Viola Sellman
Chief, Program Enforcement Branch II
Division of Bioresearch Monitoring
Office of Compliance
Center for Devices and Radiological Health
Food and Drug Administration
2098 Gaither Road, HFZ-312
Rockville, Maryland 20850

Dear Ms. Sellman:

On behalf of the American Association for Clinical Chemistry (AACC), I would like to thank you and your colleagues at the Food and Drug Administration (FDA) for the time and effort you have put forth explaining to us, and the laboratory industry, the agency's December 17, 1999 guidance document "Regulating In Vitro Diagnostic Device (IVD) Studies." Although we share the FDA's desire to protect patient confidentiality, we continue to have reservations about the agency's new policy on the use of "excess" specimens and its potentially adverse effect on patient care.

According to the FDA, its auditors may need, at times, to verify that the patient samples used in clinical trials, and reported as part of PMA or 510(k) submissions, meet the parameters set forth in the study. The only way the agency believes it can validate this information is by having direct access to the original source documents containing the data (i.e., the patient's medical record). Without that patient's consent, however, the agency asserts that it does not have the authority to review that record and, therefore, could not review the data, which could affect the research's admissibility as part of the submission.

Although investigators obtain informed consent from patient's participating in prospective clinical trials, they typically have not been required to do so in design verification (demonstration that the design output meets the design input) and validation studies (demonstration that the design output meets the end users' needs) using "excess" patient specimens. These studies do not require additional samples from the patient, do not include patient identifiers and do not report back data to the patient or the physician. The investigator uses only patient samples that would normally be discarded, as well as the clinical information associated with the specimen (the investigator has access to such information as a member of the medical staff), such as the physician's diagnosis and/or the test results.

Historically, Institutional Review Boards (IRBs) have waived the informed consent requirements for verification and validation studies for a variety of reasons, such as: (1) the retrospective nature of the study; (2) the minimal risk to the patient (the testing data are not reported back to the patient or included in the patient's chart); and (3) the study could advance patient care. These reasons are justified based on 45 CFR 46.116 (c &d)-the provisions used by most IRBs as the framework for reviewing research proposals. AACC supports the FDA's desire to protect patient privacy, but does not believe requiring informed consent for using "excess" specimens is the answer.

We are concerned that requiring patient consent for the use of an individual's "excess" specimen will result in sample selection bias, thereby diminishing the value of the studies being performed. Many individuals, especially in emergency room and critical care settings, may be barred from participating in clinical studies because their physicians and/or IRBs may consider the time needed to explain and obtain informed consent as disruptive to providing immediate patient care.

Further, it is simply not practical for all health care providers to have personnel available 24 hours a day to explain and obtain patient consent for leftover samples. The only alternative for many institutions would be to use specimens obtained during normal, 9-5 working hours, when someone is available to explain the pertinent issues to the patient and obtain consent. Therefore, requiring individuals to sign a consent form at the time the specimen is collected may result in certain patient populations being systematically excluded from important clinical studies, thus adversely affecting the validity of some comparisons and distorting the overall findings.

One option, which may meet the FDA's desire for greater confidentiality, as well as preserve access to such specimens, would be to permit the use of a certified or other authenticated photocopy-excluding patient identifiers-to serve as a surrogate for the paper chart or source document that the FDA auditors review. This "pedigreed" sample, which would be similar to what is already done with stored samples, would permit the agency to see the necessary data, and confirm the data submitted by the sponsor, without jeopardizing the confidentiality of the patient's record.

In addition, the agency could permit health care institutions, such as hospitals, to include an informed consent statement in their general admission or registration documents, which would permit the use of excess blood specimens for research. The statement could read as follows:

"By signing this document, I approve the use of any excess specimens submitted for clinical laboratory testing for investigational studies or educational purposes, and the gathering of such information from my medical record as would be necessary for the conduct of these activities, as authorized by the Institutional Review Board (IRB) of [Name of Institution]. (The IRB is the government sanctioned authority within the institution designated to protect the rights of patients in ongoing health care studies)."

We believe that the use of this or a like statement (as long as it complies with state law) would permit the use of leftover or excess samples in most instances, as long as the study was reviewed and approved by the institution's IRB.

In summary, AACC recommends that the FDA permit its auditors to review certified copies of the patient record as a surrogate for the source document as a means of conducting its investigations. Further, we believe the inclusion of a generic statement in the health care providers general admission or registration documents could serve as an additional mechanism for addressing this issue or could be adopted in conjunction with the first recommendation.

By way of background, AACC is the principal association of professional laboratory scientists--including MDs, PhDs and medical technologists. AACC's members develop and use chemical concepts, procedures, techniques and instrumentation in health-related investigations and work in hospitals, independent laboratories and the diagnostics industry nationwide. The AACC's objectives are to further the public interest and educational activities and to help maintain high professional standards.

If you would like to meet with AACC members or staff to discuss this option further, please me (919) 684-8724 or Vince Stine, Director, Government Affairs, at (202) 835-8721.




Frank A. Sedor, PhD

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