ANOTHER WAY TO GET A LIFE SAVING DRUG Drug Access and Emergency IND's (C) April 1994. All Rights Reserved. Eugene P. Schonfeld, Ph.D. President and Chief Executive Officer National Kidney Cancer Association 1234 Sherman Avenue Evanston, Illinois 60202 708-332-1051 The Food and Drug Administration (FDA) is charged with regulating food, therapeutics (pharmaceuticals and biologics), vaccines, diagnostic kits, blood supplies, and medical devices. Access to new drugs and therapies is controlled by the FDA through clinical trials leading to formal marketing approval. For several years, patients with life threatening diseases have pushed the U.S. Food and Drug Administration to provide greater access to new treatments. The National Kidney Cancer Association has been a strong advocate of expedited FDA procedures for new cancer treatments and easier patient access to new therapies. During the last half of 1993, the FDA started to respond to the needs of cancer patients. It created two new full time staff positions in the Office of AIDS and Special Health Issues. These positions were filled by Patty Delaney and Ellen Cutler, well qualified FDA employees with prior experience in oncology and public communications. Their assignment is to provide better liaison between the FDA and cancer organizations as well as patients, and to coordinate cancer related activities with the FDA and Public Health Service agencies. Approved Drugs and Clinical Trials Typically, cancer patients are treated with approved therapies or with an Investigational New Drug through a clinical trial. In kidney cancer, interleukin-2 is the only FDA approved treatment for advanced metastatic disease. It is marketed by Chiron Corporation under the tradename Proleukin. Some kidney cancer patients are also treated with drugs which are FDA approved for diseases other than kidney cancer. The most common drug of this type is interferon-alpha which is made by several companies, most notably Schering under the tradename Intron-A. Many patients are also treated with Investigational New Drugs and therapies through clinical trials. It is not uncommon to see kidney cancer patients in trials treated with IL-4, IL-6, gamma interferon, GM-CSF, and other agents. Before these products enter human clinical trials, they have been researched with laboratory tests and in animals. They have not yet been approved by the FDA for general marketing, however, they have demonstrated enough efficacy and safety to justify warrant use in clinical trials. Emergency IND's Patients who are not eligible for clinical trials may be eligible to receive drugs and therapies which are not yet FDA approved by having their doctor apply to the FDA for an Emergency IND (Investigational New Drug). Many patients and physicians may not be familiar with the process of applying for an Emergency IND. But it really is quite simple and may be extremely useful in the care of patients. Who? An Emergency IND starts with a single patient and a single doctor. The doctor makes a request to the FDA for an Emergency IND and proposes a course of treatment. If the Emergency IND is granted, it authorizes the doctor to treat the patient with a drug or therapy which is not yet FDA approved. In the case of a cancer drug or therapy, the physician can contact Ellen Cutler at the FDA by calling 301-443-0104. The physician will be directed to the appropriate division within the FDA where the request for an Emergency IND will be reviewed. When? Seeking an Emergency IND is especially appropriate under the following circumstances: (1) when the patient is no longer responding to approved therapies and no other adequate treatment is available; (2) when a patient is not eligible for a clinical trial but would be an appropriate candidate for treatment with a drug that is being tested in a clinical trial; (3) when the most appropriate drug or therapy for the patient is not currently available through a clinical trial (i.e. a drug that was tested in a clinical trial but is no longer available); and (4) when a promising drug has been through pre- clinical testing but has not yet entered into human clinical trials. One or more of these conditions may indicate that it is appropriate to seek an Emergency IND for a patient. In making a request, it is always important (1) to state those conditions which support the request and (2) to submit information which supports the proposed course of treatment. For example, a doctor can submit a medical journal article on the drug and protocol. For a drug or therapy not yet tested clinically, a doctor must submit pre-clinical animal research data, toxicity data and manufacturing information assuring the identity, quality, purity, and strength of the drug (e.g. a certificate of analysis). What is Submitted? The physician needs to submit information to the FDA review division so the agency can make an informed decision and assess the appropriateness of the request. This information includes: (1) The name of the drug