Drugs & Aging

, Volume 20, Issue 15, pp 1087–1097 | Cite as

The Doctor’s Duty to the Elderly Patient in Clinical Trials

  • Antony BayerEmail author
  • Mark Fish
Current Opinion


The ethical principles of beneficence (or non-maleficence), respect for persons and justice apply to both good medical practice and clinical research. Doctors have a duty to offer to their patients, of all ages, the opportunity to take part in clinical trials and to ensure that research is appropriately designed and conducted.

Barriers to participation of elderly patients in clinical trials include complex protocols with onerous outcome measures, a research focus on aggressive therapies with substantial toxicity, restrictive entry criteria unnecessarily excluding concurrent conditions and medication, patients’ and families’ limited expectations of benefits and lack of financial, logistic and social support.

Participation is encouraged when attitudes of care staff towards research are positive, altruistic motives are acknowledged, approval of family members is gained and protocols are designed for patient rather than staff convenience. Special consideration should be given to ensuring that patient consent is fully informed and freely given.

Elderly patients may have more difficulty comprehending consent information and particular attention should be given to compensating for communication and sensory deficits, improving readability of information sheets and consent forms, and considering the use of innovative consent procedures. Those with cognitive impairment and the institutionalised are vulnerable to exploitation and require special consideration and management.


Elderly People Trial Participation Altruistic Motive Elderly Cancer Patient Good Medical Practice 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



Antony Bayer has been paid by pharmaceutical companies to conduct clinical trials of medications in elderly patients. Mark Fish is part funded by the Alzheimer’s Society of the United Kingdom. No sources of funding were used in the preparation of this manuscript.


