New Cancer Treatments Clinical Trials

by National Cancer Institute

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Speed versus Safety in the Approval Process

During the approval process, the FDA classifies as "priority" those treatments that offer significant medical advances over existing therapies. But even in non-priority cases, the FDA's goal is that no more than 10 months will pass between when a complete application is submitted and the FDA has finished its review, either approving the drug or biologic, or providing the sponsor with a complete list of the issues that need to be addressed.

The process is not always smooth, however. Sometimes the FDA requests (or the FDA's advisory panel recommends) additional research or data. Some new approvals have taken as little as 42 days from the time the last part of the BLA/NDA is received; other more difficult applications have spent years in the approval process.

Expert Advice

The FDA relies on a system of independent advisory committees, made up of professionals from outside the agency, for expert advice and guidance in making sound decisions about drug approval. Each committee meets as needed to weigh available evidence and assess the safety, effectiveness, and appropriate use of products considered for approval. In addition, these committees provide advice about general criteria for evaluation and scientific issues not related to specific products. The Oncologic Drugs Advisory Committee (ODAC) meets regularly to provide expert advice on cancer-related treatments and preventive agents.

Each committee is composed of representatives from the the fields of research science and medical practice. At least one member on every advisory committee must represent the consumer perspective.

Final Approval

As the FDA looks at all the data submitted and the results of its own review, it applies two benchmark questions to each application:

• Do the results of well-controlled studies provide substantial evidence of the treatment's effectiveness?

• Do the results show the product is safe under the conditions of use in the proposed labeling? In this context, "safe" means that potential benefits have been determined to outweigh any risks.

Continued Vigilance

The FDA's responsibility for new medical treatments does not stop with final approval. The CDER's Office of Compliance tracks drugs after approval to make sure that drug makers comply with current standards and regulations. CDER's Office of Drug Marketing, Advertising, and Communication monitors new drug advertising to make sure it is truthful and complete. Biologics regulated by CBER are followed with the same vigilance after approval by the Office of Compliance and Biologics Quality as well as the Advertising and Promotional Labeling staff. And through a system called MedWatch 12, the FDA gets feedback from health professionals and consumers on how the new treatments are working, any adverse reactions, and potential problems in labeling and dosage.

Online FDA Resources

The following information from the FDA should help you better understand the drug approval process:

• The CDER Handbook
• Vaccine Product Approval Process
• From Test Tube to Patient: New Drug Development in the U.S.
• Milestones in U.S. Food and Drug Law History
• Drugs Approved for Use With Cancer

Clinical Trials

The Clinical Trials Process

Clinical trials provide the most important information used by the U.S. Food and Drug Administration (FDA) to decide whether a new medical treatment shows "substantial evidence of effectiveness," or whether an already approved treatment can be used effectively in new ways (for example, the drug gemcitabine was at first approved as a treatment for pancreatic cancer but was later tested and approved for use in treating certain types of lung cancer).

The FDA must certify that a treatment has shown promise in the laboratory and in animals before human testing can begin. All clinical trials are supervised by an independent board of experts, which ensures that the sponsor of the treatment can stop the study early if major problems develop or if unexpected benefits are found. The potential benefits and risks of any clinical trial must be carefully weighed by the researchers conducting the study and the patients who decide to participate.

Different Kinds of Clinical Trials

Cancer clinical trials can focus on either treatment or prevention. Treatment trials test new ways of curing or relieving the symptoms of cancer in people who have the disease. Prevention trials enroll people who are at increased risk for developing cancer. In some cases, prevention trials test the effectiveness of an intervention such as a change in lifestyle; others test whether a drug can help to prevent cancer. Using drugs in this way is called "chemoprevention."

Most clinical research that tests a new treatment moves in an orderly series of steps, from early phase I clinical trials to more definitive phase III trials. Each kind of clinical trial asks certain crucial questions.

A phase I trial asks: how does the treatment affect the human body, how should it be given, and what dosage is safe?

A phase II trial asks: does the treatment do what it's supposed to do, and how well does it work?

A phase III trial asks: is the new approach better than current medical practice?

Phase I: What Dosage Is Safe?

In phase I treatment trials, a small number of volunteer patients (usually between 15-30) are given the experimental treatment in gradually larger doses to test for any side effects or complications. The researchers conducting the trial will also try to determine what a safe dose would be and how it should be given.

Laboratory studies during this period also yield information about how the treatment is processed in the body - how the drug or biologic itself changes, which organ systems it affects, how long it stays in the body, and how the body gets rid of it. About 70 percent of drugs tested in phase I trials are successful enough to go on to phase II trials.

Often, cancer patients who decide to participate in phase I trials are no longer benefitting from the standard drugs that are available, or they have a type of cancer for which there is no effective treatment. They may benefit from the treatment they receive in a phase I trial, but the main goal at this early stage is to see how the new treatment affects the body and to determine the right dose and treatment schedule for further testing in phase II studies.

About the Author

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