David G. Greenhalgh, M.D., Chief of Burns, Shriners Hospitals for Children Northern California, Sacramento, CA, March 6

Warning Letter Bulletin, April, 2006

CDRH informed Greenhalgh of objectionable conditions observed during an FDA inspection conducted at his clinical site from Sept. 2-Oct. 27, 2005. The purpose of the inspection was to determine whether Greenhalgh's activities and procedures related to participation in the clinical study of an unamed radiological device were om compliance.

The audit revealed several serious violations regarding IDEs and the protection of human subjects.

Deviations included failure to ensure the investigation was conducted in accordance with the signed agreement with the sponsor, the investigational plan and applicable FDA regulations.

According to the warning letter, Greenhalgh revised or removed sections of the protocol prior to obtaining approval from the sponsor.

For example, in his protocol dated March 31, 2000, Greenhalgh added a site selection and randomization schedule under the heading "Design," which was designed to compare two sites of similar area and depth for each test. This design addition was not in the sponsor's original protocol nor did Greenhalgh receive approval for this change, CDRH noted.

Moreover, Greenhalgh changed the amount of irrigation solution on June 22, 2000, from that specified in the sponsor's protocol dated Nov. 1, 1999. This change would affect wound chemistry and possibly healing, FDA emphasized.

Additionally, although the sponsor's original protocol required endpoint data to be collected, Greenhalgh did not do so, claiming that he did not receive the instruments to perform the biophysical measurement tests and thus believed he was under no expectations to perform the tests.

Conversely, CDRH noted, this data requirement was included in the original sponsor protocol and deleted from the eight subsequent protocols that were revised independently by Greenhalgh without discussion with the sponsor.

In Greenhalgh's Nov. 7, 2005, response letter, he claimed that the sponsor never informed him that he needed to complete protocol deviation report; he also claimed to have orally discussed the protocol changes with the sponsor.

Additionally, CDRH said Greenhalgh failed to maintain accurate, complete and current records regarding the receipt, use or disposition of the study device.

FDA investigators noted that device accountability logs were not maintained, and devices were stored in an unsecured area where employees not part of the study had access to them.

Lastly, the agency pointed out that Greenhalgh had neglected to maintain each subject's case history and exposure to the device, including all relevant observations.

For example required photographs of patient exposure to the device were not taken within the protocol timeframes for three subjects, and Greenhalgh eliminated the requirement of post-operative photographs on day five in all but the original protocol. BiMo, Cal; Doc. 13761W