Planning for our future: participation of the older population in clinical trials
Why are older people so often excluded from clinical trials? Is this a cause for concern?
The world is ageing. By 2050, the number of people aged 65+ will be 16% of the global total, coming from only 8% in 2010.1 While this trend can be considered a triumph of medical, social and economic advances, it also causes big challenges. We have often heard about how the ageing population strains insurance and pension systems. But there are also other consequences which may be less well known. One of these is related to the testing and use of medicines. People over 65 make up the majority of patients for many medications intended to treat chronic conditions, but typically those who are over age 65 are excluded from participating in clinical trials. Should we be worried about this?
Twenty years ago, an important global event called the International Conference on Harmonisation (ICH) laid out a compelling case for including people aged 65+ in all clinical trials for treatments aimed at adults. It argued that results from trials studying only younger adults may not be relevant to older people, whose bodies are quite different.2 Yet this is exactly what is still happening in daily medical practice today: clinical decisions for older adults are routinely based on data from studies of younger people. In these situations, doctors are left to treat older patients without knowing how well the chosen drug works in this population, how it behaves in their bodies, what side-effects it may cause, what doses are best, and to what extent it may interact with other drugs being taken.
The world is ageing. While this trend can be considered a triumph of medical, social and economic advances, it also causes big challenges.
The issue of side effects is a good example. Many studies show that the older you get, the more likely you are to experience side-effects from drugs.3 The reasons for this are complicated but may be attributed to the fact that the way drugs pass through the bloodstream, reach the tissues and are excreted (termed ‘pharmacokinetics’) changes with ageing.4 People also tend to take more medicines as they get older.3 A US article reports that about 50% of the over-65s take at least five different drugs.5 And unfortunately, the side-effects of one drug can sometimes boost the side effects of another.3
So how bad is the problem of under-representation of people aged 65+ in clinical trials? Here is one example: only about 25% of participants in cancer trials are older people, despite the fact that two-thirds of cancer patients are 65 or older.6 This one is even more surprising: older people are consistently under-represented in trials for Alzheimer’s disease, even though it’s well known that this is nearly always a disease that affects older people.6
A study looking at trials published from 1994 to 2006 found that in nearly 40% of those trials, people over the age of 65 had explicitly not been deemed eligible to participate.7 And even when older people aren’t excluded because of their age, they get left out for other reasons. More than 45% of the trials that didn’t have age limits, excluded people for reasons like taking other medications, having other illnesses or physical disabilities, or even for living in a nursing home – all restrictions that tend to remove older people from the clinical study population.7
Admittedly there have been good reasons why people older than 65 have been excluded from trials:
- As mentioned before, older people are at greater risk of drug side-effects, which can be serious. When this happens in a clinical trial, the patient may have to drop out of the trial which is always a problem for research teams.
- When a patient has several medical conditions – as older adults often do – this can make trial findings ‘messier’ and more difficult to interpret, which means the trial may end up being less valuable.
- There are also various practical challenges: such as supporting older people with transportation to the study clinic, and the need for carers to be involved in helping the patient to comply with the trial requirements.
But these issues should be seen as challenges, not excuses. It will also become harder to side-line the older population in clinical research because Regulatory Authorities (the authorities who license new medications, such as the US Food and Drug Administration (FDA)) are tightening up. Some people think drugs for chronic diseases that are not adequately tested in people over 65 years old may soon not make it through the approval process.8
A New Definition of ‘Older People: 75 Is the New 65
Of course, older people are not the only group to have been consistently under-represented in clinical trials. A similar situation existed with women and also with children. However, the FDA has announced its position has “evolved from a view that we must protect children from research to a view that we must protect children through research.” 9
Many experts and policymakers recognize a need to adjust the definition of ‘older person’ from 65+ to 75+ to reflect the ageing of society.10 By continuing to exclude the over-65s, those who design and fund clinical trials could be living in the past.
- ICH. Guidance for Industry: E7 Studies in Support of Special Populations: Geriatrics. Questions and Answers. February 2012, ICH.
- Routledge AP, O’Mahony MS, Woodhouse KW. Adverse drug reactions in elderly patients. Br J Clin Pharmacol 2003, 57(2): 121-6.
- Herrera AP, Snipes SA, King DW et al. Disparate inclusion of older adults in clinical trials: priorities and opportunities for policy and practice change. Am J Public Health 2010; 100(Suppl 1): S105–S112.