Are older adults insufficiently included in clinical trials?-An umbrella review.
drug discovery and development
gerontopharmacology
good clinical practice
pharmacoepidemiology
randomized controlled trial
risk assessment
safety pharmacology
Journal
Basic & clinical pharmacology & toxicology
ISSN: 1742-7843
Titre abrégé: Basic Clin Pharmacol Toxicol
Pays: England
ID NLM: 101208422
Informations de publication
Date de publication:
Feb 2021
Feb 2021
Historique:
received:
24
05
2020
revised:
13
11
2020
accepted:
13
11
2020
pubmed:
20
11
2020
medline:
28
7
2021
entrez:
19
11
2020
Statut:
ppublish
Résumé
Treatment guidelines are primarily based on randomized clinical trials (RCTs). RCTs tend to some extent to exclude older adults despite the fact that physicians need guidance when treating this patient group. By summarizing existing literature, we aimed to (a) quantify the proportion of RCTs and other clinical studies (CTs) that did not adequately include older adults; (b) identify the main barriers for this non-inclusion; and (c) identify suggested solution for inclusion of older adults in RCTs and other CTs. In this umbrella review, Embase and PubMed were searched for relevant papers, and 2701 papers were identified. The subsequent screening resulted in 22 papers. The Critical Appraisal Skills Program was used as quality assessment tool to evaluate these 22 papers. We found that: (a) The most frequent outcome designating missing inclusion of older adults was the use of age limit as exclusion criterion in studies-the proportion of this was 10%-60%; (b) barriers for inclusion were mainly exclusion criteria, logistic challenges and financial constraints; and (c) more extensive inclusion would require more explicit inclusion criteria, merely application of exclusion criteria when absolutely needed, change of researchers' attitude, further inclusion of supporting relatives to overcome the logistical challenges and more financial funding.
Types de publication
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
213-223Informations de copyright
© 2020 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).
Références
Economic NUDoI, Division SAP, Unidas N, Economic UNDo, population NUDdl. World Population to 2300. United Nations Publications, 2004.
Marengoni A, Angleman S, Melis R, et al. Aging with multimorbidity: a systematic review of the literature. Ageing Res Rev. 2011;10(4):430-439.
Lernfelt B, Samuelsson O, Skoog I, Landahl S. Changes in drug treatment in the elderly between 1971 and 2000. Eur J Clin Pharmacol. 2003;59(8-9):637-644.
Garfield FB, Garfield JM. Clinical judgment and clinical practice guidelines. Int J Technol Assessment Health Care. 2000;16(04):1050-1060.
Zulman DM, Sussman JB, Chen X, Cigolle CT, Blaum CS, Hayward RA. Examining the evidence: a systematic review of the inclusion and analysis of older adults in randomized controlled trials. J Gen Intern Med. 2011;26(7):783-790.
Singh S, Bajorek B. Pharmacotherapy in the ageing patient: The impact of age per se (A review). Ageing Res Rev. 2015;24(Pt B):99-110.
Shepherd AM, Hewick DS, Moreland TA, Stevenson IH. Age as a determinant of sensitivity to warfarin. Br J Clin Pharmacol. 1977;4(3):315-320.
Gurwitz JH, Col NF, Avorn J. The exclusion of the elderly and women from clinical trials in acute myocardial infarction. JAMA. 1992;268(11):1417-1422.
Aromataris E, Fernandez R, Godfrey CM, Holly C, Khalil H, Tungpunkom P. Summarizing systematic reviews: methodological development, conduct and reporting of an umbrella review approach. Int J Evid Based Healthcare. 2015;13(3):132-140.
Methley AM, Campbell S, Chew-Graham C, McNally R, Cheraghi-Sohi S. PICO, PICOS and SPIDER: a comparison study of specificity and sensitivity in three search tools for qualitative systematic reviews. BMC Health Services Res. 2014;14:579.
Woodall A, Morgan C, Sloan C, Howard L. Barriers to participation in mental health research: are there specific gender, ethnicity and age related barriers? BMC Psychiatry. 2010;10(1):103.
Akobeng AK. Principles of evidence based medicine. Arch Dis Childhood. 2005;90(8):837-840.
Cruz-Jentoft AJ, Gutierrez B. Upper age limits in studies submitted to a research ethics committee. Aging Clin Exp Res. 2010;22(2):175-178.
Dodd KS, Saczynski JS, Zhao Y, Goldberg RJ, Gurwitz JH. Exclusion of older adults and women from recent trials of acute coronary syndromes. J Am Geriatr Soc. 2011;59(3):506-511.
