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No. 2: May 17-21, 2010

Medical Practice vs. Clinical Research

Scenario:

Dr. McGill is a transplant surgeon in a university who has treated hematopoietic stem cell (HSC) transplant patients with transfusional hemosiderosis with deferasorix (Exjade®). His rationale is this drug is indicated to treat transfusional hemosiderosis in patients with β-thalassemia, chronic anemias, and sickle cell disease. His results treating HSC transplant patients appear to be clinically acceptable. He realizes that this is an off-label use and would like to conduct a randomized clinical trial to support the way he is using it.

He has never conducted a clinical research study previously and discusses this with the clinical trials office at the university. He argues that since this is a market drug and he uses it routinely in his medical practice FDA oversight is not necessary.

Issue:

HSC transplant patients are a different population from the populations the drug is approved for. Dr. McGill is no longer practicing medicine (regulated by state medical boards) but is conducting clinical research (regulated under the jurisdiction of the FDA).

Solution

The use does not meet the criteria for IND exemption. Therefore an IND application is required to conduct this study. Dr. McGill will also need to obtain IRB approval and patient informed consent. This is an investigator-initiated study. Dr. McGill is the IND sponsor-investigator and must comply with the FDA regulations for both an IND sponsor and IND principal investigator.

Lesson learned:

• Clinical trials are not to evaluate a medicine under actual medical practice conditions, but rather under selected and often artificial conditions to answer best the trial’s objectives.

Controlled clinical trials cannot by definition mimic actual medical practice conditions.

[Bert Spilker, Guide to Clinical Trials, 1996, p.554]

• The use of a lawfully marketed drug that involves a route of administration or dosage level or use in a patient population or other factor that significantly increases the risks (or decreases the acceptability of the risks) may be considered an investigational drug requiring the submission of an IND.

Pertinent Rule/Regulation

The Code of Federal Regulations describes IND applicability, responsibilities, records, and recordkeeping for sponsors and investigators [21 CFR 312]. The requirements for IRBs and informed consent are also in these regulations [21 CFR 56 and 50, respectively].

Comments by Harvey M. Arbit, PharmD, MBA, president of Arbit Consulting, LLC. He specializes in FDA regulatory affairs related to investigator-initiated IND and IDE research.