Special Issues in FDA-Regulated Studies: The Good, the Bad, and the Ugly - PowerPoint PPT Presentation

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Special Issues in FDA-Regulated Studies: The Good, the Bad, and the Ugly

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Special Issues in FDA-Regulated Studies: The Good, the Bad, and the Ugly C. Karen Jeans, MSN, CCRN, CIP COACH Program Analyst VA Office of Research & Development – PowerPoint PPT presentation

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Title: Special Issues in FDA-Regulated Studies: The Good, the Bad, and the Ugly


1
Special Issues in FDA-Regulated Studies The
Good, the Bad, and the Ugly
  • C. Karen Jeans, MSN, CCRN, CIP
  • COACH Program Analyst
  • VA Office of Research Development

2
What this Talk will Cover
  • IND Issues
  • Application Issues and the Role of the IRB
  • IND applicability in Special Situations
  • Oncology?
  • Nutritional Supplements?
  • Air?
  • Clinical Trial Registry

3
FDA Definition Clinical Investigation
  • Use of a drug other than the use of an approved
    drug in the course of medical practice (21 CFR
    312.3)
  • Use of a medical device other than the use of an
    approved medical device in the course of medical
    practice (Food, Drug and Cosmetic Act
    530(g)(3)(a)(i))
  • Gather data that will be submitted to or held for
    inspection by FDA in support of a FDA marketing
    permit for a food, including a dietary supplement
    that bears a nutrient content claim or a health
    claim, an infant formula, a food or color
    additive, a drug for human use, a medical device
    for human use, a biological product for human
    use, or an electronic product. (21 CFR 50.1(a),
    or 21 CFR 56.101(a))

4
Investigational New Drug (IND) Application?
  • Affirms a body of knowledge about the
    manufacturing, pharmacology, and toxicology of
    the drug to support its use in human testing
  • Requires that the clinical investigation(s) be
    performed in accordance with Good Clinical
    Practice (GCP)
  • Provides an additional level of protection
    through FDA oversight
  • An IND is required when an unapproved drug or
    biologic is used in a clinical investigation

5
IND Issues
  • IND Issues
  • Is it necessary for an IRB to review IND
    documentation?
  • Form FDA 1571 Investigational New Drug
    Application (IND)
  • IND Application

6
IND Applicability
  • Problems with determining whether an IND applies
  • Key issue approved drugs used in unapproved
    uses
  • Oncology
  • Nutritional Supplements
  • Medical Gases

7
IND Exemptions
  • Clinical exemption of a drug product that is
    lawfully marketed in the United States is exempt
    from 21 CFR 312 if all apply
  • The investigation is not intended to be reported
    to the FDA as a well-controlled study in support
    of a new indication for use nor intended to be
    used to support any other significant change in
    the labeling of the drug
  • The investigation is not intended to reported to
    the FDA as a well-controlled study in support of
    a new indication for use nor intended to be used
    to support any other significant change in the
    labeling for the drug
  • 21 CFR 312.2(b)(i-iv)

8
IND Exemptions (cont.)
  • The investigation does not involve 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) associated with
    the use of the drug product
  • The investigation is conducted in compliance with
    the requirements for institutional review set
    forth in part 56 and with the requirements for
    informed consent set forth in part 50
  • 21 CFR 312.2(b)(i-v)

9
Oncology Drugs
  • 1996 Agency Cancer Initiative
  • Reason Many sponsor-investigators submitting
    INDs for exploratory studies of off-label
    indications
  • IRBs incorrectly believed IND required
  • Pharmaceutical manufacturer provided drug free of
    charge
  • Majority of sponsor-investigator IND submissions
    for marketed cancer drugs were exempt

10
Agency Determination
  • Is risk significantly increased?
  • Examine parts of the protocol
  • Dose
  • Schedule
  • Route of administration
  • Patient population

11
Is it exempt from IND requirements?
  • Phase 1 oncology trial of a marketed drug
  • Studies of chemotherapy given after surgery to
    remove cancer
  • Study of high-dose therapy in cancer patients
  • Studies of cytotoxic drugs

12
Nutritional Supplements
  • Regulated under the Dietary Supplement Health and
    Education Act of 1994 (DSHEA)
  • Do not require FDA approval prior to marketing

13
Is St. Johns Wart a Drug?
  • Scenario
  • Investigator calls the IRB office stating that
    she is submitting a protocol for review at the
    next IRB meeting using St. Johns Wart. She is
    going to study whether St. Johns Wart reduces
    cyclosporine levels in patients after kidney
    transplant. She doesnt know where to list it on
    the IRB application.
  • Question Should the investigator list it
    on the IRB application as a drug?

