Age Equity, Diversity & Eligibility for the Healthy Volunteer
Diversity, Equity & Inclusion
Many healthy volunteers encounter eligibility criteria related to age, sex, gender identity, reproductive or childbearing status, nationality, and other demographic characteristics.
While some restrictions may be supported by legitimate scientific, medical, or safety considerations, participants are not always provided with a clear explanation regarding why certain groups are included or excluded from specific studies.
HVA supports greater transparency and consistency regarding demographic eligibility criteria and believes research organizations should clearly communicate the rationale underlying significant exclusion requirements to help ensure fairness, accountability, and equal treatment throughout the clinical research process.
HVA believes research organizations should be held to the same principles of diversity, equity, inclusion, and non-discrimination applied in other settings unless demographic exclusions are supported by legitimate scientific, medical, safety, or regulatory justifications.
Age Equity & Eligibility
Age limits are often set for administrative or historical reasons, not because older adults are unhealthy or unsuitable for research participation.
Healthy volunteers over the age of 45, and often well into their 50s and 60s, routinely pass initial clinical screening requirements, including blood pressure checks, ECGs, and standard urine screening.
The Evolution of Diversity, Inclusion & Representation in
Clinical Research
Before the 1970s: Prisoners as Research Subjects
For much of the 1950s, 1960s, and early 1970s, prisoners were commonly used in clinical research because they were viewed as a convenient and accessible study population.
Growing ethical concerns regarding informed consent, coercion, and participant protections eventually led to significant reforms that greatly restricted prisoner participation in biomedical research.
1977: Women Largely Excluded from Early Drug Research
FDA guidance recommended excluding women of childbearing potential from Phase I and early Phase II drug studies due to concerns about potential risks to unborn children.
Although the guidance was intended to protect women and fetuses, it resulted in many women being excluded from clinical research for years afterward.
As a result, much of the clinical research conducted during this period relied heavily on younger male participants, creating gaps in understanding how drugs affected women differently.
1986: NIH Begins Addressing Inclusion
The National Institutes of Health (NIH) adopted policies encouraging the inclusion of women and minority populations in federally funded clinical research.
However, implementation was inconsistent, and many studies still lacked adequate representation.
1993: NIH Revitalization Act
A major turning point occurred with the NIH Revitalization Act of 1993.
The law required women and minorities to be included in NIH-funded clinical research unless there was a clear scientific or medical justification for exclusion.
Researchers were also expected to analyze whether treatments affected different demographic groups differently.
This legislation is widely considered one of the most important milestones in the effort to improve diversity and representation within clinical research.
Late 1990s: Present Expanding Representation
Over time, clinical research has increasingly emphasized the inclusion of women, racial and ethnic minorities, older adults, and other historically underrepresented populations.
Today, regulators, researchers, patient advocates, and industry organizations continue working toward ensuring that study populations more accurately reflect the people who may ultimately use approved therapies.
Current Discussion: Age Equity & Transparency
While progress has been made regarding representation, questions remain about age-based eligibility criteria and demographic exclusions.
HVA recognizes that some exclusions may be supported by legitimate scientific, medical, safety, or regulatory considerations.
However, participants are not always provided with a clear explanation regarding why certain demographic groups are included or excluded from specific studies.
HVA supports greater transparency regarding demographic eligibility criteria and believes research organizations should clearly communicate the rationale underlying significant exclusion requirements.
Industry Perspective: Merck's Diversity, Equity & Inclusion Initiative
Merck publicly acknowledges that healthy volunteers may encounter eligibility criteria related to age, sex, gender identity, reproductive status, nationality, and other demographic characteristics.
Merck notes that while some restrictions may be supported by legitimate scientific, medical, safety, or regulatory considerations, transparency and inclusion remain important components of modern clinical research.
HVA believes Merck's discussion highlights the growing recognition throughout the research community that diversity, representation, and participant understanding are important considerations in study design and recruitment.
Age and Fair Access to Screening
HVA does not claim that any age group makes “better” research participants.
What we do believe is that healthy adults should be evaluated based on their actual health, not excluded based solely on age!
Many volunteers over the cut-off ages of 45, 50, 55, 60 and beyond meet the same baseline health requirements as younger adults, including blood pressure, ECGs, and initial screening criteria.
Clinical research benefits when eligibility decisions are based on individual health rather than age alone.
When arbitrary age cutoffs are used, otherwise qualified healthy volunteers are excluded without being given the opportunity to participate.
