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Clinical Trials

A research study in which one or more human subjects are assigned to one or more interventions (which may include placebo or other control) to evaluate the effects of those interventions on health-related biomedical or behavioral outcomes.

Clinical trials are used to evaluate the effectiveness and safety of medications or medical devices by monitoring their effects on groups of people. Government agencies (FDA in the US) approve or disapprove new treatments based on clinical trial results.

Usually volunteers are recruited, although in some cases research subjects may be paid. Subjects are generally divided into two or more groups, including a control group that does not receive the experimental treatment, receives a placebo (inactive substance) instead, or receives a tried-and-true therapy for comparison purposes.

There are four possible outcomes from a clinical trial:

Positive trial = The clinical trial shows that the new treatment has a large beneficial effect and is superior to standard treatment.

Negative trial = The clinical trial shows that a new treatment is inferior to standard treatment.

Non-inferior trial = The clinical trial shows that that the new treatment is equivalent to standard treatment. Also called a non-inferiority trial.

Inconclusive trial = The clinical trial shows that the new treatment is neither clearly superior nor clearly inferior to standard treatment.

Clinical trials are usually organized in phases:

PHASE 0: Is an exploratory investigational new drug study and also known as a “microdosing” study. Exploratory trials to establish whether the agent behaves in humans as was expected from preclinical animal studies, to gather preliminary data on pharmacodynamics or pharmacokinetics, to select promising lead candidates, or to explore biodistribution characteristics. Phase 0 is intended to speed drug development as part of the FDA Critical Path Initiative by quickly filtering out ineffective drugs early in the development process. (No therapeutic or diagnostic intent.)

PHASE I: Initial studies to determine the metabolism and pharmacologic actions of the agent in humans, the side effects associated with increasing doses, and to gain early evidence of effectiveness.

PHASE I/II (Device – Pilot): Some trials combine Phase I and Phase II, and test both efficacy and toxicity (safety, dosage levels, and response to new treatment).

PHASE II: Controlled clinical studies conducted to evaluate the effectiveness of the agent for a particular indication or indications in patients with the disease or condition under study and to determine the common short-term side effects and risks.

PHASE II/III: Some trials combine Phase II and Phase III. This phase tests for both efficacy and overall benefit versus risk. The new treatment is compared to a standard treatment regimen.

PHASE III (Pivotal): Expanded controlled and uncontrolled trials after preliminary evidence suggesting effectiveness of the agent/test article has been obtained and are intended to gather additional information to evaluate the overall benefit-risk relationship and provide an adequate basis for physician labeling. Compares new agent/test article against commonly used agents/test articles.

PHASE IV: Post-marketing studies to delineate additional information including the agent’s risks, benefits, comparative effectiveness, and optimal use. These studies are designed to monitor the effectiveness of the approved intervention in the general population and to collect information about any adverse effects associated with widespread use.

EFPIA published this educational video about clinical trials:

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