  1. 1.
    Department of Health. National Service Framework for Older People. London: Department of Health, 2001. Available from URL: [Accessed 2003 Sep 4]Google Scholar
  2. 2.
    Department of Health. Statistical Bulletin 1999/17: statistics of prescriptions dispensed in the community: 1988–1998. London: Department of Health, 1999Google Scholar
  3. 3.
    Hammerlein A, Derendorf H, Lowenthal DT. Pharmacokinetic and pharmacodynamic changes in the elderly: clinical implications. Clin Pharmacokinet 1998; 35: 49–64PubMedCrossRefGoogle Scholar
  4. 4.
    Atkin PA, Veitch PC, Veitch EM, et al. The epidemiology of serious adverse drug reactions among the elderly. Drugs Aging 1999; 14: 141–52PubMedCrossRefGoogle Scholar
  5. 5.
    Food and Drug Administration, Department of Health and Human Services (USA). International Conference on Harmonisation; guideline on studies in support of special populations: geriatrics: availability. Fed Regist 1994; 59: 33398–400Google Scholar
  6. 6.
    National Commission for then protection of Human Subjects of Biomedical and Behavioural Research. The Belmont Report: ethical principles and guidelines for the protection of human subjects of research. Washington, DC: US Government Printing Office, 1979Google Scholar
  7. 7.
    Fleischman AR. Developing regulations for research involving adults who lack decision making capacity. Trans Am Clin Climatol Assoc 1999, 110: 131–45PubMedGoogle Scholar
  8. 8.
    General Medical Council. Research: the role and responsibilities of doctors. London: General Medical Council, 2002. Available from URL: [Accessed 2003 Sep 4]Google Scholar
  9. 9.
    Nuremberg Code. Permissible medical experiments, trials of war criminals before the Nuremberg military tribunals under Control Council Law No.10: Nuremberg October 1946–April 1949, Vol 2. Washington, DC: US Government Printing Office, 1946: 181–2Google Scholar
  10. 10.
    World Medical Association. Declaration of Helsinki: ethical principles for medical research involving human subjects. Ferney-Voltaire: World Medical Association, 2000. Available from URL: [Accessed 2003 Sep 4]
  11. 11.
    National Bioethics Advisory Commission. Ethical and policy issues in research involving human participants. Vol. 1. Rockville (MD): National Bioethics Advisory Commission, 2000. Available from URL: [Accessed 2003 Sep 4]Google Scholar
  12. 12.
    American Geriatrics Society Ethics and Research Committees. The responsible conduct of research. J Am Geriatr Soc 2001; 49: 1120–2CrossRefGoogle Scholar
  13. 13.
    Bugeja G, Kumar A, Banerjee AK. Exclusion of elderly people from clinical research: a descriptive study of published reports. BMJ 1997; 315: 1059PubMedCrossRefGoogle Scholar
  14. 14.
    Bayer A, Tadd W. Unjustified exclusion of elderly people from studies submitted to research ethics committee for approval: descriptive study. BMJ 2000; 321: 992–3PubMedCrossRefGoogle Scholar
  15. 15.
    Rogers SL, Farlow MR, Doody SR, et al. A 24 week, double blind placebo controlled trial of donepezil in patients with AD. Neurology 1998; 50: 136–45PubMedCrossRefGoogle Scholar
  16. 16.
    Rosier M, Anand R, Cicin-Sian A, et al. Efficacy and safety of rivastigmine in patients with Alzheimer’s disease: international randomised controlled trial. BMJ 1999; 318: 633–58Google Scholar
  17. 17.
    Weisstub DN, Florez-Arboleda J, Tomossy GF. Establishing the boundaries of ethically permissible research with special populations. Health Law Can 1996; 17: 45–63PubMedGoogle Scholar
  18. 18.
    Koops L, Lindley RI. Thrombolysis for acute ischaemic stroke: consumer involvement in design of new randomised controlled trial. BMJ 2002; 325: 415–7PubMedCrossRefGoogle Scholar
  19. 19.
    Yastrubetskaya O, Chiu E, O’Connell S. Is good clinical research practice for clinical trials good clinical practice? Int J Geriatr Psychiatry 1997; 12: 227–31PubMedCrossRefGoogle Scholar
  20. 20.
    Yusuf S, Held P, Teo KK, et al. Selection of patients for randomised controlled trials: implications of wide or narrow eligibility criteria. Stat Med 1990; 9: 73–86PubMedCrossRefGoogle Scholar
  21. 21.
    Britton A, McKee M, Black N, et al. Threats to applicability of randomised trials: exclusions and selective participation. J Health Serv Res Policy 1999; 4: 112–21PubMedGoogle Scholar
