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May 17

No 2: Medical Practice vs. Clinical Research

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No. 2: May 17-21, 2010

Medical Practice vs. Clinical Research


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.


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).


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.

Comments (7)
written by richw3, May 10, 2010
If the doctor uses a treatment he believes to be appropriate off label, that is not research. That is the practice of clinical medicine. If the doctor collects data, whether or not the drug is approved for this use in this patient population, that is research. In the first example, the FDA may be interested, e.g., methotrexate for the common cold. In the second example, depending on the data collected, the patient population and the treatment, there may need to be IRB approval (or the IRB could decide that it is exept research) whether the doctor is a member of an academic faculty (i.e., institutional) or in private practice.
written by Cal, May 10, 2010
The doctor appears to understand that he will be conducting research. His question is a much narrower one of whether he is required to obtain an IND. The respondant appears to assume that the new use increased the risk (or decreases the acceptability of the risk) which would require an IND. A cursory reading of the scenerio though, suggests that it is not clear that this use would increase patient risk. And because Dr. McGill does not appear to intend to seek an indication for this use, I'm not sure he would need an IND. That is an entirely different issue from seeking IRB approval, which of course would be required.
written by swan33, May 10, 2010
my read is the same as cal's-
written by Bob Ward, May 10, 2010
This study by Dr. McGill, if approved by an IRB, satisfies the 5 criteria needed to qualify for a waiver of the IND as described in 21 CFR 312.1-7. There is no safety or dosage issue. These studies are not intended to be submitted to the FDA for a new label or used to commercialize a new indication.
written by Cal, May 10, 2010
That's where a question arises. I agree that the study does not appear to represent an increase in patient risk over the approved use. Presumably Dr. Arbit disagrees. If he is correct, then the study does not satify the 5 criteria for an IND exemption. If we are correct, it does. The really interesting question here is what to do if Dr. McGill and the clinical trials office (acting in an advisory capacity) disagree.
Stop unnecessary research
written by Richard Goldschwein, May 27, 2010
physicians should be treating patients, not conducting research. Research just increases medical costs without benefit to patients, and exacerbates the physician shortage that we already have
written by Dr. Arbit, May 27, 2010
The assessment of IND applicability for this protocol could have gone either way. Since it was not abundantly clear that this study should be IND exempt an IND was submitted to the FDA. The FDA agreed that an IND is indeed needed, that is, the study did not meet the criteria for IND exemption.

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