03 · What You Need to Know
Exclusion Criteria Need Reasons, Not Just Precedent
Eligibility criteria perform legitimate scientific and ethical work
Researchers need eligibility criteria to define the population being studied. Without boundaries, many research questions would become incoherent.
A study of adolescents requires an age range. Research on a particular disease requires evidence that participants have that disease. A trial may need to exclude people for whom an intervention creates unacceptable risk. A measurement study may require characteristics necessary for valid interpretation.
The problem is therefore not exclusion itself.
CIOMS states that unequal distribution of research burdens and benefits can be acceptable when scientifically and ethically justified, but inclusion and exclusion criteria should not rely on potentially discriminatory characteristics such as age or sex without sound scientific or ethical reasons.
Scientific relevance is one of the strongest justifications
An exclusion may be appropriate because the excluded population is outside the question the study is actually trying to answer.
Children do not need to be included in every study of Alzheimer's disease simply to demonstrate inclusivity. NIH explicitly identifies a condition not occurring in an excluded age group, or a research topic being irrelevant to that group, as potentially acceptable reasons for age-based exclusion.
Similarly, a study examining experiences during a first pregnancy does not need participants who have never been pregnant. A study of a particular professional practice can require experience in that profession.
Good eligibility criteria make the sample correspond to the scientific question.
Safety can justify exclusion when the risk is specific and defensible
Researchers have an obligation to minimize unreasonable risk. An intervention may present particular hazards for people with certain medical conditions, organ impairment, allergies, concurrent treatments, or physiological characteristics.
In those circumstances, exclusion may be ethically required rather than merely permissible.
NIH policy, for example, recognizes unacceptable risk to a particular age group as a potentially valid reason for age-based exclusion. Its guidance gives the example of excluding children from a high-risk Phase I study when the potential benefits do not outweigh those risks.
The important point is specificity. “Older adults may be complicated” is weaker than identifying the particular physiological or safety characteristic that creates the unacceptable risk.
Methodological validity can sometimes justify a restriction
Research procedures occasionally require a particular participant characteristic for the resulting measurement to mean what researchers claim it means.
A language-validation study may appropriately require proficiency in the language being validated. A visual-perception experiment may require a specified level of visual function. A pharmacokinetic study may initially require a narrowly defined population to isolate particular effects.
But methodological justification should not become shorthand for eliminating every source of real-world variation.
Watch Out
“A more homogeneous sample will be easier to analyze” is not automatically a sufficient ethical reason for exclusion. Researchers should distinguish characteristics necessary to answer the question from characteristics removed mainly to produce tidier data.
Legal and regulatory requirements can also justify exclusion
Some research populations are subject to specific legal or regulatory protections. A study may be unable to include a group because the proposed procedures do not satisfy those requirements.
NIH explicitly recognizes laws or regulations barring inclusion of a particular age group as a potentially acceptable basis for age-related exclusion.
Researchers should nevertheless identify the actual requirement rather than invoking “regulations” vaguely. A legal restriction, an institutional preference, and a research team's desire to avoid additional review are not the same thing.
A separate study can sometimes be better than forced inclusion
Some populations genuinely require a different research design.
Children may need age-appropriate outcomes, dosing, consent and assent procedures, or safety monitoring. Frail older adults may require different endpoints. A linguistic population may require a separately validated instrument. A disability may interact with the intervention strongly enough that simply adding a handful of participants would produce uninterpretable evidence.
NIH recognizes a separate age-specific study as a potentially acceptable justification for excluding an age group when such a design is warranted and preferable.
The crucial word is preferable. “We will study them separately” should represent a scientific rationale, not a polite way of postponing inclusion indefinitely.
Convenience becomes ethically weak when it substitutes for the real reason
Researchers work with limited money, time, staff, facilities, and recruitment networks. Feasibility matters.
But convenience can disguise itself as methodology.
Researchers may exclude older adults because follow-up is expected to be harder, non-English speakers because translation costs money, disabled people because facilities or instruments are inaccessible, or people with common comorbidities because they complicate analysis.
CIOMS states that participant groups should be selected for scientific reasons rather than because they are easier to recruit or manipulate and that unequal distributions should not be chosen arbitrarily or conveniently.
The same principle applies in reverse: people should not be excluded merely because including them is inconvenient.
Ask whether the criterion targets the real problem or merely a proxy
Suppose researchers exclude everyone over age 70 because they worry about renal impairment.
Age and renal function are related, but they are not identical. Some 72-year-olds may have adequate renal function while some 55-year-olds do not.
If renal function is what actually affects safety, a criterion based directly on renal function may be scientifically stronger and less exclusionary than an arbitrary age cutoff.
The same logic applies elsewhere. If the concern is cognitive capacity, assess capacity rather than assuming it from diagnosis or age where feasible. If the concern is medication interaction, identify the medication. If the concern is ability to perform a particular task, assess that ability rather than using disability status as a crude proxy.
Exclusion should be proportionate to the problem it solves
A criterion can have a legitimate purpose but still be broader than necessary.
Suppose a study intervention creates a known interaction with one class of medication. Excluding everyone with any chronic condition would solve the interaction problem, but at the cost of excluding many people who do not face that risk.
A narrower criterion may accomplish the same ethical purpose while preserving participation.
This suggests a useful principle: use the least exclusionary criterion that adequately protects scientific validity, participant welfare, and ethical requirements.
The relevance of the excluded population changes the ethical stakes
Excluding a group largely unrelated to the research question may have little ethical consequence. Excluding a substantial proportion of the people affected by the condition is different.
NIH's Inclusion Across the Lifespan policy is explicitly intended to help ensure that knowledge from NIH-supported research applies to populations affected by the diseases and conditions under study. NIH therefore requires inclusion across ages unless scientific or ethical reasons justify exclusion.
Likewise, the 2024 Declaration of Helsinki states that groups underrepresented in medical research should have appropriate access to participation.
When an exclusion would remove people central to the research problem, researchers should consider whether they are creating a sample that systematically excludes the people most affected by the question.
Protocol templates should not become ethical fossils
Eligibility criteria are often inherited. A previous study used an upper age limit, so the next protocol does too. A standard template says “English-speaking only.” A familiar clinical trial excludes pregnancy. Nobody remembers exactly why.
Historical precedent can be informative, but “we always exclude them” is not a scientific rationale.
Each study should reconsider whether inherited criteria remain relevant to its intervention, methods, population, evidence base, and current ethical standards.
