The new article highlights aspects related to the description of the software to be included in submissions associated with a medical device using it.


MHRA Guidance on Medical Software and Applications

The Food and Drug Administration (FDA or the Agency), the US regulating authority in the sphere of healthcare products, has published a guidance document dedicated to the concept of informed consent in the context of clinical investigations.

The document provides an overview of the applicable regulatory requirements, as well as additional clarifications and recommendations to be taken into consideration by study sponsors and other parties involved in clinical studies with human subjects involved.

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 existing legislation and has been agreed upon with the authority in advance. 

The scope of the guidance covers, inter alia, the aspects related to the basic elements of informed consent.

Alternative Procedures or Treatments

In accordance with the applicable legislation, namely, regulation 21 CFR 50.25(a)(4), informed consent should include a disclosure of appropriate alternative procedures or courses of treatment, if any, that might be advantageous to the subject. 

First of all, the authority emphasizes the importance of ensuring that potential study participants are able to make an informed decision on whether they should participate in a study. Accordingly, as highlighted in 21 CFR 50.25(a)(4), consent forms are required to disclose appropriate alternatives to joining the clinical investigation. 

Potential subjects should be informed of any suitable alternatives. This includes:

  • Approved therapies related to the patient’s disease or condition;
  • Other forms of therapy, like surgical interventions,
  • When applicable, supportive care without disease-directed therapy

Additionally, the disclosure must address the current medically recognized standard of care. This is especially important for investigations of medical products intended to treat or diagnose serious diseases. Sometimes, the standard of care may allow the use of a legally marketed drug or device, even if it falls outside the approved use for the product in question. When a consent form describes such an unapproved use, it must provide factual information without presenting it promotionally. For any concerns or ambiguities, the FDA expects the parties responsible for clinical investigations (sponsor) to provide the clarity necessary for potential participants to make informed decisions.

The dynamics of medical research mean that new alternative procedures or treatments can emerge during a study. In line with 21 CFR 50.25(a)(4) and 50.25(b)(5), it might be necessary to update consent discussions and documents to reflect these changes.

The FDA also emphasizes the importance of transparency when disclosing alternative treatments. This includes, inter alia, discussing foreseeable risks, potential benefits, and, when possible, quantified comparative estimates from clinical literature. Even if a written document does not contain an exhaustive risk/benefit analysis, the alternatives available should be discussed when obtaining informed consent. In certain situations, it might be beneficial to refer subjects to their primary care provider for a more comprehensive discussion about the alternatives, especially when these involve complex treatments. All such discussions should ideally conclude before the consent form is signed.

While an individual might qualify for multiple clinical investigations, the decision on the best fit is to be determined on a case-by-case basis. The authority also mentions that the subject’s involvement in one investigation could influence eligibility in others, so this aspect should also be taken into consideration. This sequence of participation and any implications are essential components of the informed consent conversation.

Confidentiality in the Context of Clinical Investigations

The scope of the guidance also covers aspects related to confidentiality. In particular, in accordance with regulation 21 CFR 50.25(a)(5), informed consent should contain a statement describing the extent, if any, to which confidentiality of records identifying the subject will be maintained and that notes the possibility that the Food and Drug Administration may inspect the records. 

Consent processes, based on the stipulations in 21 CFR 50.25(a)(5), must describe the scope of confidentiality for records identifying subjects. It’s vitally important for potential participants to be aware that various entities, including the study sponsor, research team, FDA, and others, might access these records. The FDA has the authority to inspect these records, and this possibility is something the consent process must duly communicate to potential study participants. Furthermore, it is important to mention that the FDA does not need explicit permission from subjects to access these records, even under the Health Insurance Portability and Accountability Act (HIPAA) Privacy Rule. In particular, the FDA may inspect study records to assess investigator compliance with the study protocol and the validity of the data reported by the sponsor.

As further explained in the guidance, the FDA might inspect and copy records connected to a clinical investigation for various reasons. While the FDA typically will not replicate records with the subject’s name unless this is reasonably necessary, there might be situations where such information becomes imperative, especially if there is a doubt about the authenticity of the records, their accuracy, and reliability. If the FDA needs to access personal health information, it generally treats such data as confidential. However, in rare, specific cases, disclosure to third parties is required, such as when mandated by a court of law. Thus, the consent process should not guarantee absolute confidentiality concerning records that might undergo FDA inspection.

In summary, the present FDA guidance highlights the aspects related to alternative treatment options in the context of clinical investigations and the informed consent associated thereto – the document explains the way such information should be communicated to potential study subjects. The document also addresses matters related to confidentiality and the approach to be applied when describing confidentiality-related aspects when obtaining informed consent.

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