Expanding Patient Access

Until recently, the use of investigational drugs outside the scope of well-controlled clinical studies was almost nonexistent. Patients who were not eligible for ongoing clinical studies were not given access to some potentially promising drugs that might have made a positive difference in their quality or length of life.

As a result, awareness began to emerge that patients with certain diseases or conditions who were afforded a limited number of, or often no, treatment options or who were unresponsive to all available treatments, would likely be willing to accept much greater risks when being treated if it was possible that they would receive some benefit from the treatment. A recognized need led to the development of a mechanism that would allow these patients access to otherwise unavailable investigational drugs.

In developing a mechanism for patient access to therapy, many issues had to be considered. First, it would be imperative for a physician to recognize the need for treatment with the investigational drug. Second, the physician would have to be willing to accept the responsibility of using an investigational drug and monitoring the patient at closer and more controlled intervals than might be necessary with marketed drugs. Third, to avoid compromising the scientific study of the safety and effectiveness of investigational drugs through well-planned, well-controlled clinical studies, the patient must be deemed ineligible for all ongoing clinical studies with the drug. The result was a compassionate-use exception, granted upon documented justification, for investigational drugs to be used to treat an individual patient. By identifying an individual patient's need, contacting a drug company to confirm availability of the drug, and submitting a case study and other documents to and receiving approval from the Food and Drug Administration (FDA) and the Institutional Review Board (IRB), the physician could treat the patient with the investigational drug. The physician was obligated to become familiar with the investigator's brochure for the product and to report back to the FDA and the drug company sponsor on the results of the treatment.

A few years' experience reviewing and granting compassionate-use exceptions made clear the need for more definitive regulations. It was believed that not all patients were being given the opportunity to receive promising new therapies when their condition could benefit from early treatment. In addition, it was noted that in some cases, after a drug had been demonstrated to be effective and safe in at least one clinical study but was not yet approved by the FDA or in wide distribution, patients with severe diseases who could benefit from treatment with the drug were not being given access to the treatment. The FDA required physicians providing investigational drug access to patients on a compassionate basis to submit separate paperwork for each patient. Each case was then reviewed individually and subject to approval by the FDA before such an allowance could be made.

Recognizing that the process was cumbersome and significantly time consuming, and realizing that patient access to promising therapies could be expanded without compromising the development program of the product, the FDA changed the law to provide for the use of investigational drugs in the treatment of an individual patient or small group of patients in a managed way. The original considerations of physician involvement and patient management remain; however, the way in which permission is received from the FDA is more clearly defined and somewhat different. Three distinct mechanisms exist for treating patients. The first is called the single-patient-use protocol, formerly referred to as the compassionate-use protocol. This protocol may be submitted by an investigator (in the form of an Investigational New Drug Application [IND]) to the FDA to treat between one and five patients (as specified in the protocol). Additional patients may be added to the protocol by filing an amendment to the IND.

The second mechanism is called a treatment protocol. The treatment protocol is a protocol submitted by the study drug sponsor to provide broader access to an investigational product before receiving approval from the FDA to market the product. The protocol typically allows for the treatment of tens to hundreds of patients under the care of any interested physicians who wish to treat patients with the product. Physicians gain participation in the protocol by directly contacting the study drug sponsor and completing a small number of regulatory documents. The necessary documents are then filed by the study drug sponsor as an amendment to their IND.

The third mechanism is called emergency use. This mechanism is used only when no other alternative exists. If an investigator determines that a subject must be provided with an investigational drug immediately (i.e., within 30 days) and the study drug sponsor does not have a treatment protocol open, the investigator may request the investigational drug from the study drug company and may treat the patient with the drug if the following conditions are met:

The patient's condition is severe or life-threatening.

No other treatment option exists for the patient, or all other treatment options have been tried and have failed.

Delay in treatment with the investigational drug could be fatal to the patient.

There is not sufficient time to prepare and submit to the FDA the necessary documents for a single-patient-use protocol.

Notification is provided to the FDA by rapid communication (fax, telephone), indicating the urgency of the request.

The IRB is notified and provides approval of the emergency treatment (approval by the full committee is not required—the committee chairperson may make approvals for emergency treatment, if the institution's procedures so allow).

Within 1 week after the emergency use, the investigator must file documentation to the FDA along with all completed regulatory forms. Emergency-use treatments with an investigational drug must be documented fully and completely and are subject to Good Clinical Practice (GCP) regulations.

These expanded-use protocols not only afford the patient access to promising investigational drugs, they also provide the sponsor with an opportunity to study the drug in a broader population. These studies provide useful data for premarketing surveillance and may serve as a natural transition to the observational surveys that characterize Phase III and Phase IV development.

Along with the decision to proceed with the expanded use of the investiga-tional drug, numerous important issues must be considered, including the issues resulting from the decision itself.

0 0

Post a comment