Table of Contents
The document provides an overview of the applicable regulatory requirements, as well as additional recommendations to be taken into consideration by medical device manufacturers, study sponsors, and other parties involved in clinical investigations in order to ensure compliance thereto. At the same time, it is important to mention that provisions of the guidance are non-binding in their legal nature, nor are they intended to introduce new rules or impose new obligations. Moreover, the authority explicitly states that an alternative approach could be applied, provided such an approach is in line with the respective legislation and has been agreed with the authority in advance.
The document describes in detail the most important elements of informed consent and highlights the key points to be considered in this respect. In particular, the applicable regulations identify six additional elements to be communicated to potential study participants where necessary (when the appropriate information is material for them to make an informed decision).
Unforeseeable Risks
In accordance with the applicable regulation, namely, 21 CFR 50.25(b)(1), informed consent should contain a statement that the particular treatment or procedure may involve risks to the subject (or to the embryo or fetus, if the subject is or may become pregnant) which are currently unforeseeable.
As explained by the FDA, the consent process should explicitly address any potential risks that are not foreseeable before the commencement of the clinical investigation. This is especially important if long-term safety studies, such as teratogenicity studies, have not yet been completed. Subjects should be duly informed of these gaps in knowledge, including specialized considerations if the subject is or may become pregnant. Sponsors are encouraged to outline whether birth control measures should be taken and whether the occurrence of a pregnancy needs to be reported to the investigator, as part of the study protocol and consent document.
Verification, Validation, and Installation
The document emphasizes the importance of verification and validation activities to be performed each time maintenance modifications take place. In particular, the authority recommends carrying out full system regression testing due to the complexities and unknown logic paths introduced by new OTS software components. Detailed test reports should provide objective evidence that all identified hazards, both at the system and component levels, have been adequately addressed in order to ensure the safety of patients.
According to the document, changes in OTS software components could affect installation requirements. These changes could range from minor adjustments in documentation to significant upgrades. As explained by the FDA, the submission should clarify the impact of these new or modified OTS components on devices that are already in use.
Involuntary Termination of Subject’s Participation
The aforementioned regulation also requires informed consent to address anticipated circumstances under which the subject’s participation may be terminated by the investigator without regard to the subject’s consent.
According to the document, the informed consent process should also disclose the circumstances under which a subject’s participation might be terminated involuntarily by the investigator. This could occur if a subject fails to comply with the investigation protocols, such as missing scheduled clinic visits or not following the dosage or device instructions.
A generalized statement about potential withdrawal by the investigator is deemed inadequate by the FDA – all such cases should be clearly described. The authority additionally emphasizes the importance of ensuring that subjects are informed about the specific circumstances that could lead to their involuntary termination from the study, as well as how their already collected data will be managed.
Additional Costs to Subject
When it comes to costs, informed consent should provide information about any additional costs to the subject that may result from participation in the research.
Transparency regarding any additional costs that may be incurred by the subject during the investigation is mandatory. Subjects should be well-informed about any out-of-pocket expenses, such as insurance deductibles or copayments, and whether funds are available to cover these additional costs. The FDA recommends that, due to the complexity of this issue, subjects may need to consult with financial advisors to fully understand the cost implications.
Consequences of Subject’s Decision to Withdraw
As it was mentioned before, study participants are allowed to cease their participation at any time without facing any negative consequences. Thus, informed consent should clearly outline the consequences of a subject’s decision to withdraw from the research and procedures for orderly termination of participation by the subject.
The document emphasizes that the informed consent process should not only discuss the conditions under which a subject can withdraw but also the consequences of such an action. This includes, inter alia, outlining the recommended withdrawal procedures to ensure the subject’s safety. According to the FDA, subjects must be fully informed about the possible adverse effects of prematurely terminating the investigational intervention. They should also be made aware of the time commitment needed for the study, allowing them to evaluate their ability to complete it.
Providing Significant New Findings to Subjects
The applicable regulation also requires the study sponsor to ensure informed consent includes a statement that significant new findings developed during the course of the research which may relate to the subject’s willingness to continue participation will be provided to the subject.
According to the guidance, the consent form should include a provision that subjects will be updated with any significant new findings that may influence their willingness to continue with the study. The FDA suggests that this is vitally important, especially in clinical investigations involving first-time use of an investigational product, novel therapies, or where there is significant risk involved. If such new findings emerge, the Institutional Review Board (IRB) should consider re-engaging with the enrolled subjects to reassess their willingness to continue participation.
Number of Subjects
The authority also mentions that potential study participants should be informed about the approximate number of subjects involved, as in certain cases this could impact their decision to participate.
In summary, the document provides a detailed guideline on the key considerations that need to be addressed during the informed consent process in clinical investigations. The framework described in the guidance is intended to ensure that subjects are adequately informed and protected, and have all the information they reasonably need to make an informed decision.
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