Ageism in scientific research

Abstract

Ageism is one of the most prevalent and pervasive prejudices today. The exclusion of older adults from clinical studies has been identified as an element of bias and, despite having been described in the 1960s, ageism remains without a practical solution, highlighting the consolidated marginalization of this group. This review aims to provide a brief overview of the impact of this prejudice on clinical research and show potential strategies to overcome it.

Ageism; Aged; Research; Bioethics; Ethical review

Resumo

O ageísmo é um dos preconceitos mais prevalentes e pervasivos da atualidade. A exclusão de idosos de estudos clínicos tem sido identificada como elemento de viés, e, apesar de descrito já na década de 1960, o ageísmo segue sem solução prática, evidenciando a arraigada marginalização desse segmento etário. Esta revisão pretende fornecer um breve panorama da repercussão desse preconceito na pesquisa clínica e apontar possíveis estratégias para superá-lo.

Etarismo; Idoso; Pesquisa; Bioética; Revisão ética

Resumen

El ageísmo es uno de los prejuicios más prevalentes y generalizados en la actualidad. La exclusión de los ancianos de los estudios clínicos se ha identificado como un elemento de sesgo y, a pesar de que ya se describió en la década de 1960, el ageísmo sigue sin tener una solución práctica, lo que pone de manifiesto la arraigada marginación de este segmento de edad. Esta revisión pretende ofrecer una breve panorámica de las repercusiones de este prejuicio en la investigación clínica y señalar posibles estrategias para superarlo.

Ageísmo; Anciano; Investigación; Bioética; Revisión ética

The term “ageism” was proposed by Robert Butler in 1969 to describe the “prejudice by one age group toward other age groups” ⁴. It is a broad concept that was later reformulated to “attitudes of prejudice and assumptions about older people, discriminatory practices or structural elements that perpetuate stereotypes about older people” ⁵. Because of ageism and its biased and stereotyped, predominantly negative representation, the older adults are considered a homogeneous group, characterized by weakness, illness, and senility ⁶.

As a result, they are rejected and disrespected, their individuality is devalued and they are considered unworthy of the rights and privileges granted to other members of society ⁷. Therefore, this population has been excluded from social participation in various everyday scenarios. In clinical research, older adults remain underrepresented, either because of arbitrary or omitted age limitations, or because of a concern with clinical frailty as a determinant of inadequacy.

This review aims to describe the practice of ageism in scientific research, analyze its impact on the older population and the rest of society, and highlight challenges to better understanding and eliminating it.

Particularities of ageism in clinical research

The ethical principles for medical research involving human subjects comply with the Declaration of Helsinki, adopted at the 18th General Assembly of the World Medical Association in Finland in June 1964. According to Article 13 of the Declaration, groups that are underrepresented in medical research should be provided appropriate access to participation in research ⁸.

Therefore, ethical supervision of clinical research is justified, as it regulates the requirements and best practices in this activity. In this sense, subsequent codes of research ethics were created, such as the Belmont Report ⁹ of 1979, which highlights the best practices in the selection of research subjects.

Research is regulated and operationalized by institutional committees, and evaluated according to specific criteria for approval, according to fundamental ethical elements – fairness, respect for persons, and beneficence. Among these rules, it should be noted that the selection of research subjects must be equitable, respecting the principle of fairness ¹⁰.

The underrepresentation of the older population in research has been observed since the 1990s, highlighting the need to pay attention to this problem and its solution ³. Following a document issued in 1989 by the Food and Drug Administration encouraging research on drug safety in older adults and highlighting the lack of data in the literature ¹¹, the International Conference on Harmonization ¹² was organized to determine the pharmacokinetic and pharmacodynamic characteristics of drugs used predominantly by geriatric patients, which were unknown at the time.

This initiative aimed to consolidate knowledge about drugs used in diseases that are more prevalent in this population (such as Alzheimer’s disease) or intrinsically related to them (comorbidities, organ failure). Finally, the guideline ¹² recommended that the exclusions of new drug formulations or drug combinations, determined by the technical evaluations performed by this task force after taking into account physiological particularities and the most prevalent conditions among older adults (such as organ failure), should be recorded and reported to the authorities, based on objective criteria (estimates of disease prevalence by age or the age distribution of other drugs of the same class or used for the same indication) ¹².

