Questions and Answers about treatment of serious and life threatening illnesses, and use of investigational drugs
Expanded Access to Investigational Drugs
Seriously ill patients often receive significant benefits from drugs that FDA approved for marketing. Sometimes approved drugs have not adequately treated a patient’s illness and they may want to get access to drugs that have not yet cleared the FDA approval process.
The following questions explain how patients may gain access to investigational drugs.
- What is the difference between an approved and an investigational drug?
- What if there is no approved drug, or I have taken an approved drug, and it did not, or has stopped working for me, or if I cannot tolerate the side effects caused by the drug?
- What should I ask if I am interested in participating in a clinical trial?
- How can I find clinical trials that I might be interested in, learn where they are being conducted, and learn more about them?
- What if I cannot find or get into a clinical trial?
- What is expanded access?
- What are the different levels of expanded access and how do they differ?
- Why are there different categories?
- How does FDA evaluate requests for expanded access?
- How are my rights protected?
- How can I find expanded access programs?
1. What is the difference between an approved and an investigational drug?
In general, an approved drug is a drug that has been carefully investigated in some disease or symptomatic condition (headache, for example) to see whether it is effective (helpful) in treating the disease or condition and to define its side effects. Effectiveness is measured by conducting a clinical trial (or study) in people in which the drug is compared with some other treatment, often a placebo, sometimes a treatment known to be effective. A drug is approved when the FDA finds that the studies carried out show that the drug is safe and effective for the treatment of that disease or condition.
Patients who have failed treatment with approved drugs sometimes seek treatment with an unapproved drug that is being studied in the treatment of the patient’s disease or condition. A drug that is being studied in a clinical trial is an “investigational drug.” These are also sometimes referred to as experimental drugs.
Clinical trials and other studies of drugs provide information about:
whether the drug has the desired effect
how much to give (dose) and how often (regimen)
what side effects to look for, so that they can best be managed if they occur
which drug to use, or avoid, in combination when treating multiple conditions, when to take the drug, and how (with food, on an empty stomach, whether to avoid certain foods that might affect blood levels or metabolism of the drug)
how a drug is broken down (metabolized) in the body or excreted, and by what organs (for example, liver, or kidneys)
how long it remains in the body, and at what levels in the blood
Treatment with approved drugs is usually paid for by health insurance plans. Much is known about their safety and effectiveness through the information gained in clinical trials.
2. What if there is no approved drug, or I have taken an approved drug,and it did not, or has stopped working for me, or if I cannot tolerate the side effects caused by the drug?
Sometimes a change in dose can increase drug effect or reduce side effects. Such changes should always be discussed with your healthcare provider. Often, there are many approved drugs available to treat an illness. Your health care provider can guide you to an alternate approved therapy.
However, patients who have exhausted treatment with drugs approved to treat a disease or condition, might obtain access to a drug that is not approved yet by participating in a clinical trial of that drug.
Of course, less is known about an unapproved drug that is being studied in a clinical trial than is known about a drug that is already approved for treatment of that disease, but drugs sometimes have different effects in different people.
While there is no doubt that part of the reason people enroll in trials of unapproved drugs is to gain access to such drugs, it is important to recognize that the main purpose of a clinical trial is to study the drug, not to treat patients.
Clinical trials are
scientific studies to help determine if a drug is safe and effective for a specific illness
usually well-controlled, so that a good comparison can be made with other treatments; this means only a fraction (usually half) of the study subjects will get the experimental drug; the rest will get placebo or an established drug. In most cases, subjects will be “blinded” to treatment (will not know which treatment they are getting)
usually conducted at specific test sites around the country, and not in every community
often run by specific doctors (investigators)
not open to everyone ( there are specific criteria for participation to try to limit complications that might come from testing different people with different medical problems
a possible alternative for patients who have run out of other treatment options
Carefully read information about a drug trial you are considering, and ask questions about exactly what will happen. You are entitled to full information before you decide to enter a trial.
For more information, see Basic Questions and Answers about Clinical Trials
4. How can I find clinical trials that I might be interested in, learn where they are being conducted, and learn more about them?
The Federal Government has created a database of clinical trials for illnesses, available to everyone on the web. Clinicaltrials.gov permits tailored searches by illness, by locality, or other search terms to link patients with appropriate clinical trials.
