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Federal Register / Vol. 57, No. 2 / Friday, January 3, 1992 / Notices 
cancer vaccine in the patient consent 
form. 
VI. Amendment to Appendix D-XV of 
the NIH Guidelines Regarding a Human 
Gene Therapy Protocol/Drs. Blaese and 
Anderson 
In a letter dated December 20, 1991, 
Drs. R. Michael Blaese and W. French 
Anderson of the National Institutes of 
Health, Bethesda, Maryland, requested 
an action item concerning a major 
amendment to the protocol entitled, 
"Treatment of Severe Combined 
Immunodeficiency Disease (SCID) due 
to Adenosine Deaminase (ADA) 
Deficiency with Autologous 
Lymphocytes Transduced with a Human 
ADA Gene." 
This protocol was originally approved 
by the Recombinant DNA Advisory 
Committee at its meeting on July 31. 
1990. and approved by the Director, NIH 
(September 12, 1990, 55 FR 37565). 
The requested amendment would use 
as a supplemental therapy CD-34 + cells 
(the peripheral blood stem cell fraction) 
transduced with the gene coding for 
adenosine deaminase. 
VII. Amending Section IV-B and Adding 
Sections IV-C and IV-*D to the Points to 
Consider in the Design and Submission 
of Protocols for the Transfer of 
Recombinant DNA into the Genome of 
Human Subjects Regarding Reporting 
Requirements for Human Gene 
Transfer/Gene Therapy Protocols 
At the Human Gene Therapy 
Subcommittee meeting on July 30-31. 
1991. the subcommittee formed a 
Working Group on Data Management. 
The working group was charged with 
developing a system for analyzing 
approved protocol results for the 
purpose of ensuring quality control in 
the approval process and to devise a 
follow-up procedure for analyzing 
already approved protocols. During the 
Human Gene Therapy Subcommittee 
meeting on November 21-22, 1991, a 
proposed reporting document was 
developed by the working group and 
submitted for review that would become 
Sections IV-C and IV-D of the Points to 
Consider. 
Sections IV-C and IV-D of the Points 
to Consider will be an expansion of the 
Reporting Requirement section. It 
includes the requirements for the 
investigators to provide a detailed 
follow-up of approved human gene 
therapy /gene transfer protocols. 
The Human Gene Therapy 
Subcommittee suggested minor changes 
to this section. The Recombinant DNA 
Advisory Committee will receive the 
following modified version of this 
proposed section from the Human Gene 
Therapy Subcommittee at the meeting of 
February 10-11, 1992. Section IV, 
Reporting Requirements, of the Points to 
Consider will be amended in Section 
IV-B. and two new sections. IV-C and 
IV-D, will be added. 
Section IV-B of the Points to Consider 
currently reads: 
“Section IV-B. Reports regarding the 
general progress of patients should be 
filed with both your local IRB and 
ORDA within 6 months of the 
commencement of the experiment and at 
six-month intervals thereafter. These 
twice yearly reports should continue for 
a sufficient period of time to allow 
observation of all major effects. In the 
event of a patient’s death, a summary of 
the special post mortem studies and 
statement of the cause of death should 
be submitted to die IRB and ORDA, if 
available.” 
Reporting requirements will be more 
clearly defined in the new Sections IV-C 
and IV-D of the Points to Consider 
below. Therefore, Section IV-B will now 
read: 
“Section IV-B. Reports regarding the 
general progress of patients should be 
filed with both your local IRB and 
ORDA. ORDA requests the first report 
after one year of the commencement of 
the experiment (See Section IV-C). and 
at yearly intervals thereafter (See 
Sections IV-D). These reports should 
continue for a sufficient period of time 
to allow observation of all major effects. 
In the event of a patient’s death, a 
summary of the special post mortem 
studies and statement of the cause of 
death should be submitted to the IRB 
and ORDA. if available." 
Two new sections, IV-C and IV-D 
will be added to the Points to Consider. 
The proposed sections read as follows: 
"Section IV-C. Reporting Form "A". 
This information is being collected from 
each gene transfer protocol approved by 
the RAC that involves human subjects. 
The information on this form will be 
requested only with the first report. 
“Section IV-C-1. General Information. 
“Section IV-C-l-a. Indicate the: (1) 
Name of principal investigator, (ii) name 
of study, and (iii) date of report. 
‘Section IV-C-l-b. What is the 
current status of the study (i.e., is it open 
or closed)? If closed, include: (i) Date 
protocol closed; (ii) describe reason for 
closure; and (iii) submit summary. 
“Section IV-C-2. Approval Process of 
Protocol. 
“Section IV-C-2-a. Supply a copy of 
the latest version of the protocol 
including copies of sample case report 
forms or any other data collection forms 
that are being employed as part of this 
study. 
"Section IV-C-2-b. Indicate the dates 
of the following approvals: Institutional 
Review Board, Institutional Biosafety 
Committee, Human Gene Therapy 
Subcommittee, Recombinant DNA 
Advisory Committee, and Food and 
Drug Administration. 
"Section IV-C-2-b-(l). Note major 
changes suggested by each committee 
and the responses to those suggestions. 
“Section IV-C-2-c. Have there been 
any amendments to the protocol? 
“Section IV-C-2-d. Describe your 
proposed standard quality control 
measures. 
“Section IV-D. Reporting Form "B". 
An annual update of the following 
information will be required. Each 
question may not be applicable to each 
protocol. 
“Section IV-D-1. General Information. 
“Section IV-D-l-a. Indicate the: (i) 
Name of principal investigator, (ii) name 
of study, and (iii) date of report. 
"Section IV-D-l-b. What is the 
current status of the study (i.e., is it open 
or closed)? If closed, include: (i) Date 
protocol closed: (ii) describe reason for 
closure; and (iii) submit summary. 
“Section IV-D-l-c. Have there been 
any amendments to the protocol? If so. 
indicate the dates of the following 
approvals: Institutional Review Board 
(IRB) and Office of Recombinant DNA 
Activities (ORDA). 
“Section IV-D-l-d. Have there been 
any adverse reactions reported? If so, 
describe. What dates were they reported 
to the IRB and ORDA? 
“Section IV-D-2. Measurements of 
Gene Transfer Success In Vitro. 
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"Section IV-D-2-a. Describe what you S 
are doing currently and how this 
compares with what you proposed. 
"Section IV-D-2-b. What material are 
you administering to the patients via 
what route? is this different from what 
you proposed? 
“Section IV-D-2-c. What in vitro 
evidence is there for the efficacy of the 
genetic manipulation prior to 
administration of the material, i.e., the 
efficiency of gene transfer and the 
manufacture of the desired product? 
How do your results compare with 
anticipated results? 
"Section IV-D-2-d. Have there been 
any unexpected results of the ongoing 
quality control measures? In particular, 
has there been any incidence of 
replication competent virus or vector 
rearrangement? Are these tests 
performed for each lot of materials , 
administered? 
“Section IV-D-2-e. Are there 
problems that have occurred that you 
did not anticipate prior to starting the 
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Recombinant DNA Research, Volume 15 ! 
