Trial Organizers Must Involve More Older People in Research

Much has been said and written during the past year or two about the urgent need to conduct more pediatric clinical trials, but a less fashionable topic is the importance of including older people in clinical research.

Marion E.T. McMurdo

In an editorial in the British Medical Journal on 5 November 2005 (BMJ, 331, 1036–1037), an eminent Scottish geriatrician presented a compelling case for involving the elderly in more trials. Prof. Marion E.T. McMurdo, head of ageing and health at Ninewells Hospital and Medical School in Dundee, UK, argued that the benefits shown in trials in younger people may not apply to older people.

In the following question-and-answer article, she elaborates on this subject.

Q. Why are the elderly in need of clinical trials specifically geared to this age group?

A. Older people comprise almost one in five of the population of most developed countries, yet are systematically excluded from participation in clinical trials. To be able to provide the most effective treatment and management for our growing older population, we must have good quality trial evidence to underpin this. The lazy option of simply extrapolating results from younger populations may be very misleading.

Q. What special problems exist when conducting clinical trials in the elderly?

A. There may be particular issues relating to communication—deafness, visual, and cognitive impairment are relatively common in older age groups. Older people will often have a range of comorbidities (and concomitant medication), which may make trial results less "clean." Practical issues about transport, mobility, and access should also be considered.

Q. Does the informed consent process need to be changed for the elderly population? If so, what do you suggest?

A. I don't think that older people need any special process for informed consent. Researchers should, however, be sensitive to the fact that older people may wish time to discuss possible trial participation with family and friends. However, it is encouraging to note that older people report a high rate of willingness to consider trial participation when approached.

Q. You mention in the BMJ editorial that protocols need to be specifically designed for the elderly, or modified exclusion criteria should be used to allow inclusion of patients with comorbid disease and multiple medication. Has this been done elsewhere, and has it been shown to work successfully?

A. Many of the major clinical trials worldwide have recruited middle-aged men with a single pathology, and no concomitant medications. But in the real world, typical heart failure patients for example are over 75 years of age, female, with numerous comorbidities and are in receipt of multiple medicines. It must be possible to ensure that more protocols are designed in a way that permits the inclusion of the population most likely to be prescribed the drug once licensed.

Q. Which adverse reactions tend to occur most frequently in elderly subjects, and how should they be handled?

A. The type of adverse events will depend to a large extent on the type of compound under evaluation. However, it is known that prescription of psychotropic drugs, for example, is associated with an almost doubling in the risk of falling in older people. I would welcome the development of trial protocols evaluating such compounds that specifically seek to systematically record falls rates.

Q. What practical actions can investigators, sponsors and contract research organizations take in order to overcome the special problems of the elderly population?

A. I prefer not to think of the elderly population as having "special problems." They are just people who have had rather a lot of birthdays. Unfortunately, this deters investigators from including them in clinical trials. Rejection proposals intending to set arbitrary and unjustified age restrictions as unethical would be an excellent starting point.

Q. Overall, what suggestions or recommendations can you offer the global pharmaceutical industry regarding inclusion of the older population in clinical research?

A. Cardiovascular disease, cancer, and diabetes are diseases that affect large numbers of older people, yet the depressing fact is that at present the older population is being deliberately excluded from participation in the major clinical trials in these key areas. The pharmaceutical industry should devise trial protocols targeting trial populations who are most likely to be prescribed the medication once licensed. This will confer the advantage that the trial results will be more generalizable. Conferring with specialists in old age medicine about trial design might make this process considerably easier. We need to start getting this right for today's older people, and don't forget that very soon we too will be joining the ranks of the older population.