Attachment IV - Page 21 
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9. In section I.B.2.C. (1 Hd' on p. 2943, we believe that the phrase 
"specifically germline cells" should he deleted because apprehension about 
an effect on gametes should be.no greater than for other tissues 
including, for example, blood or bone cell precursors. A clearer way of 
asking the question might be, "What is the specificity of transformation 
or other effects on the target cells?" 
10. In section I.B.2.C. (1 He! on p. 2943, we believe that the first sentence 
would be clearer if revised to read, "Describe animal experiments 
completed or in progress employ' ng protocols similar to that proposed." 
11. In section I.B.2.c.(2) on p. 2943, we suggest that an additional question 
be included, "How long have animals - especially those in which the 
desired gene is retained and/or expressed - been followed after treatment?" 
12. In section I.B.3., on p. 2943, we believe that the criteria for "selection 
of subjects" should be included here, rather than as a separate section 
I.C. 
13. In section I.B.3.e. on p. 2943, we suggest that the first sentence of the 
section is sufficient. The remainder requires of the investigator 
extremely complex speculation and should be deleted. 
14. In section I.D.: The initial paragraph under "informed consent" would 
provide sufficient guidance, without points 1-5, if the following were 
added to the paragraph: 
"The consent form must adhere to the requirements of 45 CFR 46 and 21 
CFR 50. Special attention must be paid to the applicability of the 
additional elements of informed consent listed in these regulations. 
(Include a copy of the patient consent form as part of the 
documentation requested in Part III, below.)" 
Points 1-5 are a partial listing of the elements of informed consent and 
may be misleading to applicants. If such a listing in detail is 
determined to be necessary, we believe it should include al 1 of the basic 
and additional elements of informed consent contained in the 
regul ations. 
15. In section I.E. on p. 2944, the initial paragraph under "Privacy and 
Confidentiality" would, we believe, provide sufficient information, 
without points 1 and 2. 
16. In section II on p. 2944, we believe strongly that only point A should be 
retained. The others are, we believe, not appropriate to this document or 
are duplicative. The inclusion of the other points would reflect 
incomplete understanding of the concepts discussed in point #19, below. 
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