  22. 22.
    Bene J, Liston R. The special problems of conducting clinical trials in elderly patients. Rev Clin Gerontol 1997; 7: 1–3CrossRefGoogle Scholar
  23. 23.
    Hutchins LF, Unger JM, Crowley JJ, et al. Under-representation of patients 65 years of age or older in cancer-treatment trials. N Engl J Med 1999; 341: 2061–7PubMedCrossRefGoogle Scholar
  24. 24.
    Kemeny M, Muss HB, Kornblith AB, et al. Barriers to participation of older women with breast cancer in clinical trials. Proc Am Soc Clin Oncol 2000; 19: 602aGoogle Scholar
  25. 25.
    Lee PY, Alexander KP, Hammill BG, et al. Representation of elderly persons and women in published randomized trials of acute coronary syndromes. JAMA 2001; 286: 708–13PubMedCrossRefGoogle Scholar
  26. 26.
    Mitchell SL, Sullivan EA, Lipsitz LA. Exclusion of elderly subjects from clinical trials for Parkinson’s disease. Arch Intern Med 1997; 157: 1393–8CrossRefGoogle Scholar
  27. 27.
    Bandyopadhyay S, Bayer AJ, O’Mahoney MS. Age and gender bias in statin trials. QJM 2001; 94: 127–32PubMedCrossRefGoogle Scholar
  28. 28.
    Trimble EL, Carter CL, Cain D, et al. Representation of older patients in cancer treatment trials. Cancer 1994, 14Google Scholar
  29. 29.
    Department of Health and Human Services. Medicare coverage issues manual transmittal 126. Washington, DC: US Department of Health and Human Services, 2000. Available from URL: [Accessed 2003 Sep 4]Google Scholar
  30. 30.
    Monfardini S, Sorio R, Boes GH, et al. Entry and evaluation of elderly patients in European Organisation for research and treatment of Cancer (EORTC) new drug development studies. Cancer 1995; 76: 333–6PubMedCrossRefGoogle Scholar
  31. 31.
    The Collaborative Ocular Melanoma Study Group. Sociodemographic and clinical predictors of participation in two randomized trials: findings from the Collaborative Ocular Melanoma Study COMS Report No. 7. Control Clin Trials 2001; 22: 526–37CrossRefGoogle Scholar
  32. 32.
    Kaye JM, Lawton P, Kaye D. Attitudes of elderly people about clinical research on aging. Gerontologist 1990; 30: 100–6PubMedCrossRefGoogle Scholar
  33. 33.
    Maine LL, Rodriguez R, Brown J. Geriatric drug testing: who will volunteer?: a descriptive survey. J Geriatr Drug Ther 1988; 2: 63–77CrossRefGoogle Scholar
  34. 34.
    Ameer B, Burlingame MB. Difficulties enrolling elderly patients in pharmacokinetic studies. J Geriatr Drug Therapy 1990; 4: 61–7Google Scholar
  35. 35.
    Cohen-Mansfield J, Kerin P, Pawlson G, et al. Informed consent for research in a nursing home: processes and issues. Gerontologist 1988; 28: 355–9PubMedCrossRefGoogle Scholar
  36. 36.
    Sachs GA, Stocking CB, Stern R, et al. Ethical aspects of dementia research: informed consent and proxy consent. Clin Res 1994; 42: 403–12PubMedGoogle Scholar
  37. 37.
    Stanley B, Guido J, Stanley M, et al. The elderly patient and informed consent:empiricalfindings. JAMA 1984; 252: 1302–6PubMedCrossRefGoogle Scholar
  38. 38.
    Sugarman J, McCrory DC, Hubal RC. Getting meaningful informed consent from older adults: a structured literature review of empirical research. J Am Geriatr Soc 1998; 46: 517–24PubMedGoogle Scholar
  39. 39.
    Adams J, Silverman M, Musa D, et al. Recruiting older adults for clinical trials. Control Clin Trials 1997; 18: 14–26PubMedCrossRefGoogle Scholar
  40. 40.
    Erlen JA, Sauder RJ, Mellors MP. Incentives in research: ethical issues. Orthop Nurs 1999; 18: 84–7PubMedGoogle Scholar
  41. 41.
    Cherniack EP. Informed consent for medical research by the elderly. Exp Aging Res 2002; 28: 183–98PubMedCrossRefGoogle Scholar
  42. 42.
    Applebaum PS, Grisso T. Assessing patient’s capacities to consent to treatment. N Engl J Med 1988; 319: 1635–8CrossRefGoogle Scholar
  43. 43.
    High DM, Doole MM. Ethical and legal issues in conducting research involving elderly subjects. Behav Sci Law 1995; 13: 319–35PubMedCrossRefGoogle Scholar
  44. 44.
    Alexander M. Clinical determination of mental competence: a theory and a retrospective study. Arch Neurol 1988; 45: 23–6PubMedCrossRefGoogle Scholar
  45. 45.
