Age-based Exclusions in Clinical Trials

Elderly subjects often are excluded from clinical trials due to age-based exclusion criteria. However, age is only a surrogate. The reasons for the exclusions of this population should be supported by scientific and ethical rationale and justified with regards to the risk/benefit ratio and objectives of the research. Otherwise, excluding the elderly from clinical trials misses the opportunity for this population to receive benefits, and obtain important knowledge.

1. What factors are causing age-based exclusions to be possibly inappropriate or unnecessary?

Factors which are possibly inappropriate or unwarranted include^1,2,3:

• Exclusions based on arbitrary age-based criteria without any scientific or ethical rationale as a shortcut to reduce risk
• Confounding co-morbid factors that are more prevalent in the disease being researched but may not affect the risk/benefit ratio
• Fear of increased financial burden and time spent in older subjects enrollment, retention, completion of study-related activities, and management of research-related injuries.

2. What is the role of IRBs to ensure older populations are included in clinical trials?

If research is being conducted for an indication that is prevalent in older populations, it is important, scientifically, and ethically, that an attempt should be made to include older populations in the research and not to have arbitrarily restrictive age-based exclusion criteria. These older individuals may have the potential for direct benefit and their participation in the study may provide important knowledge for their representative population. Based on the Belmont report basic ethical principles (Belmont report), and IRB criteria for approval (21 CFR 56.111, 45 CFR 46.111), there should be equitable selection of subjects so that those bearing the burdens of research will have potential for direct benefit and represent those who will benefit from the knowledge gained. IRBs should ensure that the study includes adequate safeguards and protections as well as reasonable accommodation and assistance to allow inclusion of older subjects.

3. What is the role of Sponsors or study investigators? What should they consider about the age-based exclusion criteria in their protocols?

The Sponsor needs to carefully design the study inclusion and exclusion criteria based on justifiable scientific background and objectives of the study without a reliance on arbitrary age-based exclusions. They can also support individual sites to have adequate safeguards, assistance, and provisions in place to conduct the study with older individuals.

Considering an older subject population may have co-morbid conditions, and functional impairments, Site Investigators should endeavor to develop the sufficiency of support staff, funding, and available resources to support older person’s:

• recruitment and retention success,
• safe conduct of study related activities,
• management of adverse events considering possible disabilities, and
• accessibility for those with functional impairments.