This monthly feature presents a variety of questions from clinical trial professionals with answers from WCG ‘s expert staff. This month features Christopher Doyle, director of IBC Services, Daniel Kavanagh, senior scientific adviser, gene therapy, and Yvonne Higgins, WCG IRB quality assurance adviser.

Question: How do emergency use authorizations (EUAs) for COVID-19 vaccines affect institutional biosafety committee (IBC) oversight requirements for ongoing clinical trials?

Answer: There are at least a dozen mRNA, DNA and virally vectored COVID-19 vaccines currently being tested in clinical trials. Given their composition, administration of such vaccines to research subjects constitutes human gene transfer under NIH guidelines for the protection of human subjects in research. That means IBC oversight is likely required at each individual trial site. Of note, the NIH guidelines apply to research, irrespective of a product’s FDA, EUA or approval status; if a subject is enrolled in a human gene transfer research trial, the fact that the gene transfer product has an EUA or is approved for use does not exempt that research from IBC oversight.

As EUAs for COVID-19 vaccines are issued, many sponsors are amending existing clinical trial protocols to allow previously blinded placebo recipients to receive an active vaccine. Importantly, subjects in these amended protocols are being vaccinated and followed as part of the clinical trial itself, rather than under the umbrella of an EUA outside of a clinical trial. Because of this, continued IBC oversight of such research is required. Sites should work with their IBCs to ensure compliance obligations are met, particularly as EUA issuance may lead to two groups of people receiving the same vaccine at the same site, but with differing oversight, biocontainment and safety requirements. — Christopher Doyle, director, IBC Services

Question: Does a human gene transfer (HGT) clinical trial require IBC approval at all sites?

Answer: Looking at this question from a sponsor perspective, points to consider include the following:

• Does the sponsor currently receive any direct NIH funding for research involving recombinant or synthetic DNA or RNA (for this or for other projects)? If so, all HGT research conducted by the sponsor company requires IBC approval at each domestic clinical trial site.
• Does the investigational product (IP) contain recombinant or synthetic DNA or RNA materials developed by the sponsor using current or past NIH funding? If so, any clinical research using this IP requires IBC approval at each domestic clinical trial site.
• Does the IP contain recombinant or synthetic DNA or RNA materials developed using NIH funds by some other business or institution, such as an academic research institution, and does that business or institution currently have contractual arrangements with the sponsor? If so, any clinical research involving those materials requires IBC approval at each domestic clinical trial site.

Looking at this question from a site perspective, points to consider include the following:

• Does my site belong to an institution or business that currently receives any direct NIH funding for research involving recombinant or synthetic DNA or RNA? If so, then all HGT clinical trials conducted at this site require IBC approval.
• Does a specific HGT clinical trial involve funding at the product or sponsor level as defined above? If so, then that specific clinical trial requires IBC approval.

— Daniel Kavanagh, senior scientific adviser, gene therapy

Question: Does the protocol for a trial involving genomic sequencing of deceased patients’ DNA need to specify that deceased patient DNA can be used? Who signs the consent form?

Answer: According to the federal regulations on human research protections (the Common Rule), a “human subject is a living individual about whom an investigator obtains data through an intervention or interaction or identifiable information.”

While research involving deceased individuals is not subject to the federal regulations on human research protections and therefore not under the regulatory purview of the IRB, other regulatory and ethical issues should be considered in the design and conduct of the research.

For example, the Health Insurance Portability and Accountability Act (HIPAA) applies to an individual’s protected health information (PHI) for 50 years after death. Uses and disclosures of PHI requires either authorization by family or a legally authorized executor of the individual’s estate or the researcher has to do the following:

• Document that use or disclosure of PHI is sought solely for research;
• Provide, at the request of the covered entity, evidence of death of the individual; and
• Provide representation that the use or disclosure of the PHI is necessary for the research purposes.

Many covered entities have delegated the oversight of HIPAA compliance to their IRBs. Be sure to check with the IRB or privacy board within your organization for guidance on how to adhere to their policies and procedures.

Some federal funding agencies, notably the NIH, have in place data-sharing policies that require informed consent for future research uses of data and specimens. Other ethical issues for consideration are how the analysis of DNA could be important clinically to the deceased patient’s next of kin. Careful consideration should be given to whether the family should be informed about ongoing research, whether the family members should give proxy consent for use of postmortem data and specimens, and if results should be shared with the family. — Yvonne Higgins, quality assurance adviser, compliance