Ask the Experts: Exceptions to Informed Consent Requirements
This monthly feature presents a variety of questions from clinical trial professionals with answers from WCG Clinical’s expert staff. This month features Chief Medical Officer Lindsay McNair and Quality Assurance Adviser, Compliance, Yvonne Higgins.
Question: I am working with a study where a new informed consent form (ICF) has come out. We have subjects who are just waiting for a final phone call and no more on-site visits are required. Can we discuss the ICF changes with these subjects over the phone and answer any questions they have and then mail the ICF to them for signature and return?
Answer: Technically, there are no regulatory requirements that address the issue or process for “reconsenting” participants in an ongoing study. This obligation really stems from the required element of consent that states if there is new information that becomes available during the study that might affect participants’ decisions about whether to continue in the research, that information will be provided promptly.
When there is an update to informed consent information, the first question to consider is which of the study participants may need to know this information. If the change is related to screening procedures, then participants who are already on the study drug won’t reconsider study participation because of that change. A revision to the drug-dosing schedule won’t matter to participants who have completed dosing and are in the follow-up phase. New information that secondary cancers may be seen in people who receive this class of drug, even years later, would be important to future, current and past participants; if they’ve finished dosing, it can’t affect their decision about being in the study, but it may impact their future clinical care.
In this case, if participants are just waiting for a final follow-up call, do the changes to the consent information impact their participation or their future clinical care? If not, it may be reasonable to say that they don’t need to be reconsented at all. But if it does impact them, then the next question is the process.
FDA regulations allow a waiver of documentation of informed consent, which means that the consent process can be conducted verbally, and a note can be written to document that participants provided consent without giving their actual signature (56 CFR 109.1).
In your example, if it is appropriate to inform the participants in follow-up, it may be that obtaining verbal consent with documentation of that agreement in their research record is sufficient and it is not necessary for the ICF to be mailed and returned. It may even be better to rely on verbal consent, as some organizations are uncomfortable with obtaining signatures remotely because there is no way to tell who actually wrote the signature when it is unwitnessed.
Usually, the reviewing IRB will include directions for who needs to be reconsented when it approves the revised consent information, but not all IRBs do this. The sponsor can certainly suggest a plan for who should be reconsented and how reconsent will be obtained (e.g., signing the new written consent form for new participants and those on the study drug, and waiver of documentation of consent requested to allow verbal reconsent by phone for participants off the study drug but in long-term phone follow-up), which may be logistically feasible and less burdensome on both staff and participants. — Lindsay McNair, Chief Medical Officer, WCG Clinical
Question: We are developing oncology products, several of which will be targeted at a specific mutation/biomarker. We want to create a prescreening protocol to screen patients for this mutation and then just identify them with permission to recontact them when we have a study open for people with that mutation. Does the informed consent document have to include all the required elements of informed consent?
Answer: This is a common question as we see more therapeutics in development in which the patient population is identified based on a specific genetic mutation or biomarker and for studies of rare diseases. According to FDA guidance, the performance of laboratory tests and other screening tests for eligibility in a study is considered research: “Clinical screening procedures for research eligibility are considered part of the subject selection and recruitment process and, therefore, require IRB oversight,” the guidance says. Unless the procedure is being done as part of direct care or treatment, the FDA requires approval by the IRB of the prescreening activities and requires informed consent of the subjects prior to testing.
The IRB may approve a screening protocol and informed consent process separate from the consent process for a specific clinical study. The screening consent form must include a description of the tests, why the testing is needed and a brief summary of the study or type of studies in which the patient may later be asked to participate. In its guidance on waiver or alteration of informed consent for research involving no more than minimal risk, the FDA asserts that when the IRB determines that the screening tests pose no more than minimal risks to subjects, the IRB may allow changes to or omissions of the required elements of informed consent.
The FDA notes that physician-investigators need to take care to be sure that prospective participants in the study are informed that the tests are being performed solely to determine eligibility for the study. The informed consent process should also make clear to the prospective participant that, based on the test results, they may be excluded from participation in future clinical trials.
In those instances where the screening activities involve no more than minimal risk or involve procedures for which written consent is not normally required in the clinical care setting, the IRB may waive the requirement for the participant to sign the screening consent form. — Yvonne Higgins, Quality Assurance Adviser, Compliance, WCG Clinical