(Almost) healthy old folks in clinical trials
(Almost) healthy old folks in clinical trials
Both regulatory authorities and other guidance such as ICH strongly recommend including elderly patients into clinical trials wherever a disease is prevalent in the higher age bracket. The reasons for this are many: there is a trend to an aging population, pharmacokinetic properties of drugs may change with age (e.g. by age-related decreases in renal or hepatic function), and individual reactivity may, independent from pharmacokinetics, change as the patient grows old.
So far, elderly patients were included into the “regular” trials wherever possible, and unreasonable upper age limits were either totally removed or extended liberally. Some studies stratify by age in order to enroll a reasonable proportion of, say, patients above 75 years of age. In other cases, special studies are done in elderly populations, usually defined as above 65 years of age.
In reality, many of our clinical trials already contain an elderly proportion higher than is usual in the diseased population as such. The main reason for this are highly complex trials demanding many patient visits, some of them extended – something which elderly patients can do as they are no longer part of the working population; sometimes, they even seek trials for “social reasons”.
One might conclude that thus studies in geriatric populations are no issue anymore. Nothing could be more wrong. The eligibility criteria in trials are the same for them as they are for young patients. Therefore elderly patients qualifying to participate in trials are a highly selected group, usually not suffering from any other major disease and not receiving significant other medication. They usually do well in trials - which does not come as a surprise. Their retention is comparable to that of younger subjects, and the incidence of serious adverse events is not much higher. Whether this selection also is responsible for a very high compliance is not easy to explore.
The “typical” elderly patient, with several co-morbidities and other drugs on board, is not admitted to such trials. In particular in long-term studies, patients’ life expectancies sometimes are part of eligibility.
Even in some recent evaluations of marketing authorization studies, analysis by age group is not frequent. An examination on how valid the age group is – are those patients truly representative – is rarely given. Many of the ideas brought up in the 1990s such as population pharmacokinetics, are not given too much attention.
While it is laudable that more elderly patients get into clinical trials, the knowledge on actions and side effects in the “real” elderly is difficult to anticipate in many cases. Unless more refined measurements including simple trough drug levels (or methods of sparse sampling) are used, potentially dangerous dosing or interaction incidents will occur without any warning.