Effective April 27, 2016, the NIH Guidelines for Research Involving Recombinant or Synthetic Nucleic Acid Molecules (NIH Guidelines) has been revised to update the procedures for review of human gene transfer trials. A version of the April 2016 NIH Guidelines can now be found at https://osp.od.nih.gov/biotechnology/nih-guidelines/.
Summary of Changes to the NIH Guidelines:
- IBC Review of Informed Consent Forms: The IBC is no longer responsible for review of several elements previously required by the Guidelines. These elements that are no longer reviewed by the IBC are reproductive concerns, request for autopsy, and interests of the media. However, the IBC will continue to review the Informed Consent Documents to ensure that the following items are covered: long-term follow-up; declaration that the study agent is genetically modified and how the modification is introduced; the risk of any transgene expression that may occur as a result; the risk of interactions between personal health issues and the study agent (e.g., rescue of replication-defective AAV via co-infection with Herpes virus or Adenovirus).
- NIH Recombinant DNA Advisory Committee (RAC) Review: RAC review of individual human gene transfer protocols will be performed only in exceptional cases that meet the following specified criteria (criteria listed in both items 1 and 2 must be met):
- An oversight body (e.g., IBC or IRB) determines that a human gene transfer protocol would significantly benefit from RAC review; and
- One or more of the criteria below are satisfied:
- The protocol uses a new vector, genetic material, or delivery methodology that represents a first-in-human experience, thus presenting an unknown risk.
- The protocol relies on preclinical safety data that were obtained using a new preclinical model system of unknown and unconfirmed value.
- The proposed vector, gene construct, or method of delivery is associated with possible toxicities that are not widely known and that may render it difficult for oversight bodies to evaluate the protocol rigorously.
- Registration with the NIH: Registration with the NIH will still be required for all human gene transfer studies. However, several changes to this process are being implemented. The Principal Investigator will remain responsible for submitting documentation regarding a proposed human gene transfer protocol to local oversight bodies and to the NIH, but documentation submitted to the NIH shall also include written assessments originating from all oversight bodies involved in the review at an initial site(s) as to whether RAC review is warranted. Also, the NIH is reducing the document submission requirements as outlined in Appendix M-I-A.
- NIH Registration Exemption for Vaccine Trials: Certain types of vaccine trials are exempt from NIH registration and subsequent reporting; however, IBC approval is still required. Specifically, this NIH registration exemption applies to clinical studies involving the administration of recombinant or synthetic nucleic acid molecules in which:
- induction or enhancement of an immune response to a vector-encoded microbial immunogen is the major goal,
- such an immune response has been demonstrated in model systems, and
- the persistence of the vector-encoded immunogen is not expected.
How Does This Impact Human Gene Transfer Research at UCLA?
- A new question has been added to the Human Gene Transfer page in SafetyNet. This question will ask the PI to evaluate whether the study should or should not be submitted to NIH RAC for review based on the new criteria. The IBC will then review this information and confirm that RAC review is or is not necessary.
- Attaching the RAC Application and RAC Review Letter are no longer required for IBC submission, unless it has been determined that RAC review is necessary. These questions are now optional in the Human Gene Transfer page in SafetyNet.
- Because the NIH registration process requires a written assessment from the IBC, the IBC review will need to take place prior to registration with NIH. The PI will then need to submit documentation to the IBC that the study has been registered with NIH prior to the final IBC approval letter being issued.
- You may not need to register your recombinant DNA vaccine trial with NIH; however, IBC approval is still required.
- With the exception of exempt vaccine trials, submission of follow-up data is not impacted by these changes. For all studies, Serious Adverse Events and Annual Reports still need to be submitted to the IBC. For all studies registered with the NIH, all Serious Adverse Events and Annual Reports still need to be submitted to the NIH.
- Webinar: WCG will be holding a webinar titled “RAC Changes from NIH: What Will They Mean to You?” on Wednesday, May 11, 2016 at 12PM. This is a great opportunity to learn more about the revised process. You may register for this webinar at http://go.wcgclinical.com/e/69962/starthere-jsp-ei-1101603/48npfp/184354108
- RAC Revisions Fact Sheet
- FAQs on the NIH Review Process for Human Gene Transfer Trials (April 2016)
- FAQs on the NIH Guidelines Vaccine Exemption (April 2016)
Please let us know if you have any questions.