatoid arthritis: estimates from the global burden of disease 2010 study. Ann Rheum Dis 2014;73:1316-22.
Cross M, Smith E, Hoy D, Nolte S, Ackerman I, Fransen M, et al. The global burden of hip and knee osteoarthritis: estimates from the global burden of disease 2010 study. Ann Rheum Dis 2014;73:1323-30.
Helmick CG, Felson DT, Lawrence RC, Gabriel S, Hirsch R, Kwoh CK, et al. Estimates of the prevalence of arthritis and other rheumatic conditions in the United States. Part I. Arthritis Rheum 2008;58:15-25.
Lawrence RC, Felson DT, Helmick CG, Arnold LM, Choi H, Deyo RA, et al. Estimates of the prevalence of arthritis and other rheumatic conditions in the United States. Part II. Arthritis Rheum 2008;58:26-35.
Woolf AD, Pfleger B. Burden of major musculoskeletal conditions. Bull World Health Organ 2003;81:646-56.
Crowson CS, Matteson EL, Myasoedova E, Michet CJ, Ernste FC, Warrington KJ, et al. The lifetime risk of adult-onset rheumatoid arthritis and other inflammatory autoimmune rheumatic diseases. Arthritis Rheum 2011;63:633-9.
Hartman L, Rasch LA, Klausch T, Bijlsma HW, Christensen R, Smulders YM, et al. Harm, benefit and costs associated with low-dose glucocorticoids added to the treatment strategies for rheumatoid arthritis in elderly patients (GLORIA trial): study protocol for a randomised controlled trial. Trials 2018;19:67.
Moher D, Liberati A, Tetzlaff J, Altman DG. PRISMA Group. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. Ann Intern Med 2009;151:264-9, w64.
Higgins JP, Green S. Cochrane handbook for systematic reviews of interventions version 5.1. The Cochrane Collaboration; 2011. URL: www.cochrane-handbook.org.
Konrat C, Boutron I, Trinquart L, Auleley GR, Ricordeau P, Ravaud P. Underrepresentation of elderly people in randomised controlled trials: the example of trials of 4 widely prescribed drugs. PLoS ONE 2012;7:e33559.
Bourgeois FT, Orenstein L, Ballakur S, Mandl KD, Ioannidis JP. Exclusion of elderly people from randomized clinical trials of drugs for ischemic heart disease. J Am Geriatr Soc 2017;65:2354-61.
Viechtbauer W. Conducting meta-analyses in R with the Metafor package. J Stat Softw 2010;36:48.
Thompson SG, Higgins JP. How should meta-regression analyses be undertaken and interpreted? Stat Med 2002;21:1559-73.
Denson AC, Mahipal A. Participation of the elderly population in clinical trials: barriers and solutions. Cancer Control 2014;21:209-14.
Carroll CB, Zajicek JP. Designing clinical trials in older people. Maturitas 2011;68:337-41.
Basche M, Barón AE, Eckhardt SG, Balducci L, Persky M, Levin A, et al. Barriers to enrollment of elderly adults in early-phase cancer clinical trials. J Oncol Pract 2008;4:162-8.
Cruz-Jentoft AJ, Carpena-Ruiz M, Montero-Errasquín B, Sánchez-Castellano C, Sánchez-García E. Exclusion of older adults from ongoing clinical trials about type 2 diabetes mellitus. J Am Geriatr Soc 2013;61:734-8.
Liberopoulos G, Trikalinos NA, Ioannidis JP. The elderly were under-represented in osteoarthritis clinical trials. J Clin Epidemiol 2009;62:1218-23.
Chatfield MD, Brayne CE, Matthews FE. A systematic literature review of attrition between waves in longitudinal studies in the elderly shows a consistent pattern of dropout between differing studies. J Clin Epidemiol 2005;58:13-9.
Warner ET, Glasgow RE, Emmons KM, Bennett GG, Askew S, Rosner B, et al. Recruitment and retention of participants in a pragmatic randomized intervention trial at three community health clinics: results and lessons learned. BMC Public Health 2013;13:192.
Kempen GI, van Sonderen E. Psychological attributes and changes in disability among low-functioning older persons: does attrition affect the outcomes? J Clin Epidemiol 2002;55:224-9.
Spiers S, Oral E, Fontham ET, Peters ES, Mohler Bensen JT, et al. Modelling attrition and nonparticipation in a longitudinal study of prostate cancer. BMC Med Res Methodol 2018;18:60.
Iannaccone CK, Fossel A, Tsao H, Cui J, Weinblatt M, Shadick N. Factors associated with attrition in a longitudinal rheumatoid arthritis registry. Arthritis Care Res (Hoboken) 2013;65:1183-9.
Castillo M. Is your journal indexed in MEDLINE? AJNR Am J Neuroradiol 2011;32:1-2.