Sunday, 9 October 2011

Expanded access program (EAP)

Title 21 part 313.34 of the Code of Federal Regulations provides for use of unapproved drugs to treat patients with serious or immediately life-threatening diseases ineligible for clinical trials and without available alternative therapy. EAPs can provide drugs to individual patients under "single patient Investigational New Drug (IND)" and to larger numbers under "treatment IND". The criteria for drug use under "Treatment IND" include a life threatening disease, no other treatments available, preliminary evidence of efficacy, ongoing or completed definitive clinical trials, marketing approval has been pursued, and absence of interference with the registration process. EAPs are implemented while sponsors are actively pursuing marketing approval. Reasonable evidence of clinical usefulness for the indication and sufficient safety information from ongoing or completed trials are required. EAPs are voluntarily initiated by the drug sponsor. FDA and IRB approvals and safety monitoring are required. EAPS can be used for a widerange of diseasesincluding AIDS,cancer,rare diseases and cardiovascular diseases.

Medical professionals use the term "compassionate use" to refer to the treatment of a seriously ill patient using a new, unapproved drug when no other treatments are available. Drugs that are being scientifically tested but have not yet been approved by the US Food and Drug Administration (FDA) are called investigational drugs. Being able to use one of these drugs when you are not in a clinical trial has many names, but is most commonly referred to as compassionate use.

Since 1987, the FDA has had rules in place that have enabled patients, under specific circumstances, to access drugs or biologics that are still in development for treatment purposes. These expanded access program rules were amended in 2009 by the FDA.

The regulations include the following:

Criteria that must be met in order to authorize the expanded access use
Requirements for expanded access submissions
Safeguards to protect patients and the clinical trial process

The regulations also include general criteria for granting expanded access:

The patient must have a serious condition or disease for which there is no comparable alternative therapy available
The patient must be unable to participate in a clinical trial
The potential benefit must outweigh the potential risk of using the treatment
The drug manufacturer or supplier must agree to provide the drug and necessary supporting regulatory information
An Institutional Review Board (IRB) must approve the treatment plan
There should be no impact on the completion of a clinical trial

EAPs can provide drugs to individual patients under "single patient Investigational New Drug (IND)" and to larger numbers under "treatment IND".

Expanded access

A company sponsoring a drug in the late stages of drug development, such as Phase III clinical trials, can offer expanded access programs for patients who are not able to enroll in a clinical trial. The FDA generally approves these EAPs if the drug has shown that it works at least somewhat to treat a specific disease in the clinical trials that are being done.

Single patient access
Patients who don’t qualify for either clinical trials or an expanded access program (if one exists) may be able to get the unapproved new drug by applying for single patient access.

In this case, the patient’s doctor must first ask the drug company if the drug can be used for the patient and see if the drug company will supply it. If the company agrees, the patient’s doctor works with the drug company to ask the FDA to approve the drug for use by this one patient.

The FDA requires the doctor to send information about the patient, why the request is being made, the proposed treatment plan, and a signed informed consent from the patient.The length of time it takes to get single patient access varies. But if it is an emergency, the FDA can complete the paperwork in 24 hours.

Before a patient or group of patients is allowed to have access to an unapproved, new drug outside of a clinical trial two things MUST be in place:

The owner (sometimes referred to as the sponsor, generally a drug company) of the new, unapproved drug must agree to allow the use of their drug outside of the clinical trial, and
The FDA medical officer in charge of the regulatory oversight of that new drug's development must concur before the patient or patients may begin taking the drug.

Many drug companies refuse compassionate use requests. Reasons for refusal may include:

Lack of efficacy - there may be little evidence that the drug may be effective for the specific illness
Safety - the drug may have toxicity problems which aren't public knowledge.
Cost - compassionate use can be expensive, especially large access programs
Production capacity - drugs can be expensive and time-consuming to make, and until approved, capacity to manufacture the drugs may be limited
Priorities - companies may want to use 'left-over' drugs for clinical trials in different illnesses
It is important to remember that drug companies are not required to provide their unapproved drug to patients outside of a clinical trial and under no circumstances can a drug company be compelled to do so. The FDA generally supports requests for compassionate use if the patient has exhausted standard treatment options and is ineligible for clinical trials. However, if the FDA is aware of safety issues that may foreshorten a patient's life the FDA may refuse the patient's application. This is a rare occurrence.

In brief an expanded access program is a way of making an investigational drug (unapproved drugs) available to patients without other treatment options, once basic requirements for safety and efficacy have been established, prior to the registration and governmental approval of a new drug by the U.S. Food and Drug Administration (FDA). Patients who participate in expanded access programs have previously exhausted the benefits of approved therapies.

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