13 
Dr. Walters asked the working group whether Section I-A-2-<i , Statistical 
considerations , adequately addresses statistical issues. 
Dr. Gorovitz questioned whether the section as written displayed a bias 
toward using several subjects. He asked if the working group would approve 
protocols involving a number of patients. Dr. Varmus felt the language of the 
section invites investigators to use many patients. Dr. Anderson said the 
first proposals reviewed by RAC would probably only have a single subject. 
Dr. Mot ul sky felt the only protocols involving more than one patient at this 
stage in human gene therapy would use siblings. He felt statistical consider- 
ations should be included in Sections I-A-2-a and I-A-2-b. 
Mr. Capron said Item I-A-2-d-(3) which deals with the qualifications of the 
investigator and the adequacy of laboratory and clinical facilities should not 
be part of statistical considerations. He suggested these considerations be 
placed in a separate section to emphasize their importance. He felt this 
approach was particularly important as the working group will not be making 
site visits. 
Dr. Walters asked the working group whether the language of Section I-B, 
Selection of Subjects , was adequate. Dr. Anderson said the first hunan gene 
therapy protocols probably will not have controls; the investigator will probably 
draw conclusions from comparisons with the natural history of the disease. 
Language referring to controls need not be included in Item I-B-l . 
Dr. Miller suggested this section of the working group document might request 
the criteria by which the diagnosis was reached. 
Dr. Grobstein felt the document should address the question of hew subjects are 
selected. He felt this section should be more thoroughly developed. 
Ms. Areen said this section mixes scientific design and ethical concepts. She 
wondered whether the clinical design section of the FDA manual (Attachment III) 
might be useful in constructing appropriate language for this section. 
Dr. Anderson said selecting subjects is a routine practice for clinicians and 
asked Drs. Murray and Mot ul sky whether they might attempt to construct language 
for this section. Drs. Murray and Motulsky agreed to develop language for 
Section I-B before the next meeting of the working group. 
Dr. Walters asked if this secrtion should address the issue of how the decision 
to treat will be made. Dr. Motulsky said this decision would be based on 
several different considerations. Dr. Goro/itz said the question is whether 
the working group wants the investigator to describe these considerations. 
Dr. Murray felt the proposal should list criteria used for including or excluding 
patients; he thought most investigators would choose to treat the sickest 
patients first. Dr. Grobstein suggested candidates for the first human gene 
therapy protocols may not be easy to find, and this would greatly influence the 
choice of patient. 
Dr. Gorovitz felt the working group document should request information on why 
a particular candidate was chosen. There is a great deal of interest in human 
[ 101 ] 