    Schindler B, Rachmandi D, Matthews M, et al. Competency and the frontal lobe: the impact of executive dysfunction on decisional capacity. Psychosomatics 1995; 36: 400–4PubMedCrossRefGoogle Scholar
  46. 46.
    Marson D, Harreil L. Executive dysfunction and loss of capacity to consent to medical treatment in patients with Alzheimer’s disease. Semin Clin Neuropsychiatry 1999; 4: 41–9PubMedGoogle Scholar
  47. 47.
    Dymek MP, Atchison P, Harrell L, et al. Competency to consent to medical treatment in cognitively impaired patients with Parkinson’s disease. Neurology 2001; 56: 17–24PubMedCrossRefGoogle Scholar
  48. 48.
    CIOMS/WHO International ethical guidelines for biomedical research involving human subjects. Geneva: Council for International Organisations of Medical Societies/World Health Organisation, 2002Google Scholar
  49. 49.
    Spiro HM. Constraint and consent: on being a patient and a subject. N Engl J Med 1975; 293: 1134–5PubMedCrossRefGoogle Scholar
  50. 50.
    Cassel CK. Research in nursing homes: ethical issues. J Am Geriatr Soc 1985; 33: 795–9PubMedGoogle Scholar
  51. 51.
    Sachs GA, Rhymes J, Cassel CK. Biomedical and behavioural research in nursing homes: guidelines for ethical investigations. J Am Geriatr Soc 1993; 41: 771–7PubMedGoogle Scholar
  52. 52.
    Marson DC, Ingram KK, Cody HA, et al. Assessing the competency of patients with Alzheimer’s disease under different legal standards. Arch Neurol 1995; 52: 949–54PubMedCrossRefGoogle Scholar
  53. 53.
    Pucci E, Belardinelli N, Borsetti G, et al. Information and competency for consent to pharmacological clinical trials in Alzheimer disease: an empirical analysis in patients and family caregivers. Alzheimer Dis Assoc Disord 2001; 15: 146–54PubMedCrossRefGoogle Scholar
  54. 54.
    CERES. Medical research and you. London: Consumers for Ethics in Research (CERES), 2001Google Scholar
  55. 55.
    Cassileth BR, Zupkis RV, Sutton-Smith K, et al. Informed consent: why are its goals imperfectly realised? N Engl J Med 1980; 302: 896–900PubMedCrossRefGoogle Scholar
  56. 56.
    Featherstone K, Donovan JL. Random allocation or allocation at random?: patient perceptions in a randomised controlled trial. BMJ 1998; 317: 1177–80PubMedCrossRefGoogle Scholar
  57. 57.
    Riecken HW, Ravich R. Informed consent to biomedical research in veterans administration hospitals. JAMA 1982; 248: 344–8PubMedCrossRefGoogle Scholar
  58. 58.
    Taub HA. Informed consent, memory and age. Gerontologist 1980; 20: 686–90PubMedCrossRefGoogle Scholar
  59. 59.
    Taub HA, Baker MT, Sturr JF. Informed consent for research: effects of readability, patient age, and education. J Am Geriatr Soc 1986; 34: 601–6PubMedGoogle Scholar
  60. 60.
    Howard JM, DeMets D, the BHAT Research Group. How informed is informed consent?. The BHAT experience. Control Clin Trials 1981; 2: 287–303PubMedCrossRefGoogle Scholar
  61. 61.
    LoVerde ME, Prochazka AV, Byyny RL. Research consent forms: continued unreadability and increasing length. J Gen Intern Med 1989; 4: 410–2PubMedCrossRefGoogle Scholar
  62. 62.
    Grossman SA, Piantadosi S, Covahey C. Are informed consent forms that describe clinical oncology research protocols readable by most patients and their families? J Clin Oncol 1994; 12: 2211–5PubMedGoogle Scholar
  63. 63.
    Ratzan RM. Communication and informed consent in clinical geriatrics. Int J Aging Hum Dev 1986; 23: 17–26PubMedCrossRefGoogle Scholar
  64. 64.
    Royall DR, Cordes J, Polk M. Executive control and the comprehension of medical information by elderly retirees. Exp Aging Res 1997; 23: 301–13PubMedCrossRefGoogle Scholar
  65. 65.
    Schaeffer MH, Krante DS, Wichmann A, et al. The impact of disease severity on the informed consent process in clinical research. Am J Med 1996; 100: 261–8PubMedCrossRefGoogle Scholar
  66. 66.
    Bjorn E, Rossel P, Holm S. Can the written information to research subjects be improved?: an empirical study. J Med Ethics 1999; 25: 263–7PubMedCrossRefGoogle Scholar
  67. 67.
    Raich PC, Plomer KD, Coyne CA. Literacy, comprehension and informed consent in clinical research. Cancer Invest 2001; 19: 437–45PubMedCrossRefGoogle Scholar
  68. 68.
    Philipson SJ, Doyle MA, Nightingale C, et al. Effectiveness of a writing improvement intervention program on the readability of the research informed consent document. J Invest Med 1999; 47: 468–76Google Scholar
