Old moves

The age-old challenge of diversity in clinical studies

Over the past few years, we have seen an increasing focus on ensuring the diversity of patient populations across clinical trials.

This is hugely important, as gathering data from a diverse group ensures that results from these studies better reflect the realities of society and the patients that the industry is seeking to help.

The recent International Day of Older Persons presented a timely opportunity to consider age diversity, an often-overlooked aspect of diversity in clinical trials.

Medicines are often under-tested in older patients, and it is vital to address this gap in clinical data, particularly against the backdrop of an increasing older population, to ensure that regulators and doctors are able to make the right approval and prescription decisions for older patients.

Clearly, the main purpose of the majority of clinical trials is to assess the safety and efficacy of a drug within a defined patient population. Older adults represent a hugely relevant demographic for drug development.

In 2019, it was estimated that 9% of the global population was aged 65 or over, and this figure is expected to grow over the coming decades. This makes it all the more important that we put frameworks in place to ensure that this growing group is fully represented in clinical research.

Some diseases affect patients of a certain demographic more than others, and older adults represent a significant proportion of those suffering from certain illnesses. For example, 42% of oncology patients are over the age of 70, yet this age group makes up only 24% of participants on oncology trials registered with the US Food and Drug Administration (FDA).

This discrepancy can impact the validity of clinical research, because trialling drugs in non-representative populations creates a risk that the data will not accurately reflect safety and efficacy of the drug in the people it is designed to help.

There are two important points to consider when we think about the need to incorporate older people into clinical trials.

The first is age-related changes in organ function and body composition, which have the potential to alter the pharmacokinetic and pharmacodynamics of a drug in older populations.

The second is that older people are much more likely to be taking other prescribed medicines, with a high proportion of trial participants over the age of 65 receiving three to five concomitant medications. This can be a cause of concern for researchers and a barrier to participation, as increasing the risk of drug-drug interactions in a clinical trial is perceived to limit the validity of its findings.

Consequently, trials often impose upper age limits on participation to reduce this risk. However, it can be argued that enrolling patients with a range of comorbidities and already taking various medications can in fact enrich the utility of the research.

When the drug comes to market, it will have already been assessed in patients taking different medicines, thereby reducing the risk that the drug could negatively interact with these treatments in a real-world setting.

Regulators recognise the importance of age diversity in clinical trials. The FDA’s 1997 guidelines state that older populations should be represented sufficiently ‘to permit the comparison of drug response in them to that of younger patients’, and US guidelines require a minimum of 100 patients over the age of 65 in clinical trials for diseases present in the older population.

The FDA’s draft guidance on the inclusion of older adults in cancer clinical trials also stresses the importance of studying drugs in individuals aged over 75. It suggests that sponsors may want to consider conducting specific trials designed to recruit only older patients, rather than having them as a subgroup of the overall trial patient population.

While this new guidance is a promising step forward that recognises the needs of older patients, its adoption may be limited without more stringent requirements for companies to comply.

Alongside concerns amongst researchers about the suitability of some older people for trials, as we enter an increasingly digitalised world, generational challenges when it comes to using new technology can also be a large barrier to their participation.

In recent years, particularly since the COVID-19 pandemic, we have seen a huge increase in decentralised clinical trials (DCTs), which use technologies such as electronic patient diaries and wearables to allow patients to participate in clinical research from their own home.

DCTs can be an incredibly powerful tool in helping to open up trial participation to a more diverse pool of patients, as they remove the need for patients to travel to a trial site. This is particularly beneficial for those with mobility issues, or who live far away from trial sites.

Older populations, however, can be more cautious when using new, unfamiliar technologies involved in clinical trials, may not have internet access, or may find it difficult to use screens or wearable devices.

It is therefore important to ensure that the use of any technology is as simple and user-friendly as possible, and that patients who experience difficulties are offered alternative options.

In addition to designing trials to address all levels of technical literacy, it is important that any trial involving a decentralised element still maintains empathy and a ‘human touch’. Enrolling in a trial is a huge undertaking for any patient and can be overwhelming, particularly if it involves unfamiliar technology or processes.

Therefore, it is important to ensure that patients still have access to an expert – not just an automated chatbot – who can answer any questions that they have and provide reassurance if needed.

As the global population continues to age, it will become more important than ever to ensure that older people are a key part of clinical research. Regulation will be crucial, and while the current FDA guidelines are a good start, raising awareness of the value of age diversity and incentivising companies will help to drive the change. Tight regulation can often catalyse the industry into early conversations to embed the right policies into clinical trial design.

Ultimately, we must prioritise the patient experience ahead of meeting regulatory guidelines, with the industry simplifying the clinical trials process as much as possible for patients so they feel supported throughout their trial journey.

Alicia Staley, VP, Patient Engagement at Medidata. Go to medidata.com