14
Is St. Johns Wart a test article?
  • Test article
  • Any drug (including a biological product for
    human use), medical device for human use, human
    food additive, color additive, electronic
    product, or any other article subject to
    regulation under the Food, Drug, and Cosmetic Act
    or under sections 351 and 354-360F of the Public
    Health Service Act.
  • 21 CFR 50.3(j)

15
Is Air a Drug?

16
Medical Gases
  • Scenario
  • During the IRB meeting, the IRB is reviewing
    a protocol involving the administration of an
    investigational new drug vs. usual care. The
    investigator is also going to use supplemental
    CO2 (carbon dioxide gas) during blood flow scans.
    They ask you as the IRB Administrator whether
    they submitted any materials about the IND status
    of the gas. The investigator did not, and the
    IRB Chair wants to know why didnt the IRB
    Administrative staff didnt follow-up on this
    before the IRB convened meeting.
  • Question Was this a reasonable
    expectation?

17
IND applicability
  • Not black and white
  • Regulations
  • Use in protocols
  • Investigators should communicate with FDA
  • Sponsor has ultimate responsibility

18
Clinical Trial Registration
  • 1997 Section 113 of the FDA Modernization Act
    of 1997
  • Create a public resource for information on
    studies of drugs, including biological drug
    products, to treat serious or life-threatening
    diseases and conditions conducted under FDAs IND
    regulations
  • September, 2007 Food and Drug Amendment Act
  • Expanded scope of clinical trials that must be
    registered
  • Established civil monetary penalties

19
What must be registered?
  • Federal Law
  • International Committee of Medical Journal
    Editors (ICMJE) requirements
  • FDA, NIH, and ICMJE recommendations 

20
FDA requirements
  • Trials of Drugs and Biologics
  • Controlled clinical investigations, other than
    Phase 1 investigations, of a product subject to
    FDA regulation, and
  • Trials of Devices
  • Prospective clinical studies of health outcomes
    comparing an intervention with a device against a
    control in human subjects (other than small
    clinical trials to determine the feasibility of a
    device, or clinical trials to test prototype
    devices where the primary outcome measure relates
    to feasibility and not to health outcomes and
    pediatric postmarket surveillance studies, as
    required under the Federal Food, Drug and
    Cosmetic Act.
  • Public Law 110-85, Title VIII

21
FDA requirements
  • Form FDA 3674
  • Certification of Compliance, under 42 U.S.C.
    282(j)(5)(B), with Requirements of
    ClinicalTrials.gov Data Bank
  • (42 U.S.C. 282(j))
  • When is it filed?
  • Current issues with interpretation

22
International Committee of Medical Journal
Editors (ICMJE) Requirements
  • Any research study that prospectively assigns
    human participants or groups of humans to one or
    more health- related interventions to evaluate
    the effects on health outcomes to be registered.
        
  • Health-Related interventions include any
    intervention used to modify a biomedical or
    health-related outcome (for example, drugs,
    surgical procedures, devices, behavioral
    treatments, dietary interventions, and
    process-of-care changes). 
  • Health Outcomes include any biomedical or
    health-related measures obtained in patients or
    participants, including pharmacokinetic measures
    and adverse events.
  • Includes Phase I investigations and
    investigations which are not biomedical clinical
    trials.

23
FDA, NIH, and ICMJE Recommendations
  • FDA and NIH
  • Registration of all trials, regardless of whether
    it is required by law.
  • ICMJE
  • Those who are uncertain whether their trial meets
    the ICMJE definition should err on the side of
    registration if they wish to seek publication in
    an ICMJE journal. 

24
Clinical Trial Registration
  • Who is responsible for ensuring clinical trial
    registration as required by FDA for the
    following?
  • Industry-sponsored clinical trials
  • Sponsor-Investigator initiated clinical trials
    that are not VA funded
  • VA funded programs

25
Summary

26
How to Contact FDA For Questions
  • 1-888-INFO-FDA (1-888-463-6332)
  • Help Desk
  • Drugs http//www.fda.gov/cder/comment.htm
  • Devices
  • http//www.fda.gov/cdrh/comment4.html
  • Biologics
  • http//www.fda.gov/cber/pubinquire.htm
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