  69. 69.
    Taub HA, Baker MT, Kline GE, et al. Comprehension of informed consent by young-old through old-old volunteers. Exp Aging Res 1987; 13: 173–8PubMedCrossRefGoogle Scholar
  70. 70.
    Tymchuk AJ, Ouslander JG, Rahbar B, et al. Medical decisionmaking among elderly people in long-term care. Gerontologist 1988; 28: 59–63PubMedCrossRefGoogle Scholar
  71. 71.
    Tymchuk AJ, Ouslander JG, Rader N. Informing the elderly: a comparison of four methods. J Am Geriatr Soc 1986; 24: 818–22Google Scholar
  72. 72.
    Taub HA, Baker MT. Effect of repeated testing upon comprehension of informed consent materials by elderly volunteers. Exp Aging Res 1983; 9: 135–8PubMedCrossRefGoogle Scholar
  73. 73.
    Grisso T, Appelbaum P. Mentally ill and non-mentally ill patients’ abilities to understand informed consent disclosures for medication: preliminary data. Law Hum Behav 1991; 15: 377–88PubMedCrossRefGoogle Scholar
  74. 74.
    Olde Rikkert MGM, van der Beckan JHK, ten Have MAMJ, et al. Experienced consent in geriatrics research: a new method to optimize the capacity to consent in frail elderly subjects. J Med Ethics 1997; 23: 271–6CrossRefGoogle Scholar
  75. 75.
    Aaronson NK, Visser-Pol E, Leenhouts GH, et al. Telephone-based nursing intervention improves the effectiveness of the informed consent process in cancer clinical trials. J Clin Oncol 1996; 14: 984–96PubMedGoogle Scholar
  76. 76.
    Christensen K, Haroun A, Schneiderman L, et al. Decision making capacity for informed consent in the older population. Bull Am Acad Psychiatry Law 1995; 23: 353–65PubMedGoogle Scholar
  77. 77.
    Hayley DC, Cassel CK, Snyder L, et al. Ethical and legal issues in nursing home care. Arch Intern Med 1996; 156: 249–56PubMedCrossRefGoogle Scholar
  78. 78.
    Bonnie LLB. Research with cognitively impaired subjects: unfinished business in the regulation of human research. Arch Gen Psychiatry 1997; 54: 105–11PubMedCrossRefGoogle Scholar
  79. 79.
    Brodaty H, Dresser R, Eisner M, et al. Consensus statement: Alzheimer’s disease international and international working group for harmonization of dementia drug guidelines for research involving human subjects with dementia. Alzheimer Dis Assoc Disord 1999; 13: 71–9PubMedCrossRefGoogle Scholar
  80. 80.
    Holzer JC, Gansler DA, Moczynski NP, et al. Cognitive functions in the informed consent examination process: a pilot study. J Am Acad Psychiatry Law 1997; 25: 531–40PubMedGoogle Scholar
  81. 81.
    Marson DC, Cody HA, Ingram KK, et al. Neuropsychological predictors of competency in AD using a rational reasons legal standard. Arch Neurol 1995; 52: 955–9PubMedCrossRefGoogle Scholar
  82. 82.
    Janofsky JS, McCarthy RJ, Folstein MF. The Hopkins competency assessment test: a brief method for evaluating patients’ capacity to give informed consent. Hosp Community Psychiatry 1992; 43: 132–6PubMedGoogle Scholar
  83. 83.
    Grisso T, Appelbaum PS, Hill-Fotouhi C. The MacCAT-T: a clinical tool to assess patients’ capacities to make treatment decisions. Psychiatr Serv 1997; 48: 1415–9PubMedGoogle Scholar
  84. 84.
    Marson DC, Earnst KS, Jamil F, et al. Consistency of physicians’ legal standards and personal judgements of competency in patients with Alzheimer’s disease. J Am Geriatr Soc 2000; 48: 911–8PubMedGoogle Scholar
  85. 85.
    Singer EA, Mullner M. Implications of the EU directive on clinical trials for emergency medicine. BMJ 2002; 324: 1169–70PubMedCrossRefGoogle Scholar
  86. 86.
    Wichman A, Sandler AL. Research involving critically ill subjects in emergency circumstances: new regulations, new challenges. Neurology 1997; 48: 1151–7PubMedCrossRefGoogle Scholar
  87. 87.
    White S, Barua P, O’Mahony MS, et al. Research in older patients: consent and assent. Age Ageing 2002; 31Suppl. 1: 33Google Scholar
  88. 88.
    Sackett DL. Protection for human subjects in medical research. JAMA 2000; 283: 2388–9PubMedGoogle Scholar

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© Adis Data Information BV 2003

Authors and Affiliations

  1. 1.Department of Geriatric MedicineUniversity of Wales College of MedicineCardiffUK

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