and the indication for which it is being sought. A statement regarding the supplier of the drug (source of the drug, such as the drug company which makes it or the NCI which distributes it.) (2) The medical history of the patient for which the drug or therapy is intended. This history should include information on any prior therapy and response, and the rationale for the proposed treatment. The rationale may be strengthened by including any research information on the patient's tumor, such as results of an in vitro drug test with the proposed agent on the patient's tumor. (3) The protocol detailing the proposed treatment plan (dose, route of administration, and duration). The doctor should also include procedures for monitoring the patient and planned modifications in the event of intolerable toxicity or unforeseen side effects. (4) A statement that informed consent will be obtained prior to initiating treatment. The application should include a copy of the consent form which has been drafted for the patient's signature, or signed by the patient. (5) A statement of the physician's qualifications as an investigator should be included. A copy of his or her curriculum vita is sufficient. (6) If the physician has obtained approval of the IRB (Institutional Review Board) at his institution, a statement to that effect should be included with the application. At the very least, a statement should be included that the IRB will be advised of the treatment within five days. The completed application for an Emergency IND can be FAXed to the appropriate FDA division. FDA Response The FDA recognizes that a request for an Emergency IND is urgent and the agency will try to respond as quickly as possible. Typical response time is 24 to 48 hours, and same day approvals are not uncommon, particularly when the request is well documented and complete. If the FDA approves the application, response is made by letter acknowledging the issuance of the IND number with instructions on how to complete the process. Someone from the FDA will call the physician directly and will verbally provide the IND number. Physician Response The physician then calls the supplier of the drug or therapy, provides the IND number, and the drug is shipped, usually by express shipping service. The physician then treats the patient according to his plan. As part of the process, upon receipt of the FDA letter, the physician is required to fill out FDA Form 1571 and provide a complete copy of the original correspondence. When treatment is completed, the physician should submit the results of treatment to the FDA and request withdrawal of the IND. In some cases, when treatment is extended, the physician is required to submit an annual report on the patient's progress. Some suppliers also request a follow up report in return for providing the drug. Regulatory Restraints Clinical investigators' responsibilities when using investigational drugs are well defined by FDA regulations (21 CFR Part 312), including: (1) use of the drug or therapy only in accordance with the treatment plan submitted; (2) use of the drug or therapy only in the named patient under the doctor's personal supervision or under the supervision of other investigators who are responsible to him or her; (3) assurance that an IRB reviews or approves the study; and (4) obtaining proper informed consent from the patient or from his or her legal representative. Under the regulations, the physician is precluded from: (1) giving the drug to another physician not responsible to him or her, (2) giving the drug to patients other than the one named in the application, and (3) giving the drug to a physician in another institution for use on his or her patients. Limitations The Emergency IND is a very special application because its relates to an individual patient who is confronting an immediate medical crisis. Hopefully, treatment under the Emergency IND will be successful. However, even if the IND is granted and treatment proves successful, the company producing the drug or therapy may not find the results useful. When a physician provides a new drug or therapy in an emergency situation, the protocol may be tailored to the specific patient. It may not be applicable to the overall population of patients with the same disease. Other Benefits When used appropriately, the Emergency IND can benefit patients and advance the development of new drugs and therapies, particularly if information from the Emergency IND makes its way into the scientific community as well as back to companies and the FDA. Patients, physicians, researchers, companies, and the FDA itself should give careful consideration to using Emergency IND's. These applications are useful tools which can help individual patients and provide insights which help all patients. Get In Touch For more information, contact: Ellen Cutler, Food and Drug Administration HF- 12, Parklawn Building Room 12A40, 5600 Fishers Lane, Rockville, MD 20857, 301- 443-0104, FAX 301-594-6807.