Although emblematic for being a pioneering initiative, it failed when it stated that clinically important differences would normally be detected in a group of 100 patients over 65 years of age ¹². Unfortunately, the standard population sample of 100 people over 65 years of age was then adopted, as it was considered sufficient to rule out age-related clinical peculiarities, without evidence that it was appropriate, perhaps only as a minimum threshold ³.

Many studies have raised concerns about this issue, such as an Australian study which showed that most (85%) national pharmacotherapy guidelines referred to the elderly, but omitted any reference to age ¹³. In addition, a systematic review of 4,341 randomized clinical trials ¹⁴ revealed an alarming finding: most studies did not include explicit minimum or maximum age limits, or when they did, no explanation of the reason for such limits was provided.

Of note, the omission of such information from the inclusion criteria may often imply a recruitment bias, favoring younger participants ¹⁵. Finally, even considering the associated non-intentionality and involuntariness, the devaluation of this age group is evident, perhaps based on limited stereotypes. Anyway, this situation is inappropriate for a research environment and, even hidden, it constitutes ageism ¹⁶.

This problem is even worse in less developed countries, where ageism is more prevalent, healthy life expectancy is lower, and the likelihood of illness among older adults is higher. In these countries, the increased exposure of the population to health problems in old age reinforces negative attitudes towards aging ¹⁷.

According to Shenoy and Harugeri ¹⁸, the regulatory authorities in these countries have several concerns about enrolling elderly patients (aged 65 and older) in clinical trials:

• lower life expectancy when compared to the Western population;

• greater dependence on health care by this population, which is seen as a barrier to participate in clinical trials;

• not exposing vulnerable populations to experimental drugs;

• comorbidities that may affect efficacy and safety outcomes; and

• potential increase in serious adverse events, especially death.

Therefore, scientific progress in the geriatric population presents a true ethical dilemma. While it requires the participation of older adults to ensure representativeness, it must recruit competent individuals to give valid consent (a fundamental requirement in research ethics) ¹⁹. In other words, research on older people is both ethically necessary and ethically suspect ¹⁹.

Discussion

Ageing is a controversial subject, neglected in many ways. The definition of age shows that, regardless of the cut-off point used, the terms “older,” “old age,” and “elderly” cover people with an age difference of up to 35 years ²⁰.

The incorporation of ageist practices into scientific research was first described by Butler ⁵, who designed structural or institutionalized stereotypes that result in practices and policies that harm older people. Often inseparable from other types of prejudice, ageism can be expressed in organizational and academic environments. In these environments, known for the pressure to be productive and achieve goals, it can be seen both against researchers ²¹ and, eventually, against individuals to be recruited.

Despite being the major consumers of new therapies, older people have been underrepresented in the clinical trials that led to the discovery of these drugs ¹,¹⁴. As a result, applying research to target populations is a challenging task ¹⁴, that is, there is insufficient evidence and knowledge about the responses of geriatric patients to drugs ¹⁸. This is because medical research involving young and middle-aged people does not necessarily benefit the elderly ²², requiring the representative participation of this population.

Some strategies to mitigate the harmful effects of ageism in clinical research are: the adoption of inclusive public policies, the establishment of targeted guidelines, and raising awareness among the scientific community ¹.

With a view to inclusion, a strategy has been proposed for advising researchers based on five elements, called 5Ts (target population, team, tools, time, tips to accommodate) ²³. This strategy emphasizes:

• representation of the target population in order to avoid exclusions that limit the generalizability of the study;

• the importance of creating research teams with experience in aging, including geriatric researchers and aging specialists;

• appropriate tools to measure function and outcomes reported by the patient;

• allowing time for extended study visits, with access to food and medication; and

• meeting common needs with practical tips, such as provision for transportation and adequate printed material.

