Recombinant DNA Advisory Committee - 6/9-10/94 
Informed Consent regarding revision of Part I-D, Informed Consent, of the Points to 
Consider. At the December 2-3, 1993, RAC meeting. Dr. Gary Ellis, Director of the 
NIH Office for Protection from Research Risks (OPRR), suggested that many of the 
RACs concerns regarding informed consent could be addressed by amending the Points 
to Consider. At the March 3-4, 1994, RAC meeting, the working group presented two 
draft versions of revised Part I-D of the Points to Consider for RAC consideration. 
Following a lengthy discussion, the RAC recommended that elements of the two draft 
documents should be incorporated into a single document for review and approval by the 
RAC. Following a working group telephone conference, a revised document was 
developed. 
Part I-D-1 of the revised document requests information regarding the informed consent 
process. Part I-D-2 describes issues that should be addressed in the Informed Consent 
document. Part I-D-2-a describes general requirements for research involving human 
subjects. Part I-D-2-b describes special requirements specific to gene transfer research, 
i.e., use of barrier contraception, long-term follow-up, request for autopsy, and protection 
from the media. 
Dr. Motulsky commented on Part I-D-2-a-(5) which includes verbal descriptions of 
quantitative information relating to risk. The proposed language is inconsistent with the 
common usage of the terms rare, uncommon, common, and frequent. The proposed 
document defines rare as < 0.1%; uncommon as < 1%; common as 1 to 10%; and 
frequent as > 10%. Dr. Motulsky explained that the more common usage of these terms 
is as follows: rare as < 0,5%; uncommon as 0.5 to 2%; occasional as 2 to 15%; common 
as 15 to 35%, frequent as > 35%. Dr. Parkman expressed concern about assigning 
numerical values to verbal descriptors since most risks, i.e., adverse events, caimot be 
precisely quantitated due to the extremely small number of patients who have been 
entered onto gene transfer trials to date. Ms. Buc said that the use of verbal descriptors 
is acceptable if used to disclose the investigators' quantitative estimate of risks. Dr. 
Smith agreed with Dr. Motulsky's quantitative definition. Dr. Chase said that 
quantitative information can be determined from an appropriate probability model; 
therefore, the verbal descriptors are acceptable as defined. Dr. Walters asked the RAC 
whether the proposed terms should be associated with a numerical value. Drs. Smith 
and Miller emphasized that quantitative definition are preferable. Ms. Buc said that 
investigators retain the option not to include these terms in their Informed Consent 
documents. 
Dr. Zallen said that Ms. Lori Andrews (a RAC member who was not present) suggested 
revision of the autopsy section to indicate that permission for autopsy will be requested 
but it is not a requirement. 
Regarding Part I-D-2-b-(l) on barrier contraception, Ms. Buc said that it is inappropriate 
to exclude pregnant women from participation in gene transfer studies since it assumes 
that a woman's right is subservient to that of the fetus. Dr. Zallen said that this 
exclusion is to protect the gene therapy research from being associated with any 
untoward effect such as a malformed newborn even if it is not directly due to gene 
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Recombinant DNA Research, Volume 19 
