Clinical trials in geriatrics: actual status and international regulatory guidlines
https://doi.org/10.37586/2686-8636-1-2021-97-104
Abstract
The number of old and very old people is increasing every year. Geriatric population is considered as the most growing age group. By different estimations about 60% of medicines are prescribed to patients of 65 and older. In the same time this age group is underrepresented in clinical trials. Participation of elderlies in clinical trials is really actual now and requires further development form regulatory authorities, drug manufactures and investigators. This review summarizes actual international guidelines on clinical trials in geriatric population.
About the Author
I. P. MalayaRussian Federation
Malaya Irina P., MD, PhD, Senior Reseacher, Laboratory of Trans-lational Research in Gerontology.
Moscow
References
1. World Population Prospects — Population Division — United Nations. Population.un.org. https://population.un.org/wpp/Graphs/Probabilistic/PopPerc/60plus/900. Published 2020. Accessed October 20, 2020
2. Milton J.C., Hill-Smith I., Jackson S.H. Prescrib ing for older people. BMJ. 2008;336(7644):606-609. doi:10.1136/bmj.39503.424653.80
3. Ушкалова Е.А., Ткачева О.Н., Рунихина Н.К., Чухарева Н.А., Бевз А.Ю. Особенности фармакотерапии у пожилых пациентов. Введение в проблему. Рациональная Фармакотерапия в Кардиологии. 2016; 12(1): 94–100. https://doi.org/10.20996/1819-6446-2016-12-1-94-100
4. Clegg A., Young J., Iliffe S., Rikkert M.O., Rockwood K. Frailty in elderly people [published correction appears in Lancet. 2013 Oct 19; 382(9901): 1328]. Lancet. 2013; 381(9868): 752–762. DOI:10.1016/S0140-6736(12)62167-9
5. Dennis G.C. NMA's clinical trials program. J Natl Med Assoc. 1998; 90(12): 743–744
6. Cherubini A., Oristrell J., Pla X., Ruggiero C., Ferretti R., Diestre G., Clarfield A.M., Crome P., Hertogh C., Lesauskaite V., Prada G.I., Szczerbinska K., Topinkova E., Sinclair-Cohen J., Edbrooke D., Mills G.H. The persistent exclusion of older patients from ongoing clinical trials regarding heart failure. Arch Intern Med. 2011 Mar 28; 171(6): 550–556. DOI: 10.1001/archinternmed.2011.31
7. Cherubini A., Signore S., Ouslander J., Semla T., Michel J. Fighting Against Age Discrimination in Clinical Trials. J Am Geriatr Soc. 2010; 58(9): 1791-1796. DOI:10.1111/j.1532-5415.2010.03032.x
8. Greenlee R.T., Murray T., Bolden S., Wingo P.A. Cancer sta-tistics, 2000. CA Cancer J Clin. 2000 Jan-Feb; 50(1): 7–33. DOI: 10.3322/canjclin.50.1.7
9. Townsley C.A., Selby R., Siu L.L. Systematic review of bar-riers to the recruitment of older patients with cancer onto clinical trials. J Clin Oncol. 2005 May 1; 23(13): 3112–24. DOI: 10.1200/JCO.2005.00.141
10. Bugeja G., Kumar A., Banerjee A.K. Exclusion of el-derly people from clinical research: a descriptive study of pub-lished reports. BMJ. 1997; 315(7115): 1059. DOI:10.1136/bmj.315.7115.1059
11. Shenoy P., Harugeri A. Elderly patients' participa-tion in clinical trials. Perspect Clin Res. 2015; 6(4): 184–189. DOI:10.4103/2229-3485.167099
12. Unger J.M., Coltman C.A. Jr., Crowley J.J., et al. Impact of the year 2000 Medicare policy change on older patient enrollment to cancer clinical trials. J Clin Oncol. 2006; 24(1): 141–144. DOI: 10.1200/JCO.2005.02.8928
13. Cerreta F., Eichler H.G., Rasi G. Drug policy for an aging population--the European Medicines Agency's geriatric medicines strategy. N Engl J Med. 2012; 367(21): 1972–1974. DOI: 10.1056/NEJMp1209034
14. C arroll C.B., Zajicek J.P. Designing clinical trials in old-er people. Maturitas. 2011; 68(4): 337–341. DOI:10.1016/j.maturitas.2011.02.002
15. Lichtman S.M. Geriatric oncology and clinical trials. Am Soc Clin Oncol Educ Book. 2015; e127–e131. DOI: 10.14694/EdBook_AM.2015.35.e127
16. Beers E., Moerkerken D.C., Leufkens H.G., Egberts T.C., Jansen P.A. Participation of older people in preauthorization trials of recently approved medicines. J Am Geriatr Soc. 2014; 62(10): 1883–1890. DOI:10.1111/jgs.13067
17. Armstrong P.W., Zheng Y., Westerhout C.M., et al. Reduced dose tenecteplase and outcomes in elderly ST-segment eleva-tion myocardial infarction patients: Insights from the STrategic Reperfusion Early After Myocardial infarction trial [published cor-rection appears in Am Heart J. 2017 Feb;184:157]. Am Heart J. 2015; 169(6): 890–898.e1. DOI:10.1016/j.ahj.2015.03.011