Sometimes patients who have run out of options for treating their serious illness can get access to an unapproved, investigational drug, for the purpose of treatment, outside of the clinical trial.These are patients with a serious or life-threatening disease and no reasonable treatment alternatives, who, consulting with their healthcare provider, believe that a specific investigational drug might help them. Under certain circumstances, FDA has the authority to permit such patients to be treated with an investigational drug before it is approved and available to the general public through a path known as expanded access. The opportunity to be treated with an unapproved investigational drug under expanded access is dependent upon the ability and willingness of the drug developer to provide the drug.
In other words, FDA has a framework that allows access to investigational drugs outside of a clinical trial, but it is up to the company and the treating doctor to make arrangements to provide and administer the drug.
A company may not always be willing or able to provide drug for expanded access use. For example, a company may not be able to manufacture enough drug to provide access outside of their clinical trial.
Expanded access, sometimes referred to as “compassionate use,” is the use of an investigational drug outside of a clinical trial, for the sole purpose of treating a patient or patients with a serious or life-threatening disease who have no acceptable medical options.
Treatment with an investigational drug via expanded access should not be considered the same as ordinary drug treatment. It is important to remember that the drug is under study to evaluate its safety and effectiveness. Thus, while drugs made available under expanded access may offer therapeutic benefits, they may not. Drugs made available under expanded access may have unknown side effects, some of which may be severe or life-threatening.
Expanded access depends on a number of different factors including:
Whether the patient(s) has a disease that is serious or life-threatening and no treatment options
How much is known about the safe use and dosing of the investigational drug and what possible effects it might have on patients
The patient’s medical history (other medications, other medical complications such as liver or kidney problems, high blood pressure, other illnesses, stage of illness, etc.)
The willingness of the drug’s manufacturer to make the drug for treatment purposes
Whether expanded access could interfere with drug development
There are different levels of expanded access. These are based on the number of patients to be treated and how much is already known about the drug:
Individual patient” access, where access is requested for a single patient
Intermediate-size” group access, where access is requested for a group of patients that is somewhere in size between a single patient and a large group of patients
Access for larger groups of patients through a “treatment IND” or “treatment protocol,” where hundreds to thousands of patients might gain treatment access to an investigational drug through a large scale program.
More evidence is needed of a drug’s safety, and its potential efficacy in the treatment of a disease before allowing larger numbers of patients to be exposed to the investigational drug under an expanded access program. Less evidence is necessary to support use by a single patient, where a detailed medical history is available, and possible medical risks can be assessed for the individual.
FDA medical staff generally consider several major points in evaluating a request:
Activity and toxicity of the drug
Other treatment options
Whether the sponsor is pursuing drug development
Whether treatment use will delay or negatively impact drug development
Whether the patient has a serious or life-threatening disease
Whether the potential benefits of the drug justify the potential risks
Patients seeking treatment use under expanded access must participate in an informed consent process and sign an informed consent document to show they understand any known risks of the drug, that the drug has not yet been shown to be safe and effective, and that there are unknown risks that may be associated with the drug.
All expanded access protocols must be reviewed by an Institutional Review Board (IRB). The IRB is a special local committee responsible for ensuring that the rights and safety of patients using investigational drugs are protected and the patient is aware that there are potential risks.
Patients who seek expanded access to a particular drug must consult with their doctor to discuss whether such use is appropriate to their particular circumstance.
Many (but not all) expanded access programs can be found by using the Search feature at ClinicalTrials.gov. You may also call the company studying the drug to inquire about possible availability outside of clinical trials.
Select “Advanced Search” on the Search Page.
Find the field titled “Study Type” and select “Expanded Access Studies” from the pull-down menu.
(Note: Additional search terms (e.g., condition) may be added to the Advanced Search.)
Select “Search” to see a list of expanded access programs.
Alternatively, you may view a list of all currently available Expanded Access studies.
If a drug isn’t listed, a request can still be made.
The doctor will need to contact both the drug maker to determine whether they are willing and able to make the drug available, and the FDA to determine whether treatment use is allowed to proceed. The company will provide the appropriate contacts at FDA. The doctor will need to provide the FDA with information about the patient's medical history and condition, and the rationale for requesting access to the drug. FDA will need to determine whether the rationale and information provided are sufficient to allow access to the investigational drug. If they are, FDA will permit the company to send the investigational drug to the doctor for the patient.
Physicians should follow the procedures outlined on FDA's page entitled Physician Request for a Single Patient IND for Compassionate or Emergency Use
For additional information, see Final Rules for Expanded Access to Investigational Drugs for Treatment Use and Charging for Investigational Drugs