Waiver requirements differ depending on whether or not FDA regulates the research. Also, there are different requirements for waiving (or altering) informed consent overall, versus waiving the requirement to document written informed consent.
So, when applying for a consent waiver, determine first: is the research FDA regulated, and is an overall waiver, or just a waiver of getting written consent, what is required?
Please note that any waivers or alteration of consent, or its documentation, are, in the end, the IRB’s decision, not the investigator’s or the sponsor’s. Aspire will work with its clients to be sure that the decisions and their documentation are appropriate.
Most of the research submitted to Aspire is FDA-regulated, so let’s start there.
For waivers of informed consent overall, in FDA-regulated research: FDA allows full-on waivers of informed consent only in limited situations. A long list of requirements must be met, but the “gatekeeper” requirement is that the research must be emergency research for life-threatening situations. See 21 CFR 50.24 for the applicable regulations. If your research is FDA-regulated (that is, involving a drug, device, or other substance regulated by FDA), and it is not emergency research, you need to get informed consent, and follow the required elements of informed consent.
A significant exception to this is in vitro diagnostic device research that uses archived, leftover human specimens obtained during the course of other research or routine clinical care. The regulations do not say that consent may be waived in such cases, but, in a 2006 guidance document, the FDA said it would use its “enforcement discretion” if seven specific criteria are met and the IRB documents that they are met. The criteria, paraphrased here, are IRB review of the study, plus these six: a) the device must be IDE-exempt; b) the specimens must be leftover from routine care, analysis, or other research, and would have otherwise been discarded; c) the specimens are not individually identifiable by the investigators “or any other individuals associated with the investigation or the sponsor”; d) clinical information may accompany the specimens as long as it does not make the specimen source identifiable; e) the individuals caring for the patients supplying the specimens “are different from and do not share information about the patient with those conducting the investigation”; and f) the specimens are provided “without identifiers and the supplier of the specimens has established policies and procedures to prevent the release of personal information” (emphasis by Aspire). ALL of these must be met. The last one, item f) bears particular emphasis: there must be a process in place at the specimen source (e.g., tissue bank) to protect personal information, and the IRB must be satisfied that the process is in place.
Also, for research involving children (minors), FDA regulations provide, in 21 CFR 50.55, for waiver of assent under certain conditions: a) the child is unable to provide assent, OR b) (paraphrasing here) the prospect of direct benefit is important and available only in the study, OR c) the research is minimal risk AND the waiver will not harm the children’s rights or welfare AND the study could not be “practicably” carried out without the waiver AND “whenever appropriate,” the subjects will be given pertinent information after participation in the study is over. These criteria also apply to alteration of the assent process.
[Note that “practicably”: Many have complained about the use of that word. Interpreting it in the context of the regs involves a judgment call by the IRB.]
FDA does allow that the requirement to document informed consent may be waived (21 CFR 59.109) if EITHER the research is emergency research, OR “the research presents no more than minimal risk of harm to subjects and involves no procedures for which written consent is normally required outside of the research context.” At least, these are easier to remember, but if they apply, informed consent still must be obtained—you just don’t need an ICF. In this case, the IRB will decide whether the exemption applies to all subjects in the study, or just some, and the IRB may require the investigator to provide subjects with a written statement about the research.
For research not regulated by FDA, the OHRP regulations in 45 CFR 46 are the most applicable. In general, these apply to federally-funded research, but under the rubric of the Common Rule, Aspire considers them to apply to non-FDA-regulated human subject research in general when it comes to questions of waiving consent. Here:
The requirement to obtain informed consent may be waived, or the elements altered, for non-FDA-regulated research, if ALL of the following are true (45 CFR 46.116(d)): the research involves no more than minimal risk to subjects AND the waiver or alteration will not adversely affect the subjects’ rights or welfare AND the research could not be “practicably” [there’s that word again] carried out without the waiver or alteration AND subjects will be given pertinent information after participation “whenever appropriate.” Sound familiar? Note this overlaps with FDA’s requirements ONLY with regard to waiver of assent for children.
Finally, the requirement to document informed consent may be waived for non-FDA-regulated research (45 CFR 46.117(c)) if EITHER “the research presents no more than minimal risk of harm to subjects and involves no procedures for which written consent is normally required outside of the research context” [consonant with FDA on this point] OR the consent form would be the only record linking the subject and the research, and the principal risk would be harm from a breach of confidentiality. Note that, in the latter case, “each subject will be asked (emphasis ours) whether the subject wants” such documentation, “and the subjects (sic) wishes will govern.”
It’s not TOO complicated, but it can get confused. When requesting a waiver of some sorts regarding consent, walk through this process. Ask Aspire for help if you need.
Oh, and note: the above doesn’t have anything to do with HIPAA waivers. That’s a different topic, for another time.
