Help for Researchers and Study Personnel

Introduction

• Physicians may prescribe drugs for the indications approved by the FDA in regulator medical practice. Physicians also may prescribe drugs for "off-label" use, or use outside the FDA-approved indication.

• However, when there is any use of a drug in research except the use of a marketed drug in the course of medical practice, FDA regulations apply to the research and an Investigational New Drug (IND) number from the FDA is required (unless the research meets certain criteria)

• Examples where an IND is required include, but are not limited to clinical investigations to test the safety and effectiveness of:

• • new route of administration
  • new dosage level
  • use in a way that increases risk
  • use to develop data for labeling change or NDA for new application

• If investigators have questions about whether a study involving drugs falls under FDA jurisdiction, or whether an IND is required, please contact the Ethics and Human Research Protection Program at DOH or the FDA.

Examples

• Example of a new route of administration: An HIV medication is FDA-licensed for intramuscular injection. A clinical investigation is proposed to test the bioequivalence, safety, and effectiveness of once per day oral administration.
• Example of a new route of administration: An tuberculosis medication is licensed for delivery every day. A clinical investigation of a new formulation for once per week use to improve adherence to directly observed therapy.
• Example of a new dosage level: A vaccine to prevent hepatitis is licensed for use in a specific population at a specific dose. A clinical investigation is proposed to see whether a higher dose is safe and effective in a subset of the population for which the drug is licensed. The increased dose may increase risk of side-effects.
• Example of a use in a way that may increase risk: An attenuated live virus vaccine effective against H5N1 is being tested in healthy patients. A clinical investigation is proposed to test safety and effectiveness in immunocompromised patients.
• Example of a use to develop data for labeling change or NDA for new application: A live-virus influenza vaccine delivered through a nasal inhaler is licensed for adult use. A clinical investigation is proposed to test whether the drug is safe and effective for pediatric use.
• Example of a use to develop data for labeling change or NDA for new application: A new antiviral drug to treat HIV has FDA approval for use in "experienced" HIV patients. An investigator is conducting a new clinical investigation on behalf of a pharmaceutical sponsor to test whether the drug is safe and effective in newly-infected HIV patients compared with a standard multi-drug regimen.

Verification of the IND

Investigations need to provide documentation verifying the IND, unless the research meets FDA criteria exempting the research from IND requirements. Documentation must include one or more of the following:

• Supported by the commercial sponsor protocol (IND number on study protocol)
• Communication from the commercial sponsor
• Communication from the FDA

Note:

• An investigator’s brochure should not be used because one investigator brochure often serves multiple INDs
• Applications without verification of the IND will be returned.

Investigator-Initiated Studies

The Department of Health does not allow DOH personnel to engage in investigator-initiated studies, unless the investigator has retained a contract-research organization (CRO), or unless an outside institution (for example, CDC or a university) is assuring that all FDA-required sponsor responsibilities are met. Investigations conducting investigator-initiated studies should provide documentation of how FDA-required sponsor-responsibilities are met.

• The protocol description is a BRIEF summary that describes the specific objectives of the proposed research in plain language understandable to all DOH IRB committee members.
• Write in plain language, and translate technical terms into easily understood langauge. Avoid using jargon, technical terms, or scientific language.
• The description should be written in a way that is understandable to members from the local community, non-scientists, as well as scientists with varied backgrounds.
• For consistency in the review of research, the DOH IRB requires that research plans be submitted in the form of a research protocol. A protocol serves as the reference point for review of a DOH IRB application. The IRBWise application is not intended to serve as the research protocol/plan; rather, it is an overview of the proposed project.
• Investigators must attach a research protocol that provides information sufficient to allow the IRB to make required regulatory determinations. Information in the protocol should include, but not necessarily be limited to the following:
  • background
  • rationale and specific aims
  • description of research methods
  • inclusion/exclusion criteria
  • enrollment and retention plans
  • study procedures
  • plans for safety monitoring
  • plans for reporting problems
  • plans for follow-up and providing information to participants
  • record retention
  • See Section VI, Attachments, below