18. Muzzarelli S., Brunner-La Rocca H., Pfister O., et al. Adherence to the medical regime in patients with heart failure. Eur J Heart Fail. 2010; 12(4): 389–396. DOI: 10.1093/eurjhf/hfq015
19. Denson A.C., Mahipal A. Participation of the elderly popula-tion in clinical trials: barriers and solutions. Cancer Control. 2014; 21(3): 209–214. DOI: 10.1177/107327481402100305
20. Аль-Раджави А., Зырянов С.К., Ушкалова Е.А., Бутранова О.И., Переверзев А.П. Распространённость назначений потенциально не рекомендованных лекарственных средств в практике ведения пациентов пожилого и старческого возраста. Качественная клиническая практика. 2019; (1): 65–73. https://doi.org/10.24411/2588-0519-2019-10064
21. Walsh E., Sheridan A. Factors affecting patient participation in clinical trials in Ireland: A narrative review. Contemp Clin Trials Commun. 2016; 3: 23–31. Published 2016 Mar 2. DOI:10.1016/j.conctc.2016.01.002
22. Fda.gov. https://www.fda.gov/media/71114/download. Published 2020. Accessed October 25, 2020
23. Database.ich.org. https://database.ich.org/sites/default/files/ E7_Guideline.pdf. Published 2020. Accessed October 25, 2020
24. Database.ich.org. https://database.ich.org/sites/default/files/ E7_Q%26As_Concept_Paper.pdf. Accessed October 25, 2020
25. Database.ich.org. https://database.ich.org/sites/default/files/E7_Q%26As_Q%26As.pdf. Accessed October 25, 2020
26. Database.ich.org. https://database.ich.org/sites/default/files/Q8_R2_Guideline.pdf. Published 2020. Accessed October 25, 2020
27. Jackson S.H., Jansen P.A., Mangoni А.A. Off-label prescrib-ing in older patients. Drugs Aging. 2012; 29(6): 427–434. DOI: 10.2165/11633520-000000000-00000
28. Kwint H.F., Stolk G., Faber A., Gussekloo J., Bouvy M.L. Medication adherence and knowledge of older patients with and without multidose drug dispensing. Age Ageing. 2013; 42(5): 620– 626. DOI: 10.1093/ageing/aft083
29. Stegemann S. Drug administration via enteral tubing: an unresolved but increasing challenge. Expert Opin Drug Deliv. 2015; 12(2): 159–161. DOI: 10.1517/17425247.2015.976200
30. Cornish P. «Avoid the crush»: hazards of medication admin-istration in patients with dysphagia or a feeding tube. CMAJ. 2005; 172(7): 871–872. DOI: 10.1503/cmaj.050176
31. Zedler B.K., Kakad P., Colilla S., Murrelle L., Shah N.R. Does packaging with a calendar feature improve adherence to self-ad-ministered medication for long-term use? A systematic review. Clin Ther. 2011; 33(1): 62–73. DOI: 10.1016/j.clinthera.2011.02.003
32. R ichey R.H., Craig J.V., Shah U.U., et al. The manipulation of drugs to obtain the required dose: systematic review. J Adv Nurs. 2012; 68(9): 2103–2112. DOI: 10.1111/j.1365-2648.2011.05916.x
33. .Ema.europa.eu . https://www.ema.europa.eu/en/docu-ments/scientific-guideline/reflection-paper-physical-frailty-instru-ments-baseline-characterisation-older-populations-clinical_en.pdf. Published 2020. Accessed October 25, 2020
34. Ravindrarajah R., Lee D.M., Pye S.R., et al. The ability of three different models of frailty to predict all-cause mortality: results from the European Male Aging Study (EMAS). Arch Gerontol Geriatr. 2013; 57(3): 360–368. DOI: 10.1016/j.archger.2013.06.010
35. Th eou O., Brothers T., Mitnitski A., Rockwood K. Operationalization of Frailty Using Eight Commonly Used Scales and Comparison of Their Ability to Predict All-Cause Mortality. J Am Geriatr Soc. 2013; 61(9): 1537–1551. DOI: 10.1111/jgs.12420
36. .Ema.europa.eu . https://www.ema.europa.eu/en/documents/ scientific-guideline/guideline-investigation-subgroups-confirmato-ry-clinical-trials_en.pdf. Accessed October 25, 2020
37. .Ema.europa.eu . http://www.ema.europa.eu/docs/en_GB/document_library/Other/2011/02/WC500102291.pdf. Published 2020. Accessed October 25, 2020
38. Приказ Министерства здравоохранения Российской Федерации (Минздрав России) от 21 сентября 2016 г. № 724н г. Москва «Об утверждении требований к инструкции по медицинскому применению лекарственных препаратов» http://base.garant.ru/71508082. Доступно 25 октября 2020
Review
For citations:
Malaya I.P. Clinical trials in geriatrics: actual status and international regulatory guidlines. Russian Journal of Geriatric Medicine. 2021;(1):97-104. (In Russ.) https://doi.org/10.37586/2686-8636-1-2021-97-104