45 CFR 46.111(a)(3) requires that the IRB ensure that researchers employ equitable selection methods when enrolling subjects.
45 CFR 111(a)
Criteria for IRB Approval
(3) Selection of subjects is equitable. In making this assessment the IRB should take into account the purposes of the research and the setting in which the research will be conducted and should be particularly cognizant of the special problems of research involving vulnerable populations, such as children, prisoners, pregnant women, mentally disabled persons, or economically or educationally disadvantaged persons.
Ensuring Fair Distribution
The requirement for equitable selection flows from the ethical principle of justice. Justice is intended in the sense of distributive justice where no group is unduly burdened or will unfairly benefit from the research. Originally this was interpreted as requiring protection of vulnerable groups but with the onset of the AIDS epidemic it became apparent that some groups did not have equal access to clinical trials. This led to a transformation where advocates for minorities, women and children have demanded equal access (and equal benefit) from clinical trials.
Equitable selection does not mean that all groups are represented in proportion to the population. It means that selection criteria should be both fair and appropriate to the research question. Research aimed at eliminating the risk of lead poisoning will by its very nature include more economically disadvantaged and minority subjects.
Subjects with Limited English Proficiency (LEP)
A commonly seen error is for the protocol and application to state that no subjects will be excluded from the study but to then fail to include a process that will permit individuals with limited english proficiency to enroll. It is important to determine prior to IRB submission whether or not it is appropriate and possible to enroll LEP individuals as subjects.
LEP individuals are potentially vulnerable because it may not be possible obtain a valid consent due to inability to fully comprehend the nature of the research and the risks and benefits of participation. The IRB may either conclude that it appropriate or inappropriate to include LEP individuals as subjects based on the circumstances.
When should studies include or exclude subjects with limited English proficiency?
Studies that offer a prospect for direct benefit, especially Phase 3 confirmatory trials targeting serious or life-threatening diseases, should generally make the greatest effort to enroll all eligible subjects. The fewer the treatment options and the greater the potential prospect for benefit, the more important it is to make the benefit of participation available to all.
It is easier to justify exclusion from early phase clinical trials where isn't strong evidence of efficacy, clinical trials that are greater than minimal risk without a prospect for direct benefit (e.g. many PK studies), and studies that are minimal risk but without any prospect for direct benefit.
It may not be possible for LEP individuals to participate when the study requires completion of surveys, questionnaires, tests, diaries, etc. that are not available in other languages. Some tests are not validated in any other language than English (or Spanish).
Summary: Common Justifications for Excluding LEP individuals from Participation
- Early phase clinical trials without a prospect for direct benefit, that will enroll only a limited number of subjects
- Studies without a prospect for direct benefit and with procedures that are greater than minimal risk;
- Assessment tools, surveys, questionnaires or psychological tests that are only available in English;
- Enrollment required in situations where translators will not be readily available (satellite clinics, after regular working hours, emergencies, etc.)
- Expectation based on experience that LEP individuals will rarely present to the clinic where enrollment will take place.
If LEP individuals are going to be included, consent be obtained and documented in one of two ways.
Translated Consent Form and an Interpreter
A translated version of the IRB-approved consent form that the subject can read can be used along with an interpreter who is fluent in English and the subject's native language. The interpreter must comply with the CHOP Language Services Policy. Translation of the consent document may be performed by a commercial service. The translator must be approved by the Hospital in accordance with the Language Services Policy. For more information see IRB SOP 701: Required Elements of Consent and Documentation of Consent.
Short Form Consent Form
The expense of translating consent forms using commercial services and the need to pay for translation of all modifications to the consent is an impediment to including LEP subjects. The short form consent process is a very cost-effective alternative to using translated consent forms. It is intended for situations where few LEP subjects are anticipated. See the IRB's webpage Short Form Consent for a detailed description of what is involved.
Philadelphia and Regional Census Data
45 CFR 46.111(a)(3) requires that the IRB determine that the research will ensure equitable selection of subjects. The census data from the city and region are useful for determining what the expected distribution of subjects should be for clinical research activities conducted at CHOP.
Examination of the census data from the greater Philadelphia region (below) shows that less than 10% of residents are foreign born. An even lower percentage are non-English speakers. In clinics that draw patients from specific regions the percentage could be much lower or much higher.