Avni T, Shiver-Ofer S, Leibovici L, et al. Participation of elderly adults in randomized controlled trials addressing antibiotic treatment of pneumonia. J Am Geriatr Soc. 2015;63(2):233-243.
Desmarais P, Miville C, Milan-Tomas A, et al. Age representation in antiepileptic drug trials: A systematic review and meta-analysis. Epilepsy Res. 2018;142:9-15.
Gouverneur A, Salvo F, Berdai D, Moore N, Fourrier-Reglat A, Noize P. Inclusion of elderly or frail patients in randomized controlled trials of targeted therapies for the treatment of metastatic colorectal cancer: A systematic review. J Geriatr Oncol. 2018;9(1):15-23.
Bellera C, Praud D, Petit-Moneger A, McKelvie-Sebileau P, Soubeyran P, Mathoulin-Pelissier S. Barriers to inclusion of older adults in randomised controlled clinical trials on Non-Hodgkin's lymphoma: A systematic review. Cancer Treatment Rev. 2013;39(7):812-817.
Hamaker ME, Stauder R, van Munster BC. Exclusion of older patients from ongoing clinical trials for hematological malignancies: an evaluation of the National Institutes of Health Clinical Trial Registry. Oncologist. 2014;19(10):1069-1075.
Thake M, Lowry A. A systematic review of trends in the selective exclusion of older participant from randomised clinical trials. Arch Gerontol Geriatr. 2017;72:99-102.
Hori A, Shibata T, Kami M, et al. Age disparity between a cancer population and participants in clinical trials submitted as a new drug application of anticancer drugs in Japan. Cancer. 2007;109(12):2541-2546.
Jennens RR, Giles GG, Fox RM. Increasing underrepresentation of elderly patients with advanced colorectal or non-small-cell lung cancer in chemotherapy trials. Intern Med J. 2006;36(4):216-220.
Townsley CA, Selby R, Siu LL. Systematic review of barriers to the recruitment of older patients with cancer onto clinical trials. J Clin Oncol. 2005;23(13):3112-3124.
Ridda I, MacIntyre CR, Lindley RI, Tan TC. Difficulties in recruiting older people in clinical trials: an examination of barriers and solutions. Vaccine. 2010;28(4):901-906.
Kennedy-Martin T, Curtis S, Faries D, Robinson S, Johnston J. A literature review on the representativeness of randomized controlled trial samples and implications for the external validity of trial results. Trials. 2015;16:495.
Bayer A, Fish M. The doctor's duty to the elderly patient in clinical trials. Drugs Aging. 2003;20(15):1087-1097.
Kazmierska J. Do we protect or discriminate? Representation of senior adults in clinical trials. Rep Pract Oncol Radiother. 2012;18(1):6-10.
Witham MD, McMurdo ME. How to get older people included in clinical studies. Drugs Aging. 2007;24(3):187-196.
Denson AC, Mahipal A. Participation of the elderly population in clinical trials: barriers and solutions. Cancer Control. 2014;21(3):209-214.
Vitale C, Fini M, Spoletini I, Lainscak M, Seferovic P, Rosano GM. Under-representation of elderly and women in clinical trials. Int J Cardiol. 2017;232:216-221.
Lewis JH, Kilgore ML, Goldman DP, et al. Participation of patients 65 years of age or older in cancer clinical trials. J Clin Oncol. 2003;21(7):1383-1389.
Bajorek B, Krass I, Ogle S, Duguid M, Shenfield G. The impact of age on antithrombotic use in elderly patients with non-valvular atrial fibrillation. Australasian J Ageing. 2002;21(1):36-41.
Pugh D, Pugh J, Mead GE. Attitudes of physicians regarding anticoagulation for atrial fibrillation: a systematic review. Age Ageing. 2011;40(6):675-683.
Petty DR, Zermansky AG, Raynor DK, et al. "No thank you": why elderly patients declined to participate in a research study. Pharmacy World Sci. 2001;23(1):22-27.
Adams J, Silverman M, Musa D, Peele P. Recruiting older adults for clinical trials. Control Clin Trials. 1997;18(1):14-26.
Harari S. Randomised controlled trials and real-life studies: two answers for one question. Eur Respir Rev. 2018;27(149):180080.
Dunn C, Wilson A, Sitas F. Older cancer patients in cancer clinical trials are underrepresented. Systematic literature review of almost 5000 meta- and pooled analyses of phase III randomized trials of survival from breast, prostate and lung cancer. Cancer Epidemiol. 2017;51:113-117.