7-item 483 delivered to clinical investigator for protocol violations.

Kim Hendrick, M.D., Flushing, MI, was hit with a seven-item 483 because the clinical investigator failed to adhere to protocol in the area of independent radiological assessments of sinus X-rays. Investigator Laureen Kononen from the Detroit, MI, District Office conducted the inspection.

"The radiological group listed in the sinus x-ray assessments did not perform radiological interpretations of enrolled subjects as submitted to the sponsor by Dr. Hendrick's office," according to FDA documents. Assessments were noted for several screen failure subjects at that facility.

"Source documentation of x-ray interpretations by the radiological group listed on the assessments does not support the claimed x-ray assessments listed on the sinus xray log sheets provided by Dr. Hendrick's office," the 483 stated.

The doctor's written response disagreed with this observation. "The source documentation supports the fact that, as required by the protocol, a registered radiologist made independent radiological interpretations of sinus x-ray films for all study subjects. The interpretation is documented on written and signed reports submitted to my office for all subjects."

Next, exclusion criteria for study #592 included three or more episodes of sinusitis requiring treatment with an antibacterial agent in the preceding 12 months. One subject was treated with antibiotics for infections involving sinuses on three occasions prior to enrollment. Another subject was treated with antibiotics on three occasions prior to enrollment, as well.

The clinical investigator replied: "Source documentation supports the fact that both subjects wee treated with antibiotics for upper respiratory infections, not sinusitis, thus these subjects met the inclusion criteria for the study."

Further, the report noted that the screen failure log for study #592 did not document the reason for the exclusion as mandated in the protocol.

The response: "The reason for exclusion from the study was documented in the source notes for all subjects that did not meet the inclusion criteria. There is no such mandate within the protocol requiring that this information be documented on the tracking log. As a matter of fact, the sponsor changed the tracking log and eliminated the portion asking for the reason, on the new form."

Also, the protocol stipulated that the same radiologist performed all assessments in the #592 study. Xray assessments, verified as completed for screen failures, all had different radiologists.

The doctor noted in reply that "it is clearly documented in the chart that this patient did indeed have the above referenced adverse events. It was a site error that this was transposed into the case report form and thus to the sponsor. My coordinator, the study monitor and I missed this."

Further, "crossed-out information on source documents did not always have the initial and date of the the person making the correction," the 483 stated. In one study, the original screening log, screen failure log and drug dispensing record had missing dates, dates not put in chronological order, dates were written over and had crossouts.

The researcher disputed this finding as well: "I do not believe that there is any reference in the protocol that chronological order be made as far as numbers and dates are concerned."

She added: "In regard to the progress note program, it was clearly explained and shown that when the dates are within 24 hours of each other, although the roster will show the two separate dates, when printing these out, they have the same date. I also would like to point out that the one who is signing the progress notes reviews the records and any changes are made at that time. Signing and dating the end document covers all changes made at that time by that signature. It is only when changes are later made that initial and dating should be done."

Kim Henderick, M.D., Flushing, MI, 7/29-8/28/03, Doc. 115390, $22 plus retrieval.

Kim Hendrick, M.D., Flushing, MI, Detroit, MI, District Office