Abstract
To examine how target patients seen in clinical practice are represented in clinical trials for approved drugs in Japan, we compared the age distribution of older patients enrolled in confirmatory clinical trials for regulatory approval with that of the estimated actual patient population. Drugs for 6 chronic conditions common among older patients (diabetes mellitus, hypertension, rheumatoid arthritis, non-small cell lung cancer, depression and Alzheimer’s disease) launched by 2012 in Japan were selected. The disparity in age distribution between patients in trials and patients seen in clinical practice varied depending on the disease, but older patients, especially those aged 75 or older, were generally underrepresented in clinical trials for regulatory approval in Japan. Under-representation of older patients in hypertension trials was particularly marked compared to other conditions, despite the similarity in age distribution of patients seen in clinical practice. One factor causing this disparity may be an upper age limit in clinical trial protocols. More effort is needed to properly characterize the benefits and risks of drugs for older patients. This should include the active enrollment of older patients in clinical trials, the establishment of better assessment tools such as pharmacometric approaches, and the appropriate planning and conducting of post-marketing surveys and studies.
Similar content being viewed by others
References
United Nations, Department of Economic and Social Affairs, Population Division, 2011. World Population Prospects: The 2010 Revision, CD-ROM Edition. http://esa.un.org/wpp/Excel-Data/DB02_Stock_Indicators/WPP2010_DB2_F05_3A_OLD_AGE_DEPENDENCY_RATIO_1564.XLS. Accessed 19 August 2013.
Cabinet Office. [White paper on aging society (In Japanese)]. http://www8.cao.go.jp/kourei/whitepaper/w-2012/zenbun/24pdf_index.html. Accessed 19 August 2013.
Corsonello A, Pedone C, Incalzi RA. Age-related pharmacokinetic and pharmacodynamic changes and related risk of adverse drug reactions. Curr Med Chem 2010;17:571–84.
Bowie MW, Slattum PW. Pharmacodynamics in older adults: a review. Am J Geriatr Pharmacother 2007;5:263–303.
Indications for fibrinolytic therapy in suspected acute myocardial infarction: collaborative overview of early mortality and major morbidity results from all randomised trials of more than 1000 patients. Fibrinolytic Therapy Trialists’ (FTT) Collaborative Group. Lancet 1994;343:311–22.
Yusuf S, Zhao F, Mehta SR, Chrolavicius S, Tognoni G, Fox KK. Effects of clopidogrel in addition to aspirin in patients with acute coronary syndromes without ST-segment elevation. N Engl J Med 2001;345:494–502.
Clegg A, Young J, Iliffe S, Rikkert MO, Rockwood K. Frailty in elderly people. Lancet 2013;381:752–62.
Information on proper use of Visiclear Combination Tablets. September 2012; http://www.info.pmda.go.jp/iyaku_info/file/kigyo_oshirase_201202_3.pdf.
Thiemann DR, Coresh J, Schulman SP, Gerstenblith G, Oetgen WJ, Powe NR. Lack of benefit for intravenous thrombolysis in patients with myocardial infarction who are older than 75 years. Circulation 2000;101:2239–2246.
Hylek EM, Evans-Molina C, Shea C, Henault LE, Regan S. Major hemorrhage and tolerability of warfarin in the first year of therapy among elderly patients with atrial fibrillation. Circulation 2007;115:2689–2696.
Gurwitz JH, Col NF, Avorn J. The exclusion of the elderly and women from clinical trials in acute myocardial infarction. JAMA 1992;268:1417–1422.
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;59:506–511.
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;26:783–790.
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;171:550–556.
Gill SS, Bronskill SE, Mamdani M, Sykora K, Li P, Shulman KI, et al. Representation of patients with dementia in clinical trials of donepezil. Can J Clin Pharmacol 2004;11:e274–e285.
Murthy VH, Krumholz HM, Gross CP. Participation in cancer clinical trials: race-, sex-, and age-based disparities. JAMA 2004;291:2720–2726.
European Medicines Agency, Concept paper on the need for a reflection paper on quality aspects of medicines for older people 2013.
Diener L, Hugonot-Diener L, Alvino S, Baeyens JP, Bone MF, Chirita D, et al. Guidance synthesis. Medical research for and with older people in Europe: proposed ethical guidance for good clinical practice: ethical considerations. The journal of nutrition, health & aging 2013;17:625–627.
Vellas B, Pahor M, Manini T, Rooks D, Guralnik JM, Morley J, et al. Designing pharmaceutical trials for sarcopenia in frail older adults: EU/US Task Force recommendations. The journal of nutrition, health & aging 2013;17:612–618.
Ministry of Health, Labour and Welfare, 2011. Patient Survey. http://www.estat.go.jp/SG1/estat/GL08020101.do?_toGL08020101_&tstatCode=000001031167&requestSender=dsearch. Accessed 19 August 2013.
Nissen SE, Wolski K. Effect of rosiglitazone on the risk of myocardial infarction and death from cardiovascular causes. N Engl J Med 2007;356:2457–2471.
ICH Harmonized Tripartite Guideline. Studies in Support of special populations: GERIATRICS E7 1993. http://www.ich.org/fileadmin/Public_Web_Site/ICH_Products/Guidelines/Efficacy/E7/Step4/E7_Guideline.pdf. Accessed 19 August 2013.
Manolis E, Osman TE, Herold R, Koenig F, Tomasi P, Vamvakas S, et al. Role of modeling and simulation in pediatric investigation plans. Paediatr Anaesth 2011;21:214–221.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Asahina, Y., Sugano, H., Sugiyama, E. et al. Representation of older patients in clinical trials for drug approval in Japan. J Nutr Health Aging 18, 520–523 (2014). https://doi.org/10.1007/s12603-014-0031-5
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12603-014-0031-5