Recombinant DMA Advisoiy Committee - 3/S4/94 
Accelerated Review. In the event that a protocol is denied review by this accelerated 
process, the proposal will be reviewed by the full RAC. 
Dr. Smith said that the text on the proposed definition of the category on "umbrella" 
protocols need to be clarified. The category is not intended for a Principal Investigator 
to initiate a new study at multiple sites without a major review. Ms. Wilson explained 
that the definition applies to protocols in which the Principal Investigators indicated in 
their submission that the studies will be performed at multiple sites. Dr. Smith asked 
whether the initial review will be a Major Action. Dr. Parkman said that the initial 
review is a Major Action. Ms. Grossman asked whether the multicenter trial proposed by 
Vical, Inc., San Diego, California, that is based on a protocol previously approved for 
other Principal Investigators will be included in this category. Dr. Parlonan explained 
that this tri^ involves different study designs at many sites and is not a typical "umbrella" 
protocol. For reviewing an "umbrella" protocol, the master protocol will receive a major 
review and will be considered a Major Action when first submitted. When the Principal 
Investigator requests inclusion of additional sites, these modifications will be reviewed as 
a Minor Action. Ms. Grossman asked whether this category would include a protocol 
wherein a new Principal Investigator intends to perform a previously approved protocol 
at additional sites. Dr. Parkman said that if nothing substantially new is proposed, it 
could qualify as a Minor Action. Dr. Walters asked if the "umbrella" protocols differ 
from other categories involving new Principal Investigators and new sites. Dr. Parkman 
cited as a best example of the "umbrella" protocol would be the study of brain tumor 
treatment with herpes simplex virus thymidine kinase/Ganciclovir in which standard virus 
producer cells will be supplied ft’om a central laboratory for administration to patients at 
multiple sites. Dr. Parkman said that the "umbrella" category is new and that no 
protocols have been proposed for RAC review. Dr. Parkman noted that there is no big 
difference from other categories dealing with new sites and new Principal Investigators, 
but he envisioned that repeated submission of new protocol documents will not be 
needed in this "umbrella" category. 
Dr. Straus asked to clarify the definition of the Category 3 on new site/original Principal 
Investigator. Dr. DeLeon said that this category will be for a Principal Investigator to 
transfer a RAC-approved protocol to a new site. Dr. Zallen asked whether this request 
will be a minor modification. Dr. Wivel remarked that minor modification is also a 
Minor Action similar to Accelerated Review. Dr. Parkman explained that the reason to 
create this category for Accelerated Review is that transfer of a protocol to a new site 
sometimes will involve additional issues such as new laboratory expertise and new 
personnel. These new issues will be reviewed with a new protocol submission. Dr. 
Straus stated his understanding that Category 4, new site/new Principal Investigator, will 
be for a Principal Investigator who wishes to initiate a protocol previously approved by 
the RAC at a new site, and Category 3, new site/original Principal Investigator, will be 
for a Principal Investigator to take his or her own RAC-approved protocol to a new site. 
Dr. Post suggested that Dr. Parkman and the ORDA develop the final language to 
define these categories. Dr. Motulsky concurred. 
[58] 
Recombinant DNA Research, Volume 19 
