1. What is an investigational drug?

An investigational drug is one that is under study but does not have permission from the U.S. Food and Drug Administration (FDA) to be legally marketed and sold in the United States.

FDA approval is the final step in the process of drug development. The first step is for the new drug to be tested in the laboratory. If the results are promising, the drug company or sponsor must apply for FDA approval to test the drug in people. This is called an Investigational New Drug (IND) Application. Once the IND is approved, clinical trials can begin. Clinical trials are research studies to determine the safety and measure the effectiveness of the drug in people. Once clinical trials are completed, the sponsor submits the study results in a New Drug Application (NDA) or Biologics License Application (BLA) to the FDA. This application is carefully reviewed and, if the drug is found to be reasonably safe and effective, it is approved.

2. How do patients get investigational drugs?

By far, the most common way that patients get investigational drugs is by taking part in a clinical trial sponsored under an IND. A patient’s doctor may suggest a clinical trial as one treatment option. Or a patient or family member can ask the doctor about clinical trials or new drugs available for cancer treatment.

Another way patients and their families can learn about new drugs being tested in clinical trials is through the National Cancer Institute’s (NCI) PDQ® database. This database contains information on a large number of ongoing studies. Individuals can search this database at http://www.cancer.gov/clinicaltrials, or they can call the NCI’s Cancer Information Service at 1–800–4–CANCER (1–800–422–6237). Information specialists can search the database and provide a list of trials for individuals to discuss with their doctor.

3. Are there other ways to get investigational drugs?

Less common ways that patients can receive investigational drugs include mechanisms such as an expanded access protocol or a special or compassionate exception. The sponsor must agree to provide the drug for this use.

Investigational drugs given under these mechanisms must meet the following criteria:

• There must be substantial clinical evidence that the drug may benefit persons with particular types of cancer.
• The drug must be able to be given safely outside a clinical trial.
• The drug must be in sufficient supply for ongoing and planned clinical trials.

Expanded Access
The purpose of an expanded access protocol is to make investigational drugs that have significant activity against specific cancers available to patients before the FDA approval process has been completed. Expanded access protocols allow a larger group of people to be treated with the drug.

The sponsor must apply to the FDA to make the drug available through an expanded access protocol. There must be enough evidence from studies already completed to show that the drug is likely to be effective against a specific type of cancer and that it does not have unreasonable risks. The FDA generally approves expanded access only if there are no other satisfactory treatments available for the disease.

The NCI’s Treatment Referral Center (TRC) protocols are one type of expanded access protocol. The NCI establishes a TRC protocol when clinical evidence suggests that an investigational drug should be made more widely available to patients, even though the FDA approval process has not been completed. The TRC protocol is made available at NCI-designated cancer centers and other institutions selected to provide wide geographic availability of the drug to patients.

Special Exception/Compassionate Exemption
Patients who do not meet the eligibility criteria for a clinical trial of an investigational drug may be eligible to receive the drug under a mechanism known as a special exception or a compassionate exemption to the policy of administering investigational drugs only in a clinical trial. The patient’s doctor contacts the sponsor of the investigational agent and provides the patient’s medical information and treatment history. The sponsor (the drug company or NCI) evaluates the requests on a case-by-case basis. There should be reasonable expectation that the drug will prolong survival or improve quality of life.

In some cases, even patients who qualify for treatment with an investigational drug on a compassionate basis might not be able to obtain the drug if the supply is limited and the demand is high.

4. Are all investigational drugs available through an expanded access or special exception mechanism?

No. The sponsor decides whether to provide an investigational drug outside a clinical trial. Availability may be limited in part by drug supply, patient demand, or other factors.

5. What is the NCI’s role in providing access to investigational drugs?

The NCI acts as the sponsor for many, but not all, investigational drugs. When acting as sponsor, the NCI provides the investigational drug to the physicians who are participating in clinical trials or TRC protocols. A physician who wishes to treat a patient with the investigational drug as a special exception must request the drug from the NCI. These requests are reviewed on a case-by-case basis.

6. Who can provide access to investigational drugs being developed by pharmaceutical companies?

In the case of investigational drugs sponsored by a drug company, the drug company in collaboration with the FDA provides access to the drug. The process is similar to that described above.

