RELEASE DATE:  January 28, 2004 

NOTICE:  NOT-RR-04-005

National Center for Research Resources (NCRR)

In 2002, three years after receiving retrovirally transduced stem 
cells, two subjects who were enrolled in a gene transfer research study 
developed T cell leukemia.  These events highlighted the potential for 
serious adverse events to emerge long after the subject’s active 
involvement in the study .  

Gene transfer research investigators must confront these risks in order 
to maximize the protection of human subjects who participate in gene 
transfer research protocols and to help advance understanding of the 
underlying mechanisms involved. 

To address these concerns, the FDA now recommends that all subjects 
enrolled in gene transfer studies be followed for 15 years after 
administration of the study agent.  FDA implements this recommendation 
by requiring gene transfer investigators to document their long-term 
follow-up plans in their IND applications.  FDA specifically expects 
investigators to perform annual physical examinations of each subject 
for the first five years after administration of the study agent and, 
for the subsequent ten years, to ask subjects to complete a 
questionnaire on health status changes.  Moreover, FDA expects 
investigators employing hematopoietic stem cells transduced by 
retroviral vectors to conduct certain laboratory studies semi-annually 
for five years and then annually for the following ten years to 
determine whether clonal cell populations have developed.  

Compliance with these recommendations is reasonably straightforward 
when the supporting grant is active. However, if the grant support 
ends, compliance becomes more challenging.  Nonetheless, grantees and 
their institutions must make every effort to ensure that follow up 
studies of gene transfer study participants are carried out and the 
data submitted to the FDA.  

To facilitate NIH grantee and institutional compliance with the FDA 
requirements, the National Center for Research Resources (NCRR) will 
support the cost of subject visits at a General Clinical Research 
Center (GCRG) located either at the institution to which the award was 
made or elsewhere.  The GCRC will provide clinical space, nursing, 
appointment scheduling, relevant routine laboratory tests, and 
phlebotomy.  The grantee institution will be responsible for providing 
support for subjects to travel to the GCRC.   

The resources of the GCRCs will not be freely available to 
investigators of industry-sponsored studies.  If GCRC resources are 
used in such instances, the institution will be responsible for 
obtaining reimbursement from the trial sponsor according to GCRC 
Guidelines http://www.ncrr.nih.gov/clinical/cr_gcrc.asp.

If blood samples need to be collected and stored, they may be drawn by 
the GCRCs and  stored at the National Gene Vector Laboratory (NGVL) 
repository at the Indiana University http://www.ngvl.org.  Storage 
services will be provided at no cost to NIH funded clinical gene 
transfer protocols.  Certain clonality tests may also be available at 
no cost to the investigators through the NGVL.

The data gathered during the 15-year follow-up period is to be 
submitted to the FDA.  There is no requirement for investigators to 
provide the data to the NIH funding institute unless the funding 
institute otherwise requires such data.  Investigators must, however, 
continue to comply with reporting requirements outlined in the NIH 
Guidelines for Research Involving Recombinant DNA Molecules. 

Principal investigators who receive NIH awards for clinical gene 
transfer studies should ensure that during the consent process 
participants are fully informed about the FDA requirements and the 
processes that are involved in conducting the long-term follow up 


Direct your questions about NCRR GCRC issues to:

Richard A. Knazek, M.D.
Division of Clinical Research Resources
National Center for Research Resources
Democracy One, Room 910
6701 Democracy Blvd.
Bethesda, Maryland 20892
Phone 301-435-0792
FAX 301-480-3661

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