Challenges related to the recruitment phases and research settings seem equally relevant. The former concerns diverse and fair participation, respecting the representativeness of the sample, while the latter highlights special situations such as home confinement or palliative care ²². Cognitive limitation also raises several ethical issues, making older people particularly vulnerable to exclusion.

Understanding informed consent and agreeing with it requires perception, memory, judgment and reasoning skills, correlated with educational level and time availability ²²,²⁴. For this reason, researchers must be trained to communicate research results to the target audience in a comprehensible way, as these data are considered difficult for older people to understand ²⁵. Solutions must be anticipated and incorporated into research projects.

The British Geriatrics Society has implemented initiatives to change geriatric health policies, procedures, and behaviors, although unfortunately it has not yet achieved concrete changes ²⁶. The American Geriatrics Society recognizes age disparities and prejudices in North American health policies and is committed to promoting fairness and eliminating these barriers ²⁷.

In Brazil, age issues have been on the government policy agenda for the past two decades, driven by the need to reform social security ²⁸. Then, legal provisions, such as the Statute of the Elderly ²⁹, are examples of the recognition of these challenges by legislators and government officials ²⁸.

Since current practices are exclusionary, there are challenges to be overcome, and it is essential to implement policies that promote communication and the preparation of researchers and health professionals in order to bring the issue to the attention of those responsible for scientific production. It is the responsibility of the researcher to protect the rights and well-being of research participants and ensure that research is conducted in accordance with appropriate ethical standards.

Final considerations

The engagement of the community and governmental institutions that ensure compliance with the regulations contained in national health policies must be the driving force to change dogmatic scientific precepts that prevent the equitable participation of age groups under fictitious claims. In addition, the engagement of research organizations and research awareness are required, driven by the search for truth and dissatisfaction with the status quo. Inclusive strategies would reduce the current imbalance that excludes the older people from their fair and essential participation in scientific studies.

Fighting against ageism in clinical research is not just a matter of practicing empathy or intergenerational alterity. It means ensuring respect for the individuality and rights of older people, with diversity as a social value and ethics as a humanitarian principle. It also fulfills the social role of fairness and equity that enables the exercise of citizenship.

