May 4, 2020
National Center for Health Research’s Public Comments on FDA’s Proposed Inclusion of Older Adults in Cancer Clinical Trials Guidance for Industry
[FDA-2019-D-5572-0002]
We are writing to express our views on the FDA Draft Guidance on Older Adults in Cancer Clinical Trials. The National Center for Health Research (NCHR) is a nonprofit think tank that conducts, analyzes, and scrutinizes research, policies, and programs on a range of issues related to health and safety. We do not accept funding from companies that make products that are the subject of our work.
We have long urged the FDA to require older adults in clinical trials of drugs for the treatment of cancer and other diseases that are likely to be used by people over 65. When our Center’s president served on CMS’ Medicare Evidence Development & Coverage Advisory Committee (MEDCAC), she pointed out at every meeting that there were few if any patients over 65 who had been tested in clinical trials for the drugs and devices that were seeking to be covered by Medicare. As a result, it was impossible for the MEDCAC members to determine if the likely benefits outweighed the risks of any of those products, including cancer diagnostic tests and treatments.
We strongly support FDA’s efforts to improve the diversity of clinical trials and analyses of demographic subgroups, but have been disappointed that these efforts have not been enforced in a meaningful way. Subgroup analyses of safety and efficacy are essential for new drugs and devices so that patients and clinicians can make informed treatment decisions. New medical products should only be approved for populations for which there has been sufficient testing to determine that the benefits outweigh the risks. This is of particular importance for older adults in cancer trials. Moreover, if the FDA refused to approve cancer drugs for patients over 65 or over 70 when those age groups were not adequately studied, it would provide a substantial incentive for sponsors to be more vigilant about recruiting and studying patients in older age groups.
As stated in the guidance, it is not sufficient to only study the safety and efficacy of treatments among younger adults and assume that the results would be the same for older adults as well. We also strongly support the recommendation to evaluate smaller, discrete age groups (such as ages 65-74 and 75 and up), as well as the recommendation to collect additional safety measures for older adults, such as cognitive functioning. However, there are additional aspects of subgroup analysis that must be taken into consideration.
Subgroup analysis must determine the unique benefit to risk ratio for each subgroup, rather than determine whether the benefits of a treatment differ between younger and older patients. Older adults are more likely to have comorbidities that can affect how drugs are absorbed, metabolized, or eliminated, which may impact the safety and efficacy of a particular treatment. Therefore, there must be an assessment of the unique risks and benefits for older adults. It is not important to know that a medical product is more or less safe or effective for older patients compared to younger patients; what matters to older patients is whether the benefits outweigh the risks for patients in their age group.
In addition, it is not necessary that the proportion of older patients studied is consistent with the proportion of older patients with the particular type of cancer. What matters is that there be sufficient numbers of older adults so that subgroup analyses can be conducted to assess the benefits and risks of treatment for patients in several older age groups. Subgroup analyses are not meaningful if the numbers of older patients in the trials are small.
Since older adults are likely to be more frail and to have other serious comorbidities, it is imperative to determine the adverse effects and the efficacy of new drugs for older adults prior to FDA approval. All too frequently, post-market research, even if required, is delayed, follow-up is inadequate, or for other reasons the results are not as informative as had been expected.
The National Center for Health Research can be reached at info@center4research.org or at (202) 223-4000.