FAQs About Drug Studies

A drug is, among other things, an article (other than food) that:

• is intended for use in the diagnosis, cure, mitigation, treatment, or prevention of disease
• is intended to affect the structure or any function of the body
• achieves its primary intended purpose through chemical action in the body or by being metabolized

Biological products may also be considered drugs within the meaning of the FD&C Act.  It is important to note that the definition of drug is not limited to compounds intended for a therapeutic purpose.  The definition also includes compounds intended to affect the structure or function of the body, without regard to whether the compound is intended to influence a disease process.  For example, the definition includes compounds administered to healthy subjects to blunt or provoke a physiologic response or to study the mechanism of action or metabolism of a drug.

An Investigational New Drug (IND) application allows a sponsor to lawfully use an investigational drug for the purpose of conducting a clinical investigation of that drug.

An investigational drug can be an unapproved drug or an approved product being studied for a new indication or in a new patient population.

The FDA’s objectives are to assure data quality and study subject safety.  In an initial IND submission, the sponsor provides:

• Pharmacology, toxicology, and manufacturing information used to assess whether the product is reasonably safe for initial testing in humans
• A clinical protocol and, if applicable, an Investigator Brochure
• A signed agreement to adhere to informed consent, IRB review, and general IND regulations

Once approved, an IND grants the sponsor an exemption from the federal statute that prohibits shipping an unapproved drug in interstate commerce.

A clinical investigation is any experiment in which a drug is administered or dispensed to, or used involving, one or more human subjects.

The sponsor of a clinical investigation that is not otherwise exempt from the IND requirements is responsible for submitting an IND application to FDA and obtaining Institutional Review Board (IRB) approval before the study can begin.

A clinical investigation of a drug is exempt from the IND requirements if all of the following criteria are met:

• The drug product is lawfully marketed in the United States.
• The investigation is not intended to be reported to the FDA in support of a new indication for use or any other significant change in the labeling for the drug.
• The investigation is not intended to support a significant change in the advertising for a prescription drug product.
• The investigation does not involve a change in route of administration, dosage level, or patient population, or other factor that significantly increases the risks (or decreases the acceptability of the risks) associated with use of the drug product.
• The investigation is conducted in compliance with the requirements for IRB review (21 CFR 56) and informed consent (21 CFR 50).
• The drug may not be represented as safe or effective for the purposes for which it is under investigation, nor may it be commercially distributed or sold.

Historically, assessing whether a particular use of a drug in a clinical investigation significantly increases the risk, or decreases the acceptability of the risk, compared to its approved use, has been the most difficult issue in deciding whether an IND is needed for a clinical investigation of a marketed drug.  If needed, specific guidance is available from the FDA.

A sponsor is a person who takes responsibility for and initiates a clinical investigation.  A sponsor may be an individual, a pharmaceutical company, a government agency, an academic institution, or other organization.  The sponsor submits and maintains the IND.

An investigator is an individual who actually conducts a clinical investigation (i.e., under whose immediate direction the drug is administered or dispensed to a subject).

A sponsor-investigator is an individual who both initiates and conducts an investigation and under whose immediate direction the investigational drug is administered or dispensed.  The term does not include any person other than an individual.

• Phase 1 – Phase 1 includes the initial introduction of an investigational new drug into humans. These studies are usually conducted in healthy volunteer subjects. These studies are designed to determine the metabolic and pharmacological actions of the drug in humans, the side effects associated with increasing doses, and, if possible, to gain early evidence on effectiveness. Phase 1 studies also evaluate drug metabolism, structure-activity relationships, and the mechanism of action in humans. The total number of subjects included in Phase 1 studies is generally in the range of twenty to eighty.
•  Phase 2 – Phase 2 includes the early controlled clinical studies conducted to obtain some preliminary data on the effectiveness of the drug for a particular indication or indications in patients with the disease or condition. This phase of testing also helps determine the common short-term side effects and risks associated with the drug. Phase 2 studies usually involve several hundred people.
•  Phase 3 – Phase 3 studies are intended to gather the additional information about effectiveness and safety that is needed to evaluate the overall benefit-risk relationship of the drug. Phase 3 studies also provide an adequate basis for extrapolating the results to the general population and transmitting that information in the physician labeling. Phase 3 studies usually include several hundred to several thousand people.

• Sponsor-Investigator IND – An application submitted by a physician who both initiates and conducts an investigation, and under whose immediate direction the investigational drug is administered or dispensed.
• Emergency Use IND – A vehicle through which the FDA can authorize the immediate shipment of an experimental drug for a desperate medical situation. Emergency Use INDs are generally reserved for life-threatening situations in which no standard acceptable treatment is available and there is not sufficient time to obtain IRB approval.  Emergency Use INDs are sometimes also called “single-patient” INDs.
• Treatment IND – An application submitted for experimental drugs showing promise in clinical testing for serious or immediately life-threatening conditions while the final clinical work is conducted and the FDA review takes place.

Emergency Use and Treatment INDs are also known as “Compassionate Use” INDs, but the term “Compassionate Use” is not found in the IND regulations.