References

• ¹ Petrovsky DV, Ðoàn LN, Loizos M, O'Conor R, Prochaska M, Tsang M et al. Key recommendations from the 2021 "inclusion of older adults in clinical research" workshop. J Clin Transl Sci [Internet]. 2022 [acesso 18 out 23];6(1):e55. DOI: 10.1017/cts.2022.1
  » https://doi.org/10.1017/cts.2022.1
• ² Barnett K, Mercer SW, Norbury M, Watt G, Wyke S, Guthrie B. Epidemiology of multimorbidity and implications for health care, research, and medical education: a cross-sectional study. Lancet [Internet]. 2012 [acesso 19 out 23];380(9836):37-43. DOI: 10.1016/S0140-6736(12)60240-2
  » https://doi.org/10.1016/S0140-6736(12)60240-2
• ³ Crome P, Cherubini A, Oristrell J. The PREDICT (increasing the participation of the elderly in clinical trials) study: the charter and beyond. Expert Rev Clin Pharmacol [Internet]. 2014 [acesso 26 nov 23];7(4):457-68. DOI: 10.1586/17512433.2014.922864
  » https://doi.org/10.1586/17512433.2014.922864
• ⁴ Butler RN. Age-ism: another form of bigotry. Gerontologist [Internet]. 1969 [acesso 23 out 23];9(4):243-6. DOI: 10.1093/geront/9.4_Part_1.243
  » https://doi.org/10.1093/geront/9.4_Part_1.243
• ⁵ Butler RN. Ageism: a foreword. J Soc Issues [Internet]. 1980 [acesso 23 out 23];36:8-11. p. 8. Tradução livre. DOI: 10.1111/j.1540-4560.1980.tb02018.x
  » https://doi.org/10.1111/j.1540-4560.1980.tb02018.x
• ⁶ Sargent-Cox K. Ageism: we are our own worst enemy. Int Psychogeriatr [Internet]. 2017 [acesso 23 out 23];29(1):1-8. DOI: 10.1017/S1041610216001939
  » https://doi.org/10.1017/S1041610216001939
• ⁷ Allen JO, Solway E, Kirch M, Singer D, Kullgren JT, Malani PN. The everyday ageism scale: development and evaluation. J Aging Health [Internet]. 2022 [acesso 23 nov 23];34(2):147-57. DOI: 10.1177/08982643211036131
  » https://doi.org/10.1177/08982643211036131
• ⁸ World Medical Association. Declaration of Helsinki: ethical principles for medical research involving human subjects. WMA [Internet]. 2013 [acesso 27 nov 23]. Tradução livre. Disponível: https://tny.im/qMU5l
  » https://tny.im/qMU5l
• ⁹ The Belmont Report: Ethical guidelines for the protection of human subjects. U.S. Department of Health & Human Services [Internet]. 1978 [acesso 27 nov 23]. Disponível: https://tny.im/rAiGX
  » https://tny.im/rAiGX
• ¹⁰ McNair L. Ethical and regulatory oversight of clinical research: the role of the Institutional Review Board. Exp Biol Med (Maywood) [Internet]. 2022 [acesso 27 nov 23];247(7):561-6. DOI: 10.1177/15353702221078216
  » https://doi.org/10.1177/15353702221078216
• ¹¹ Food and Drug Administration. Guideline for the study of drugs likely to be used in the elderly [Internet]. Rockville: Food and Drug Administration; 1989 [acesso 26 nov 2023]. Disponível: https://tny.im/311Cl
  » https://tny.im/311Cl
• ¹² European Medicines Agency. ICH E7 studies in support of special populations: geriatrics. European Medicines Agency [Internet]. 1994 [acesso 26 nov 23]. Disponível: https://tny.im/3YXNV
  » https://tny.im/3YXNV
• ¹³ Singh S, Bajorek B. Defining "elderly" in clinical practice guidelines for pharmacotherapy. Pharm Pract (Granada) [Internet]. 2014 [acesso 15 nov 23];12(4):489. DOI: 10.4321/s1886-36552014000400007
  » https://doi.org/10.4321/s1886-36552014000400007
• ¹⁴ Thake M, Lowry A. A systematic review of trends in the selective exclusion of older participant from randomised clinical trials. Arch Gerontol Geriatr [Internet]. 2017 [acesso 26 nov 23];72:99-102. DOI: 10.1016/j.archger.2017.05.017
  » https://doi.org/10.1016/j.archger.2017.05.017
• ¹⁵ 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 [Internet]. 2011 [acesso 24 nov 23];26(7):783-90. DOI: 10.1007/s11606-010-1629-x
  » https://doi.org/10.1007/s11606-010-1629-x
• ¹⁶ Allen JO, Solway E, Kirch M, Singer D, Kullgren JT, Moïse V, Malani PN. Experiences of everyday ageism and the health of older US adults. JAMA Netw Open [Internet]. 2022 [acesso 23 nov 23];5(6):e2217240. DOI: 10.1001/jamanetworkopen.2022.17240
  » https://doi.org/10.1001/jamanetworkopen.2022.17240
