This article is the second part of a two-part series on drug development and approval. For an introduction to this subject,  read Drug Development and Approval (Part I).

Speeding up the development and approval process

The U.S. Food and Drug Administration (FDA) is improving the drug development and approval process in several ways.

Facilitating approval of foreign drugs. Each country has a drug regulatory agency with its own set of approval requirements. Even though a drug may be approved in Europe or Japan, it cannot be used in the United States without FDA approval. The International Conference on Harmonization (ICH) is a cooperative effort among the drug regulatory agencies of Europe, Japan, and the United States. The ICH works to make sure that the information required for drug approval decisions is similar between countries. Thus, a sponsor who developed a drug for use in Japan or Europe can submit the same research to the FDA and possibly gain approval for its drug in the United States without having to conduct additional studies.

Fast track programs. The purpose of the FDA's fast track drug development programs is to facilitate the development and expedite the review of drugs that have the potential to address an unmet medical need for serious or life-threatening diseases, like cancer. An unmet medical need exists when there is no available therapy or when a disease or condition is not adequately treated by an existing therapy. Based on these criteria, drug sponsors may request fast track designation for a new drug. If the designation is granted, the drug may be considered for a fast track program, which could result in accelerated approval.

Accelerated approval. The FDA's accelerated approval program provides a means for sponsors to request approval based on alternate findings, otherwise known as surrogate endpoints. Surrogate endpoints are indirect measures of disease status, such as an improvement in disease-related symptoms or a change in laboratory results. These endpoints may also help predict the effectiveness of the therapy. An accelerated approval program allows drugs for serious and life-threatening conditions to be reviewed and brought to market in an expedited manner to address an unmet medical need.

Early interactions with drug sponsors

The FDA is also trying to shorten the time it takes drug sponsors to develop new drugs by working with sponsors earlier in the development process. The goal of this effort is to expedite the development, evaluation, and marketing of new therapies. This is accomplished by conducting meetings between the FDA and the sponsor at several points during the development process to ensure agreement on the appropriate design of clinical studies and timely review of the resulting data.

Orphan drugs

Orphan drugs are therapies that treat rare diseases or conditions that affect fewer than 200,000 Americans. Because such a small number of patients will have a need for these drugs, the drug's sponsor may not recover the costs incurred to develop the drug. The Orphan Drug Act provides incentives for sponsors to develop new drugs to treat rare diseases, including many types of cancer.

Getting drugs to patients who need them

Drugs under study that have not been approved by the FDA are considered investigational drugs. These drugs are usually only available to patients enrolled in clinical trials. After completion of the clinical trials, the FDA may approve a drug if the benefit from taking the drug is determined to be greater than the risk from possible side effects. Recognizing that people who have tried all of the available treatments may be willing to accept a higher level of risk, the FDA has developed the following three programs to make investigational drugs available to people with cancer and other serious illnesses:

Special exception/compassionate exemption. The best way to gain access to investigational drugs is to enroll in a clinical trial, but clinical trials have eligibility criteria (strict rules) that determine if a trial is appropriate for a patient. If the trial is not appropriate, then he or she may be eligible to receive the investigational drug under a special exception/compassionate exemption. The patient's doctor and the drug's sponsor must submit the exception request to the FDA, which reviews applications on a case-by-case basis.

Treatment INDs. The FDA's treatment Investigational New Drug (treatment IND) allows sponsors to request that an investigational drug be provided to patients who are not eligible for clinical trials and for whom there are no satisfactory alternative treatments. There must be sufficient data available to show that the drug may be effective and has not been found to have unreasonable risks.

Group C drugs. The Group C program is an agreement between the FDA and the National Cancer Institute (NCI) to distribute to oncologists investigational drugs that would otherwise be available only through participation in an NCI protocol. The drugs are usually being studied in a phase III trial and have shown evidence of effectiveness in a specific tumor type. Through this mechanism, patients who are not enrolled in clinical trials may still be able to gain access to a potentially effective treatment after informed consent has been obtained.

Off-label use

When the FDA approves a new drug, it means that the drug is approved for treating a specific condition when administered in the manner indicated on the drug's label. Additional clinical research studies may be performed to study other possible indications for the drug's use, such as to treat another type of cancer. If a doctor prescribes an FDA-approved drug to treat conditions not listed on the label or in a manner different from what is indicated on the label, it is referred to as an off-label use of the drug. Off-label drug use in cancer treatment is common for many reasons. First, drugs are generally approved for treating only a particular type or stage of cancer. After approval, a drug that is effective in treating one type of cancer is often found to be effective in treating other types of cancer. Second, many cancer treatments involve a combination of multiple drugs. In this setting, one or more of the drugs is often being used off label. Multiple drug regimens are also constantly changing, as doctors study new combinations to improve patient care.

Approval by the FDA for new labeling information

To gain FDA approval of new labeling information for an already-approved drug, the sponsor must submit a supplemental marketing application to the FDA to establish the safety and effectiveness of the product for the new indication. In some cases, a sponsor may discover that the data required to submit a supplemental application may not be as extensive as that needed for initial approval. The FDA has developed many initiatives to encourage supplemental applications for products used in cancer treatment. For example, the FDA has surveyed private, academic, and professional groups involved in cancer research and treatment to obtain their views regarding off-label drug use and then met with drug sponsors to facilitate submission of a supplemental application.

Patient involvement

One of the best ways for patients to get involved in the drug development and approval process is to participate in a clinical trial. Not only does participation in a clinical trial contribute to the advancement of cancer treatment, patients enrolled in cancer clinical trials receive closely monitored care and frequent assessment of their disease status. The FDA has started two programs to include patients in the development and approval process.

The Cancer Drug Development Patient Consultant Program is designed to include the perspective of patient advocates in the drug development process. Patient advocates selected for the program will participate in meetings (via phone) with the FDA and drug companies to discuss various aspects of the drug development process.

The Patient Representative Program allows a person with cancer to be considered for participation in advisory committee meetings as a patient representative. The role of the patient representative is to provide insight on issues, problems, and/or questions important to the viewpoint of patients and family members. The patient representative must meet several qualifications, and voting members must be appointed as special government employees. Learn more about the FDA's patient participation programs.

Additional Resources

Access to Investigational Drugs: Questions and Answers

Understanding the Approval Process for New Cancer Drugs: Special Needs

Access to Unapproved Drugs

For more information on off-label drug use, including a list of states with laws requiring coverage of off-label drugs, read Understanding the Approval Process for New Cancer Drugs: Q&A: Off-Label Drugs.

For lists of FDA-approved cancer drugs, read Approved Oncology Drugs.

Last Updated: May 08, 2006