HVA supports inclusive study design that evaluates volunteers on medical criteria, not exclusion based on age.
Age-based exclusions often fail to reflect actual health status. Many individuals who are older but not taking medications for chronic conditions such as hypertension, diabetes, cardiovascular disease, or other age-associated illnesses are, by definition, healthy.
At the same time, a substantial portion of the general adult population is ineligible for healthy volunteer studies due to medication use, smoking status, or other protocol defined lifestyle factors, which significantly limits the available pool of eligible participants.
As a result, excluding older volunteers solely based on age is a moot point: individuals who are medically ineligible are already screened out by standard protocol requirements, while healthy older adults who meet all eligibility criteria are denied the opportunity to screen.
This approach is neither scientifically sound nor aligned with the realities of modern clinical research, particularly as many investigational therapies are intended for conditions that primarily affect older populations.
Evidence on Age Inclusion in Clinical Trial Representation
Clinical research authorities and peer-reviewed studies demonstrate that excluding participants based solely on chronological age often limits the scientific validity and generalizability of study results.
Rather than age itself, a person’s individual health status, functional capacity, and screening outcomes are more accurate and appropriate determinants of research eligibility.
Evidence from Clinical Research Policy and Analysis Shows:
Regulatory Guidance Encourages Age Inclusivity
Federal research policy emphasizes that age alone should not be used as a default exclusion criterion in clinical research.
Across the lifespan framework, inclusion policies require that age-based exclusions be scientifically or ethically justified.
Researchers are expected to include individuals of all ages, including older adults, unless there are compelling, evidence-based reasons not to do so.
Age as a Surrogate, Not a Proxy for Health
Industry and academic analyses consistently report that arbitrary age-based exclusion criteria, when not supported by scientific or ethical rationale, can result in missed opportunities to study treatment effects and safety in relevant populations.
Chronological age alone is not a reliable indicator of health status, functional ability, or trial suitability.
FDA and OHRP guidance does not require the routine inclusion of healthy older adults in clinical research, leaving eligibility decisions largely to sponsors and IRBs.
The American geriatric society states that older adults must be adequately represented in research trials to ensure that study findings are meaningful, applicable, and reflective of real-world patient populations.
Underrepresentation of Older Adults in Clinical Trials
Analysis of NIH-published research demonstrates that older adults are frequently underrepresented in clinical trials, using COVID-19 studies as a clear example of a broader long-standing issue in clinical research.
The authors note at that exclusion or limited enrollment of older adults is frequently driven by established trial design practices and eligibility criteria, rather than clear scientific or clinical justification, resulting in study populations that do not adequately reflect real-world patients.
The authors caution that this mismatch can limit the safety, applicability, and external validity of study findings, raising concerns that extend beyond COVID-19 studies but reflect broader patterns seen across many clinical trials.
Industry Analysis: CenterWatch on “Age Based Exclusions in Clinical Trials.”
For full Center Watch analysis on age based exclusions in clinical trials -click the link below.
For information on WCG-A global clinical Research Services company- Click on the WCG/CenterWatch logo above.
While this section focuses on age, similar concerns also apply to other eligibility criteria, including sex, ethnicity, and childbearing status, which can limit participation without clear or consistent justification.
~~~IMPORTANT~~~
Scientific evidence shows that healthy older adults are physiologically different from younger adults.
These age-related differences affect how the body absorbs, metabolizes, distributes and eliminates medications at different rates.
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How Aging Changes Drug Processing in Healthy Adults:
With aging, liver metabolism and hepatic blood flow often decline, which can change how quickly a drug is broken down and how long it remains active.
Kidney function (eGFR/creatinine clearance) also commonly declines, which is critical for drugs that are cleared through the kidneys and can raise the risk of higher exposure or accumulation even when someone is otherwise healthy.
Older adults also have predictable shifts in cardiovascular physiology.
(For example, higher systolic blood pressure and greater arterial stiffness)
Differences in body composition.
(Less total body water, more body fat, less lean muscle)
All of which can alter drug distribution, peak levels, and half-life.
In addition, older adults are more likely to be taking multiple routine medications, increasing the real-world risk of interactions between medications.
Older adults have less physiologic reserve to tolerate stressors, meaning that data from younger adults alone cannot reliably predict safety, dosing, and adverse-event patterns in older adults, particularly when the intended patient population is predominantly older.
A realistic evaluation of a drug’s effectiveness and adverse events requires that older and younger adults be represented and analyzed, with eligibility driven by health status and screening results rather than chronological age alone.