New Cancer Treatments : Special Needs, Off-Label Drugs

by National Cancer Institute

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Getting Treatments to Patients Who Need Them

Not everyone is eligible to participate in a clinical trial. Some patients do not fit the exact requirements for studies, some have rare forms of cancer for which only a limited number of studies are underway, and others are too ill to participate. Working with the National Cancer Institute (NCI) and other sponsors, the U.S. Food and Drug Administration (FDA) has established special conditions under which a patient and his or her doctor can apply to receive cancer treatments that have not yet been through the approval process. In the past, these special case applications for new treatments were grouped under the name compassionate uses. More recently, such uses have expanded to include more patients and more categories of experimental or investigational treatments.

Access to Investigational Drugs

The process of new drug development has many parts. In the United States, until a drug has been approved by the FDA, it can generally be obtained only through several mechanisms: enrollment in a clinical trial studying the drug, an expanded access program, or special exemption/compassionate use programs.

Group C Drugs

In the 1970s, researchers from the NCI became concerned about the lag between the date when an investigational drug was found to have anti-tumor activity and the time that drug became available on the market. Working with the FDA, the NCI established the Group C classification system to allow access to certain drugs.

Group C drugs are provided to properly trained physicians who have registered using a special form to assure that their patient qualifies under guidelines - or protocols - for the drug. Each Group C drug protocol specifies patient eligibility, drug use, and how information about the patient's use of the drug should be reported.

Group C designation (now called Group C/Treatment INDs) speeds new drugs to patients who need them most. The process also allows the NCI to gather important information on the safety and activity of the drugs as they are used in the "real world" prior to their final FDA approval. Group C drugs are always provided free of charge, and the Centers for Medicare and Medicaid Services provides coverage for care associated with Group C therapy.

Treatment INDs

In 1987, the FDA began authorizing the use of new drugs still in the development process to treat certain seriously ill patients. In these cases, the process is referred to as a treatment investigational new drug application (Treatment IND). Clinical trials of the new drug must already be underway and have demonstrated positive results that can be reproduced. The FDA sets guidelines about what constitutes serious and life-threatening illnesses, how much must already be known about a drug's side effects and benefits, and where doctors can obtain the drug for treatment. For many seriously ill patients, the risks associated with taking a not-yet-completely proven drug are outweighed by the possible benefits.

Accelerated Approval

Accelerated approval is the short-hand term for the process by which the FDA quickly conducts its review of new treatment applications while also putting new safeguards in place. Accelerated approval is based on surrogate endpoint judgments: the FDA can grant marketing approval to drugs and treatments that, according to certain indicators, prove they are likely to have beneficial effects on a disease or condition, even before such direct benefits have been shown clinically. Accelerated approval does not mean that additional clinical trials are not needed or that the FDA stops gathering information about the effects of the drug; a follow-up study is required to demonstrate activity by more conventional endpoints.

Q&A: Off-Label Drugs

What is off-label use?

Off-label use refers to the use of an approved treatment for any purpose, or in any manner, other than what is described in the treatment's labeling. Off-label use of an approved treatment is not the same as expanded access or special exemption, which are mechanisms allowing patient access to investigational treatments not yet approved by the FDA.

New treatments can be legally marketed in the United States only after approval by the U.S. Food and Drug Administration (FDA). Approval is the final stage of a multi-year process of study and testing to establish that the new treatment is safe and effective for the proposed use. (The FDA maintains a searchable database of approved cancer drugs 4, complete with labeling information.)

A cancer treatment rarely receives approval for general use against cancer. Instead, a treatment is approved for use in treating a specific stage of a particular kind of cancer, for which it has been tested in patients. The specific approved use is called an indication. The indication is described in the labeling for the drug or biologic, which consists of a printed insert included in the treatment's packaging. The insert also describes in detail the chemical composition of the treatment, how it works in the body, and the possible adverse effects of taking it.

However, the FDA - although responsible for ensuring that a treatment is safe and effective for the specific approved indication - does not regulate the practice of medicine. This means that once the FDA approves a treatment, licensed physicians can prescribe it for any purpose they consider medically appropriate.

Off-label uses may include giving an approved treatment:

• for a disease other than the disease it is approved for,
• at a different dose or frequency than specified in the product's labeling, or
• to treat a child when the product is approved to treat adults.

An off-label use of a product can cease to be off label if the product's maker submits a supplemental application and obtains FDA approval for the new use. The FDA encourages, but does not require, drug makers to do this.

To submit a supplemental application, the drug maker must conduct studies to show that the product is safe and effective for the proposed new use. Unless the drug company expects to gain a significant commercial benefit from expanded approval of a drug already on the market, it may decide not to invest time and money in such additional studies.

hy is off-label use of drugs so common in cancer treatment?

A 1991 study by the U.S. General Accounting Office found that one-third of the drug treatments performed by cancer doctors were off-label; more than half of cancer patients received at least one drug for an off-label indication. A 1997 survey of 200 cancer doctors by the American Enterprise Institute and the American Cancer Society found that 60 percent of them prescribed drugs off-label. Frequently the standard of care for a particular type or stage of cancer involves the off-label use of one or more drugs.

About the Author

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