Elderly subjects can benefit clinical trials
Studies show elderly are often excluded
Researchers and physicians are increasingly speaking out on the issue of the geriatric population being excluded from clinical trials.
A 2011 study in the Journal of General Internal Medicine looked at phase III and IV studies conducted in 2007. The research team focused on the age limits of the study and the reasons for exclusion.1
"One of the major findings was that 20% of the clinical trials excluded patients on age alone, and nearly half of remaining trials excluded adults that have complex conditions," says Donna Zulman, MD, instructor in the division of general medical disciplines at Stanford University, and physician investigator at the Center for Health Care Evaluation at the Veterans Administration Palo Alto Health Care System, and the study's lead author.
Other studies in the analysis had eligibility criteria that disproportionately affected older adults, including medical comorbidities, those living in nursing homes, and physical disability or functional limitations.
"I think it's extremely important for IRBs and funding agencies and the FDA to accept this issue and ensure that, when it's possible, to include geriatric patients, and that age exclusions are for good reasons," Zulman said. "We want to make sure those individuals are well-represented."
Geriatricians and primary care physicians have found it difficult to care for their geriatric patients with new medications. Physicians proceed with caution when prescribing new medications that do not include evidence as to how the drug will affect an older person's system, or interact with other medications.
"Many of my patients are older and have multiple chronic conditions," Zulman says. "The information out there isn't always relevant. Physicians are using more art than science to understand what will work best with patients."
The study concluded, "Clinical trial evidence guiding treatment of complex, older adults could be improved by eliminating upper age limits for study inclusion, by reducing the use of eligibility criteria that disproportionately affect multi-morbid older patients, by evaluating outcomes that are highly relevant to older individuals, and by encouraging adherence to recommended analytic methods for evaluating differential treatment effects by age."1
"There's a lot of potential there"
As the baby boomers age and near retirement, the health care system will see an ever larger increase of seniors taking medications. The Population Resource Center estimates that the number of people age 65 or older will double by 2030.2 The over-65 population accounts for about 60% of healthcare expenditures. Life expectancy is increasing rapidly, and one in five Americans will be 65 or older by 2030. With the older population growing quickly, the need for new medications and an understanding of how they will affect an older population is growing more urgent. In 2005, the American Geriatrics Society found that more than 900 drugs in the trial stage were aimed at treating conditions associated with aging.3 However, some physicians express frustration that elderly subjects are excluded from trials, and would like to see IRBs insist upon elderly inclusion.
"There will be more elderly in a study if there's a requirement," says Diana Zuckerman, president of the National Research Center for Women & Families Cancer Prevention and Treatment Fund in Washington, DC. "If the folks doing the study are told to include the elderly, it will happen. They will do what their doctors suggest. I don't think there will be an 80-year-old more stubbornly refusing than a 40-year-old. Someone who is 80 years old would be less afraid, and more likely to just go along with whatever the doctor suggests. I think the issue is an IRB saying, let's make sure patients in the study are patients who will benefit from the intervention and not just open it to people to a certain age — some percentage [participants] must be in this age group."
One factor in excluding subjects above a certain age is that researchers are looking for the best results from a drug — studying its effects in people with only one condition and focusing just on that condition. And it's not always feasible to include elderly subjects if they are too fragile or the drug too risky.
"The part about this that is understandable and appropriate is that it's easier to understand a product that is used on patients who are healthier, so the study is on patients who have one condition only," Zuckerman says. "But this is not true in the real world. People have a lot of different health problems that are going on at the same time, especially in people over 70.
"I think that IRB folks should care very much what the age range is and what the protocol requirement of comorbid conditions are," Zuckerman continues. "Drugs and devices are tested on people younger and healthier than many of the people who will use it. Those results may be overly optimistic about effectiveness."
As a result, many new drugs are prescribed to older patients who may have many comorbidities and are taking several other medications, without knowing how the new drug will interact. Metabolic systems vary and are more fragile.
For example, a new osteoporosis drug "is being given now to a large number of older people and we have no idea how it will act in an older population," says John Morley, MD, director, division of geriatric medicine at Saint Louis University. "Drug companies will tell you that if you put an older person in, the chance of side effects will go up significantly. They want to tell the FDA that a drug is fundamentally safe. They are not drug side effects, just side effects that occur in people with lots of events [comorbidities]."
Zuckerman cites medical devices, such as gastric bands or replacement hips and knees, that may not have been tested in people over 65. "Are they ever tested, and is there a difference for people over 65? If studies don't include those people, how do you know? The effects might be good in the short run, but not in the long run.
"There are numerous instances of Medicare paying for devices tested on younger people with no evidence that they are good for older people," Zuckerman says.
Morley has found there is much willingness among geriatric patients to be part of clinical trials. "There is a lot of interest there as a whole," he says. "If it's a complex trial and the person is very frail, that's different, but in general it's very easy to enroll this population in trials."
Transportation and costs are other barriers to participation by elderly people. Medicare has tried to ease those burdens by paying for routine costs of items and services, including room and board, costs of device implantation, and treatment of side effects and complications. However, Medicare beneficiaries must cover the costs of coinsurance and deductibles, as well as the new item the study is testing.4
Morley has seen success with trials that have included older patients. "Occasionally you do see drugs being tested in people to the age of 85, and with positive results," Morley said. "There's a lot of potential if you do it."
References
- Zulman DM, Sussman JB et al. Examining the Evidence: A Systematic Review of the Inclusion and Analysis of Older Adults in Randomized Controlled Trials. J Gen Intern Med 2011 26:783-790
- Population Resource Center. The Aging of America. http://prcdc.org/300million/The_Aging_of_America/
- American Geriatrics Society. http://www.americangeriatrics.org/files/documents/Older_Adults_in_Clinical_Trials_FINAL.pdf
- Centers for Medicare& Medicaid Services. http://www.medicare.gov/publications/pubs/pdf/02226.pdf
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