ICH GCP E6 4.8.3 states that neither the investigator, nor the trial staff, should coerce or unduly influence a subject to participate in a trial, and special care must be taken to assure it is met when dealing with populations whose very nature places them in a situation where they might be more easily coerced or influenced.
For this reason, 45 CFR 46 outlines regulations pertaining to the additional protections required when working with vulnerable populations. Three specific classes of subjects are described here:
- Pregnant women, human fetuses, and neonates;
- Prisoners; and
Examining the regulations, how does this apply to the issue of consent versus assent for children in research?
In the United States, the legal age of consent can range from 18 to 21 years of age. According to 45 CFR 46.402 research subjects are considered children when they have not yet met the legal age for consent to procedures involved in the research trial under the law where the research is conducted. So, a multicenter trial that has a site in Mississippi (legal age 18) and a site in Alabama (legal age 19) can have differing requirements for consenting subjects. In this example, an 18 year old that enrolls in the trial at the site in Mississippi would be able to go through the consenting process themselves, while if they were to enroll at the site in Alabama they would need to assent and their parents would need to consent to participate.
Additionally, the regulation specifies that the IRB shall determine when children are capable of providing assent by taking into account their age, maturity, and psychological state for children who are approaching the legal age. This makes sense, given that one 17 year old might be much more adept at deciding whether or not they wish to participate in research than another based on these factors. Here is an example:
Child #1: 17 years old; borderline IQ; attends a special needs school
Child #2: 16 years old; attends a private college preparatory school and is class valedictorian
Most would agree that age alone should not be the deciding factor in whether or not they are capable of consenting to participate in a research trial, and one is probably much more able than the other. But how does one draw the line and make this determination? Better yet, how does a monitor verify that the correct decision is made? Best practice would be that when you are in doubt, ask the IRB. In fact, per the regulation, they have the ability to make this determination on a case by case basis if they wish. But even then, do all IRB’s have the expertise to consider a child’s age, maturity, and psychological state? Do they know the subject as well as the person performing the consenting process?
Not to complicate things further, but the regulation also specifies that when assent is required, consent can vary depending on the level of risk involved in the research. For research not involving greater than minimal risk as well as research involving greater than minimal risk (but presenting the prospect of direct benefit), the IRB can determine that it is permissible for only one parent to need to consent. While research involving greater than minimal risk (and no prospect of direct benefit), as well as research not otherwise approvable, requires the consent of both parents. So after you get over the first hurdle and determine whether or not assent is required, you then need to verify if one or both parents will need to sign consent based on risk. Let’s go to another example:
Study #1 involves an experimental medical device which previous research suggests may cure a life threatening illness from which the subject is suffering.
Study #2 involves a similar device that is not likely to cure them, but could provide knowledge to successfully treat others.
Which of the two studies requires both parents to consent? Which would it be permissible to obtain consent from only one parent? Again, when in doubt, consult your IRB. It’s also wise to err on the side of caution.
When situations that arise that fall into gray areas, it is also a good idea to document the considerations that took place when arriving at the final decision regarding assent.
We hope that this review will assist you in properly obtaining informed assent. We would love to hear about your experiences with the consenting process in vulnerable populations. Share your experiences below!
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