Medically speaking, if you are above the age of 65, you are considered an "older adult." On conducting rounds on the cardiology unit, I find it rare to see anyone less than 65 years of age. If someone below 50 years old gets admitted, they are almost considered "pediatric" from a cardiovascular perspective. Such observations reflect the realities of modern medicine. Patients are older, more frail, have multiple co-morbidities, and have complex social issues. During the next 25 years, the population age greater than 85 years will be more than double -- from 6.3 million in 2015 to 14.1 million by 2040. Yet for my older patients, when I prescribe medications for my heart failure, or use blood thinners to treat those who come in with heart attacks, I become wary. Many commonly used drugs have serious side effects such as increased risk of bleeding, renal failure, life-threatening electrolyte disturbances, and dangerous arrhythmias. Surprisingly, many of these drugs have never actually been tested in older patients. As a result, it is unclear if these drugs have any benefit or if they can cause serious harm in older adults.
Recently, I had a chance to discuss some of these issues with Dr. Karen Alexander, a cardiologist at the Duke Clinical Research Institute. Her research focuses on geriatric cardiology and she is currently on the leadership of the American College of Cardiology Geriatrics Council. She recently wrote an editorial on drug development in older patients. I asked if 65 years is really an appropriate cut-off with regards to calling someone an "older adult."
"Things really start to change for adults when they reach 75 years ... it is this group that we [physicians and drug developers] need to be thinking about."
Back in 1989, the Food and Drug Administration set out non-binding recommendations on how older adults could be included in clinical trials. However, almost two decades later, the elderly continue to be excluded from randomized trials.
"In earlier trials there used to be very clear exclusions, where trial protocols who exclude those above 75 or 80 years of age," says Dr. Alexander.
Currently the proportion of trials with such explicit cut-off are declining, but trials may have other inclusion and exclusion criteria that make it difficult to enroll older patients. "Exclusion criteria such as inability to make clinic appointments, renal dysfunction, or diagnosis of a cancer even it was treated and no longer active, often preferentially exclude elderly patients." Logistically, it is more challenging to enroll elderly patients in clinical trials. "It is harder to get older patients to understand what you are doing. There are often other family stakeholders that have to be brought it. Often [elderly patients] are not driving themselves, so these become factors that limit the participation of elderly patients in clinical trials."
Doctors and nurses who enroll patients in clinical trials may overlook the elderly because of subjective feelings that the patient may be harmed in a trial. The consequences of excluding elderly patients from clinical trials are significant and results in a substantial lack of evidence for therapies in elderly patients who present with cardiovascular diseases such as a heart attack or heart failure. Such patients, who are often at the highest risk of dying, may stand to gain the most benefit from drugs and cardiac procedures; however, the potential for harm may also be exaggerated in this frail population.
Dr. Alexander states that "we have to extrapolate data of drug safety and efficacy from a much younger population."
In effect, we do not know if many of the drugs we commonly use today, work or are safe in older patients.
Simply making guidelines recommendations have not resulted in a significant increase in elderly patients being enrolled in randomized trials. There are some potential solutions. The FDA has a number of dedicated offices relating to special populations such as the Office of Women's Health, Office of Minority Health, and Office of Pediatric Therapeutics. Congress could create an Office of Geriatric Health and Aging which would allow for the needs of the elderly to be represented in clinical trials. The National Institutes of Health sponsored trials have targeted enrollment for sex, race, and ethnicity -- similar age-based targets for trials can be adopted. Every drug approved by the FDA has a specific drug label which outlines how and when that particular drug should be used. Companies that have demonstrated safety and efficacy of drug therapy in the elderly population can highlight this data in the FDA drug label. Therapies that have clear evidence of benefit with minimal harm in an older population should receive preferred payer status in Blue Cross or Blue Shield. The Center for Medicare and Medicaid is another big stakeholder that can help to drive companies into doing more studies in the elderly.
"CMS should demand this [evidence in older patients] and should be paying for treatments that have shown benefit in elderly patients," advocates Dr. Alexander.
Another more controversial strategy involves incentivizing the patent protection extensions. Drug development is a very expensive process as a majority of potential drugs studied never make it to market. The Pediatric Exclusivity Rule of 1997 allowed for a 6-month patent extension for conducting studies in children, which resulted in a significant increase in the pediatric labeling of drugs. Patent exclusivity targeted towards the elderly may provide an opportunity to increase knowledge in elderly patients while providing companies an incentive to conduct dedicated trials.
Over the past few year, progress has been made. Now more than ever, older patients and their advocates have the ability to get involved in the drug development process. Patients have a greater say in which FDA-regulated products are included in their own care as a result of new patient-engagement initiative. The Patient Engagement Advisory Committee and the Patient-Focused Drug Development initiative from the FDA highlights some of the pathways that patients and patient advocacy groups can influence drug development policy. Through the Patient-Reported Outcomes Measurement Information System program, the National Institutes of Health has also developed a knowledge base of outcomes that are relevant to patients. In addition, more studies are focusing on the role of intervention in elderly patients. As an example, transcatheter aortic valve replacement (TAVR) is a method to replace aortic valves typically using catheters and wires through the major vessels in the groin. While expensive to conduct, this procedure often can be done instead of an open heart surgery. TAVR can be very useful in older patients who may not tolerate open heart surgery but the benefit in this older patient population is not as clear. Using large databases, researchers have examined the usefulness of TAVR in nonagenarians and identified that quality of life significantly improves even in this older patient cohort.
As a next step, patients, payers, doctors, and pharmaceutical companies need to work together to ensure that the elderly are represented throughout the drug development process. Physicians are often in the dark when it comes to treating the older patients. As our population ages, we need to ensure that we are actually helping, and not harming, older adults.
Disclosures: No disclosures relevant to this article.