The patient’s physician must submit a request to the drug company and to the FDA. The drug company can provide the name of the appropriate reviewing division at the FDA. (FDA reviewing divisions are prohibited from divulging proprietary information such as whether a sponsor has filed an IND or the status of an IND.)

7. Are there specific criteria used to determine whether patients can receive an investigational drug outside a clinical trial?

To be considered for treatment with an investigational drug outside a clinical trial, generally patients must meet the following criteria:

• Have undergone standard treatment that has not been successful.
• Be ineligible for any ongoing clinical trials of this drug.
• Have no acceptable treatment alternatives.
• Have a cancer diagnosis for which the investigational drug has demonstrated activity.
• Be likely to experience benefits that outweigh the risks involved.
  
  
8. What should patients do if they are interested in receiving an investigational drug through a special exception or expanded access mechanism?

Patients interested in gaining access to investigational drugs should talk to their physician about available options. Physicians can make requests for special exceptions by contacting the study sponsor. Physicians will be required to follow strict guidelines, including gaining approval from their Institutional Review Board and obtaining informed consent from the patient. Informed consent is a process that includes a document to be signed by the patient which outlines the known risks and benefits of the treatment, as well as the rights and responsibilities of the patient.

9. What are the costs involved in receiving an investigational drug?

In general, the drug is provided free of charge. However, there may be other costs associated with the treatment. Before beginning treatment, patients should check with their insurer about coverage of these costs.

10. What are some of the potential drawbacks to receiving an investigational drug?

It is not known whether an investigational drug is better than standard therapy for treating a disease, and a patient may not receive any benefit. Side effects (both long-term and short-term) from the drug may not be fully understood, especially if the drug is in early phases of testing. Finally, a patient’s health insurance company may not pay expenses associated with receiving the investigational drug.

11. How can patients find out more information about a specific investigational drug?

Patients can find out more about a specific drug by contacting the drug company that is developing the drug. Information may also be available from the NCI’s Cancer Information Service at 1–800–4–CANCER (1–800–422–6237).

12. What other resources are available on this topic?

The following list of resources may be helpful:

• The NCI’s Web site has a feature titled Understanding the Approval Process for New Cancer Treatments: Special Needs, which can be found at http://www.cancer.gov/clinicaltrials/learning/approval-process-for-cancer-drugs/page4 on the Internet.
  
  
• Another NCI Web site is the Drug Development and Approval home page, which can be found at http://www.cancer.gov/cancertopics/treatment/druginformation on the Internet.

# # #

• National Cancer Institute Fact Sheet 1.4, NCI’s Clinical Trials Cooperative Group Program ¹ (http://www.cancer.gov/cancertopics/factsheet/NCI/clinical-trials-cooperative-group)
• National Cancer Institute Fact Sheet 1.17, The NCI/VA Agreement on Clinical Trials: Questions and Answers ² (http://www.cancer.gov/cancertopics/factsheet/NCI/VA-clinical-trials)
• National Cancer Institute Fact Sheet 1.22, Cancer Clinical Trials at the National Institutes of Health Clinical Center: Questions and Answers ³ (http://www.cancer.gov/cancertopics/factsheet/NCI/clinical-center)
• National Cancer Institute Fact Sheet 2.11, Clinical Trials ⁴
  (http://www.cancer.gov/cancertopics/factsheet/Information/clinical-trials)
• National Cancer Institute Fact Sheet 8.14, More Choices in Cancer Care: Information for Beneficiaries on Medicare Coverage of Cancer Clinical Trials ⁵
  (http://www.cancer.gov/cancertopics/factsheet/support/medicare)
• If You Have Cancer and Have Medicare … You Should Know About Clinical Trials ⁶ (http://www.cancer.gov/clinicaltrials/resources/medicare-and-cancer-trials)
• Taking Part in Cancer Treatment Research Studies ⁷ (http://www.cancer.gov/clinicaltrials/Taking-Part-in-Cancer-Treatment-Research-Studies)

How can we help?

We offer comprehensive research-based information for patients and their families, health professionals, cancer researchers, advocates, and the public.

