Docket Management
Docket: 01D-0489 - Draft Guidance: Clinical Trial Sponsors on the Establishment & Operation of Clinical Trial DMCs
Comment Number: EC -10

Accepted - Volume 1

Comment Record
Commentor Ms. Mary Eileen McPhee Date/Time 2002-02-19 12:23:20
Organization Cognigen Corporation
Category Company

Comments for FDA General
1. General Comments February 19, 2002 Dockets Management Branch (HFA-305) Food and Drug Administration 5630 Fishers Lane, Room 1061 Rockville, MD 20852 RE: Comments to draft DMC guidance Dear Sir or Madam: The use of population pharmacokinetic/pharmacodynamic analysis in the evaluation of drug exposure-response relationships for safety and efficacy is an evolving area of scientific and FDA interest. These analyses require sparse blood sampling to measure plasma drug concentrations and play an increasingly important role in assessing drug safety. Highlighting this importance by adding the Clinical Pharmacology Group as a possible oversight group in Section 3 could further the development of this type of research. The assembly of drug dosing and plasma concentration data, and preparation for analysis can be a time consuming activity. It will be critical that data assembly and pharmacokinetic analysis be completed in real-time in order to impact safety surveillance. Real time assembly and analysis can provide timely evaluations of drug/drug interactions, lab toxicities, demographics and adverse events with exposure data, thereby facilitating the safety review by data monitoring committees. Expanding on these critical components in Section 4 [committee composition] could bring about a timely, more robust safety evaluation. The creation of the guidance on DMC functions also provides an important opportunity to further emphasize and operationalize several key points stated in the “Population Pharmacokinetics” guidance (Feb 1999). The previous guidance states that “evaluation of pharmacokinetic data can provide the safety data monitoring board with insight into drug exposure safety evaluations and drug-drug interactions”. The use of real-time data assembly is also described to permit timely evaluation of data while the trial is on-going. Although the current draft guidance suggests that a clinical pharmacologist on the DMC may be helpful for selected situations where the investigational drug exhibits variability in absorption/excretion (Section 4), we would propose broader inclusion of this type of scientist for the purposes stated above. Routine evaluation of these relationships would provide important knowledge regarding drug safety earlier in the development process. Thank you for your attention. These comments are respectfully submitted on behalf of Cognigen Corporation, Buffalo, New York. Authors: Mary Eileen McPhee, RN, MS Elizabeth Ludwig, PharmD, Thaddeus Grasela, PharmD, PhD,

EC -10