When it comes to diversity in clinical trials, most discussions revolve around gender, race and ethnicity. If age comes up, the conversation tends to focus on pediatrics. But as the baby boomers age and life spans lengthen globally, some experts are recognizing a greater need to test investigational drugs and devices in the elderly.

Like children and adolescents, patients in their 70s and 80s have unique health issues that could affect a therapy's efficacy and risks. Changes in metabolism, weakened immune systems, memory issues, co-morbidities and a higher potential for adverse drug-drug interactions make the geriatric population more vulnerable than the typical adult patient enrolled in trials, Leslie Tector, a partner at Quarles & Brady LLP, told BioWorld Today.

While several countries, including the U.S., require sponsors developing therapies for pediatric use to conduct trials in the appropriate age group, they have no corresponding requirement for products that are likely to be used in elderly patients. And the FDA, which has offices focused on pediatrics, minority health and women's health, has no office specifically dealing with geriatric health.

But "there's a huge need" to consider the vulnerabilities of the elderly when testing new therapies, Tector said, as that's the age group with the greatest medical need. Physicians treating older patients need to know how therapies will work in this patient population, she added, so it's important to have that information, especially for conditions such as cancer, heart problems and diabetes that are prevalent in the elderly.

However, unless a drug is specifically targeting an age-related condition like Alzheimer's, it is tested in few older patients. As a result, most of the data about how a specific drug or device works in the elderly come from adverse event reports after the product has been approved, Tector said.

Speaking earlier this year on behalf of the American Heart Association at an FDA clinical trial diversity hearing required by the FDA Safety and Innovation Act, Rose Marie Robertson said that more than half of all trials for coronary artery disease in the past decade didn't enroll a single patient older than 75. Altogether, the geriatric population represented 9 percent of all patients included in the trials. (See BioWorld Today, April 2, 2014.)

A major factor impacting the number of older adults enrolling in trials is whether the trials are open to them. Over the past several years, there appears to be a marked increase in the percentage of trials that will enroll older adults – at least in those dealing with conditions prevalent in that population.

For instance, more than 85 percent of the phase III cardiovascular and tumor trials and 78 percent of the phase III metabolic disorder trials that started between 2012-2014 were open to adults 65 or older, according to Cortellis for Clinical Trials Intelligence. That's up from 2000-2002 when 77 percent of the cardiovascular trials, nearly 73 percent of the tumor trials and 67 percent of the metabolic disorder trials accepted subjects 65 or older. (See charts, below.)

The numbers are more telling when all trial phases in those three therapeutic spaces are considered, along with a further breakdown in age. While nearly 80 percent of all cardiovascular trials initiated between 2012-2014 were open to "aged" patients, those 65 to 80 years old, only 65 percent were open to "elderly" patients, or those older than 80.

The difference was even greater in metabolic trials. Whereas 72 percent of all metabolic trials would enroll aged subjects, only about 44 percent would enroll elderly adults.

DE FACTO AGE EXCLUSIONS

Appearances can be deceiving when it comes to clinical trials. A trial may be open to aged or elderly adults, but that doesn't mean it will actually enroll them. Many trials list other exclusion factors that effectively restrict the participation of older patients, Tector said.

In searching the Cortellis clinical trials database, Alvaro Arjona Saz, editorial director for drug development, Thomson Reuters, said he found that "common age-related disorders and ongoing medications are predominant in the exclusion criteria of trials enrolling aged adults."

For example, several non-insulin-dependent diabetes trials initiated in the past 12 months are open to aged and elderly subjects, but they often exclude subjects with tumors, heart conditions, renal disorders or other conditions common among older adults, according to the Cortellis data. (See Chart 1, below.)

Thus, the number of trials that actually enroll elderly adults may be lower than those that are open to older patients. And, unless a trial is specifically addressing an age-related illness or condition, the small percentage of elderly enrolled is not reflective of the targeted population. (See Charts 2-4, below.)

A case in point is Cubist Pharmaceuticals Inc.'s pivotal trials for Sivextro (tedizolid phosphate), which was developed to treat acute bacterial skin and skin structure infections caused by gram-positive bacteria, including methicillin-resistant Staphylococcus aureus (MRSA). Together, the two Sivextro trials enrolled a total of 1,324 patients; 69 of those patients, or about 5 percent, were 65 or older. Only about 1.5 percent, or 18 subjects, were 75 or older. Yet elderly patients, with more frequent hospitalizations and weakened immune systems, are among the most susceptible to MRSA.

"The inclusion of aged and elderly subjects in clinical trials presents several challenges associated mainly to medical and socioeconomic factors," Arjona told BioWorld Today. "These challenges may well justify the exclusion of aged adults during the design of some trials, but not in all cases."

One challenge is getting physicians on board, Tector said. Doctors often won't inform their older patients about trial options, especially if a patient doesn't have a life-threatening illness. Given their patients' overall health, doctors may question the benefit versus the risk of subjecting them to experimental or placebo procedures.

Another challenge is investigator buy-in. As it is, huge trials are logistically difficult, Tector said. Enrolling elderly patients can make a trial even more difficult for investigators. Mobility and other health issues could result in delays or cancellations of required visits and follow-up; memory problems could complicate patient-reported outcome measures; trial procedures, such as imaging, may be more complicated with older patients. And, in addition to the patient, the investigator might have to deal with a caregiver, adding another layer to the process.

"It's such a highly competitive market," Tector said of the clinical trial and regulatory approval process. "It's sort of a race for time." Subsequently, sponsors generally choose a healthier population so they can more easily demonstrate how their product works and more quickly satisfy regulatory requirements.

While it's ultimately up to the sponsor to decide which patient populations should be included in a trial, sponsors take their cue from regulators. Until regulatory agencies require and enforce age diversity in trials, there probably won't be much change. However, some countries, such as the UK, are beginning to recognize the importance of testing in older patients, Tector said.

In the meantime, sponsors and their clinical development partners should consider ways to overcome some of the obstacles so elderly patients aren't excluded from trials, Arjona recommended. "Medical factors such as comorbidities may be harder to tackle, but on the other hand they could arguably provide a better representation of the market in many scenarios," he added.