• Call NCI’s Cancer Information Service at 1–800–4–CANCER (1–800–422–6237)
• Visit us at http://www.cancer.gov or http://www.cancer.gov/espanol
• Chat using LiveHelp, NCI’s instant messaging service, at http://www.cancer.gov/livehelp
• E-mail us at cancergovstaff@mail.nih.gov
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Glossary Terms

A term for diseases in which abnormal cells divide without control and can invade nearby tissues. Cancer cells can also spread to other parts of the body through the blood and lymph systems. There are several main types of cancer. Carcinoma is a cancer that begins in the skin or in tissues that line or cover internal organs. Sarcoma is a cancer that begins in bone, cartilage, fat, muscle, blood vessels, or other connective or supportive tissue. Leukemia is a cancer that starts in blood-forming tissue such as the bone marrow, and causes large numbers of abnormal blood cells to be produced and enter the blood. Lymphoma and multiple myeloma are cancers that begin in the cells of the immune system. Central nervous system cancers are cancers that begin in the tissues of the brain and spinal cord. Also called malignancy.

Having to do with the examination and treatment of patients.

A type of research study that tests how well new medical approaches work in people. These studies test new methods of screening, prevention, diagnosis, or treatment of a disease. Also called clinical study.

The process of identifying a disease, such as cancer, from its signs and symptoms.

In clinical trials, requirements that must be met for an individual to be included in a study. These requirements help make sure that patients in a trial are similar to each other in terms of specific factors such as age, type and stage of cancer, general health, and previous treatment. When all participants meet the same eligibility criteria, it gives researchers greater confidence that results of the study are caused by the intervention being tested and not by other factors.

An agency in the U.S. federal government whose mission is to protect public health by making sure that food, cosmetics, and nutritional supplements are safe to use and truthfully labeled. The Food and Drug Administration also makes sure that drugs, medical devices, and equipment are safe and effective, and that blood for transfusions and transplant tissue are safe. Also called FDA.

A process in which a person is given important facts about a medical procedure or treatment, a clinical trial, or genetic testing before deciding whether or not to participate. It also includes informing the patient when there is new information that may affect his or her decision to continue. Informed consent includes information about the possible risks, benefits, and limits of the procedure, treatment, trial, or genetic testing.

A group of scientists, doctors, clergy, and consumers that reviews and approves the action plan for every clinical trial. There is an Institutional Review Board at every health care facility that does clinical research. Institutional Review Boards are designed to protect the people who take part in a clinical trial. Institutional Review Boards check to see that the trial is well designed, legal, ethical, does not involve unneccesary risks, and includes safeguards for patients. Also called IRB.

A substance that has been tested in a laboratory and has gotten approval from the U.S. Food and Drug Administration (FDA) to be tested in people. An investigational agent may be approved by the FDA for use in one disease or condition but be considered investigational in other diseases or conditions. Also called experimental drug and investigational drug.

A substance that has been tested in a laboratory and has gotten approval from the U.S. Food and Drug Administration (FDA) to be tested in people. An investigational drug may be approved by the FDA for use in one disease or condition but be considered investigational in other diseases or conditions. Also called experimental drug and investigational agent.

PDQ is an online database developed and maintained by the National Cancer Institute. Designed to make the most current, credible, and accurate cancer information available to health professionals and the public, PDQ contains peer-reviewed summaries on cancer treatment, screening, prevention, genetics, complementary and alternative medicine, and supportive care; a registry of cancer clinical trials from around the world; and directories of physicians, professionals who provide genetics services, and organizations that provide cancer care. Most of this information, and more specific information about PDQ, can be found on the NCI's Web site at http://www.cancer.gov/cancertopics/pdq. Also called Physician Data Query.

Medical doctor.

A detailed plan of a scientific or medical experiment, treatment, or procedure. In clinical trials, it states what the study will do, how it will be done, and why it is being done. It explains how many people will be in the study, who is eligible to take part in it, what study drugs or other interventions will be given, what tests will be done and how often, and what information will be collected.

The overall enjoyment of life. Many clinical trials assess the effects of cancer and its treatment on the quality of life. These studies measure aspects of an individual’s sense of well-being and ability to carry out various activities.

A problem that occurs when treatment affects healthy tissues or organs. Some common side effects of cancer treatment are fatigue, pain, nausea, vomiting, decreased blood cell counts, hair loss, and mouth sores.

In statistics, describes a mathematical measure of difference between groups. The difference is said to be significant if it is greater than what might be expected to happen by chance alone. Also called statistically significant.

In medicine, treatment that experts agree is appropriate, accepted, and widely used. Health care providers are obligated to provide patients with standard therapy. Also called best practice and standard of care.