Note: Although this FDA-483 is an accurate representation of the original FDA-483 issued to the firm, it is not an exact copy. Slight modifications to the original FDA-483 have been made to accommodate its conversion to the HTML format. A scanned copy of the original FDA-483 is available in PDF format on this website.

1. Failure to prepare and maintain adequate documentation of minutes for fully convened IRB meetings in sufficient detail for six (6) out of 21 meetings, occurring on 1/9/00, 1/23/00, 2/13/00, 3/13/00, 3/27/00, and 4/10/00.

2. Failure to prepare and maintain adequate documentation of IRB minutes in sufficient detail to determine if an IRB member, who had a conflicting interest in a project, participated in the initial review or voting for his project. For example, RPN #00-11-07-02 was approved by the fully convened IRB on 12/12/00. A co-investigator in that study, who was also an IRB member, was documented as being present at this meeting. There was no indication that this member did not participate in the initial review or voting.

3. Failure to follow written procedures for conducting the initial review of research. IRB guideline "IV. A. Full Board/Committee Review," provides that the protocol application packet, including the proposed consent document, will be distributed to all IRB members for review and comment. The procedure then requires that "significant issues, comments or questions" regarding the protocols be sent to the subcommittee and then forwarded to the investigator in writing for a response, prior to the fully convened IRB meeting. Some, but not all, comments or questions were forwarded to the investigator. For example:

A. Study RPN #00-11-07-02

(1) One (1) IRB member questioned in writing about the "sample size reasoning/calculation." This same IRB member commented in writing about including children in the study given the low risk of [redacted]. There was no documentation to show that these concerns were sent to the clinical investigator in writing for a response.

B. Study RPN #99-03-19-07

(1) One (1) IRB member questioned in writing, "why start this study before the results of GOG [Gynecologic Oncology Group] #157 [another trial using different cycles of the study drug] are known?" There was no documentation to show that this concern was sent to the clinical investigator in writing for a response.

4. Failure to review research at fully convened IRB meetings at which a majority of IRB members are present, in that reviews are conducted by individual IRB members and/or in subcommittees at which only a minority of the IRB membership is present. Multiple studies, approved by the subcommittee, are approved by block vote at fully convened meetings of the IRB. The meeting minutes do not always document that the IRB discussed, considered, or determined whether the various issues, comments and questions raised by individual members were addressed or resolved. For example,

A. Study RPN #00-11-07-02

(1) On 11/10/00, one (1) IRB member documented that the "language could be simplified in the risk section." At the final subcommittee meeting on 12/11/00, the Pharmacy and Therapeutics Committee (P&TC) member documented that although the proposed consent document was changed, it was still too technical and not in lay terms, especially regarding risks. When the IRB convened on 12/12/00, it approved 26 protocols by a single block vote, but only (3) of these protocols were discussed. The P&TC member was not present, this protocol was not discussed, and there was no documentation in the written minutes or in the audio tapes to show that this issue was resolved.

5. Failure to require that information given to subjects as part of the informed consent minimizes the
possibility of undue influence. The consent document emphasized the expensive nature of test articles provided to the subject(s) at no cost. For example: (On the original document, the words in italics were hand-written and the initials of the investigators and Dr. Dang were at the end of the sentence.)

On 4/14/98, the fully convened IRB reviewed and approved the consent form for RPN# 97-02-03-04. The consent form provided under "Benefits" that "you will receive treatment with an [redacted] which will be provided at no cost to you or your insurer (standard cost $[redacted] ) or [redacted], which is also expensive."

EMPLOYEE(S) NAME AND TITLE (Print or Type)
J. Diann Shaffer, Investigator
Gerald W. Miller, Compliance Officer