Clinical investigator receives 2-item 483 for inadequate case histories: Lee Schwartzberg, M.D., Memphis, TN, New Orleans, LA, District.

Lee Schwartzberg, M.D., Memphis, TN, received a two-item 483 in a recent inspection because he failed to prepare or maintain adequate case histories with respect to observations and data pertinent to the investigation.

Investigator Emily Smith from the New Orleans, LA, District Office conducted the audit.

The EIR stated that page 22 from the case report file (CRF) for one study subject "shows that vital signs were not taken for Cycle 1, Day 1. Source data shows 'not done per error,' and under comments in the CRF there is an explanation, 'Dosing vital signs cycle 1.'"

Also, page 22 from another CRF showed that some but not all of the dosing vital signs were taken. "Vital signs were not taken at the end of the [undisclosed] infusion, at the end of the [undisclosed] infusion, nor at 30 minutes after the end of the [undisclosed] infusion," she wrote.

Also, the report noted in this case that the record of the infusion showed that treatment began at 13:00 and was completed at 17:00, so the treatment infusions were not terminated early.

Next, for two study subjects, the hematology result pages in the CRFs had no values recorded for any of the tests.

"Management checked on the missing chemistry results during the inspection. They told me that the samples for this subject were drawn and analyzed by the Desoto laboratory. They reviewed their results but found that the analyses were not done. Serum samples are maintained for a week only, so there is no specimen available to perform analysis now," according to the EIR.

Also, "after the clinical study began, the clinical research department found that they needed to revise their worksheet for recording vital signs during infusion of study chemotherapy drugs. The new form includes spaces for the temperature readings." These observations were noted at the end of the inspection, so the research coordinator did not have time to investigate why these analyses were not performed.

The 483 next cited the researcher because "information necessary for submission of required financial disclosure statements to FDA was not provided to the sponsor."

For example, the EIR noted that two sub-investigators in one study did not complete their financial disclosure forms.

The FDAer wrote: "My initial review of the financial disclosure forms for the [undisclosed] study found question 1 not marked for sub-investigator Scott Baum, M.D. A review of the same form at ACORN showed that it was not marked, either."

After verifying with management that these two forms were incomplete, the research coordinator said she would get them completed, the FDAer stated.

Another observation not noted on the 483 was that a review of bodily systems was not done for one patient on cycle 5, day 1. "The staff looked into this and found that treatment was held for a week because of neutropenia. When he came back for treatment, the patient's blood counts were satisfactory, and he had no new complaints. A full review of systems was completed on his previous visit on Aug. 25, 2004."

The EIR also noted that the establishment's subject records included patient medical charts, drug accountability records, and a regulatory binder containing correspondence with the sponsor and IRB.

"Patient charts consist of doctors' orders, doctors' notes, concomitant medications log, past medical history, consultation and hospital notes, research progress notes, radiological reports, correspondence from other doctors, biopsy reports, surgery reports, adverse events and lab results," the FDAer stated.

There were original copies of lab reports, ECGs and radiological reports in the patients' medical charts to substantiate the information in the CRFs. Also, the site kept a copy of the inclusion/exclusion criteria in the patient's chart along with the data for meeting the criteria.

Regarding informed consent, "all study subjects signed an informed consent prior to their treatment in the clinical study. The first study subject signed his/her informed consent on May 7, 2004, which was after the IRB approved the study on March 9, 2004." The investigator from FDA also noted that all serious adverse events, including the death of a study subject who died shortly after being pulled from the study, were reported to the IRB.

Regarding records retention, "the study subjects' medical charts are available at the main clinic site ... or at one of the satellite sites."

Also, "the facility has written procedures that define the authority and responsibility of the principal investigators, sub-investigators, the clinical research nurse or coordinator and all other personnel involved in clinical studies."

Subject records included source documentation for the clinical studies, patient charts, drug accountability logs, and regulatory binders. "Results of all tests and procedures are contained in the patient charts, as well as treatment and assessments, physicians' and nurses' notes, medical histories and correspondence from other physicians and hospitals. The medical records were thorough, legible and organized into sections," according to FDA records.

It was noted that medical records were maintained in their file room, which was next door to the room where the audit was conducted. The drug accountability records were in the pharmacy which was also on the same floor. Other records were maintained in the clinical research department, which was also on the same floor as the room where the inspection was performed.

Lee Schwartzberg, M.D., Memphis, TN, 2/18-3/8/05, Doc. 110026M, $22 plus retrieval.