• ¹⁷ Officer A, Thiyagarajan JA, Schneiders ML, Nash P, Fuente-Núñez V. Ageism, healthy life expectancy and population ageing: how are they related? Int J Environ Res Public Health [Internet]. 2020 [acesso 30 nov 23];17(9):3159. DOI: 10.3390/ijerph17093159
  » https://doi.org/10.3390/ijerph17093159
• ¹⁸ Shenoy P, Harugeri A. Elderly patients' participation in clinical trials. Perspect Clin Res [Internet]. 2015 [acesso 28 nov 23];6(4):184-9. DOI: 10.4103/2229-3485.167099
  » https://doi.org/10.4103/2229-3485.167099
• ¹⁹ Schafer A. Research on elderly subjects. In: Weisstub DN, Thomasma DC, Gauthier S, Tomossy GF, editores. Aging: decisions at the end of life [Internet]. Dordrecht: Springer; 2001 [acesso 1º dez 23]. p. 171-205. (International Library of Ethics, Law, and the New Medicine; vol. 12). DOI: 10.1007/978-94-015-9682-4_10
  » https://doi.org/10.1007/978-94-015-9682-4_10
• ²⁰ Markham S. Professional ageism: the impact of ageism among research and healthcare professionals on older patients: a systematic review; The impact of ageism among legal and financial professionals on older people: systematised reviews [dissertação] [Internet]. Kensington: University of New South Wales; 2021 [acesso 18 out 23]. DOI: 10.26190/unsworks/22423
  » https://doi.org/10.26190/unsworks/22423
• ²¹ Viana LO, Helal DH. Ageísmo na carreira acadêmica: um estudo com professores universitários. Educação & Realidade [Internet]. 2023 [acesso 25 out 23];48:e121896. DOI: 10.1590/2175-6236121896vs02
  » https://doi.org/10.1590/2175-6236121896vs02
• ²² Ilgili O, Arda B, Munir K. Ethics in geriatric medicine research. Turk Geriatri Derg [Internet]. 2014 [acesso 27 nov 23];17(2):188-95. Disponível: https://pubmed.ncbi.nlm.nih.gov/25489272
  » https://pubmed.ncbi.nlm.nih.gov/25489272
• ²³ Bowling CB, Whitson HE, Johnson II TM. The 5Ts: preliminary development of a framework to support inclusion of older adults in research. J Am Geriatr Soc [Internet]. 2019 [acesso 25 nov 23];67(2):342-6. DOI: 10.1111/jgs.15785
  » https://doi.org/10.1111/jgs.15785
• ²⁴ López-Parra M, Zamora-Carmona F, Sianes-Gallén M, López-González E, Gil-Rey D, Costa-Ventura H et al. Patient information and informed consent for research in the elderly: lessons learned from a randomized controlled trial. Healthcare (Basel) [Internet]. 2022 [acesso 27 nov 23];10(6):1036. DOI: 10.3390/healthcare10061036
  » https://doi.org/10.3390/healthcare10061036
• ²⁵ Haak M, Ivanof S, Barenfeld E, Berge I, Lood Q. Research as an essentiality beyond one’s own competence: an interview study on frail older people’s view of research. Res Involv Engagem [Internet]. 2021 [acesso 28 nov 23];7(1):91. DOI: 10.1186/s40900-021-00333-7
  » https://doi.org/10.1186/s40900-021-00333-7
• ²⁶ Street A, Maynou L, Conroy S. Did the Acute Frailty Network improve outcomes for older people living with frailty? A staggered difference-in-difference panel event study. BMJ Qual Saf [Internet]. 2023 [acesso 23 nov 23];32(12):721-31. DOI: 10.1136/BMJQS-2022-015832
  » https://doi.org/10.1136/BMJQS-2022-015832
• ²⁷ Farrell TW, Hung WW, Unroe KT, Brown TR, Furman CD, Jih J et al. Exploring the intersection of structural racism and ageism in healthcare. J Am Geriatr Soc [Internet]. 2022 [acesso 30 nov 23];70(12):3366-77. DOI: 10.1111/jgs.18105
  » https://doi.org/10.1111/jgs.18105
• ²⁸ Goldani AM. "Ageism" in Brazil: what is it? Who does it? What to do with it? Rev Bras Estud Popul [Internet]. 2010 [acesso 1º dez 23];27(2):385-405. DOI: 10.1590/S0102-30982010000200009
  » https://doi.org/10.1590/S0102-30982010000200009
• ²⁹ Brasil. Lei nº 10.741, de 1º de outubro de 2003. Dispõe sobre o Estatuto da Pessoa Idosa e dá outras providências. Diário Oficial da União [Internet]. Brasília, 3 out 2003 [acesso 18 out 23]. Disponível: https://tny.im/6cyka
  » https://tny.im/6cyka

Publication Dates

• Publication in this collection
  13 Dec 2024
• Date of issue
  2024

History

• Received
  12 Dec 2023
• Reviewed
  20 May 2024
• Accepted
  13 June 2024