Those benefits—and in some countries, the possibility of generating revenue—can make it well worth a sponsor's while to consider EAPs for certain products.

Making the drug available on a global scale can multiply those benefits across a wider marketplace, but the process can be challenging because of differences in regulations and philosophy from one country to the next, particularly in Europe. A thorough understanding of those variations can facilitate a successful global EAP. Such insight is especially important given that the programs are conducted under regulatory review.

Making the Case

EAPs—sometimes called compassionate use programs—have been most commonly used in oncology and HIV/AIDS, although their application is expanding into such areas as neuropathy, hepatitis B, sepsis, and coagulopathy (a disease affecting blood coagulation).

Pharmaceutical companies should consider EAPs when they are developing a new product for a life-threatening illness or disorder that leads to major disability and when there are patients who have exhausted alternative therapies in that particular therapeutic category. However, the decision must be weighed carefully. Regulatory agencies are particularly sensitive to demonstration of patient need. Programs that the agencies perceive to have marketing value only will not be approved.

EAPs are usually established during Phase III of development, between pivotal trials for approval and receipt of marketing authorization. At that point, the sponsor has accumulated sufficient safety and efficacy information to permit use of the new drug in a minimally controlled outpatient setting.

Patient entry criteria for EAPs need not be as strict as they are for clinical trials but should match the indications in the proposed drug label. Patients who participate in an EAP often have not been eligible for a Phase III trial because of co-morbidity, disease stage, or concomitant medication use—or simply because they reside in countries where no clinical trial is available. In the United States, where EAPs are administered primarily through an FDA–designated Treatment Investigational New Drug (IND), a clinician must still determine patient eligibility, but the inclusion/exclusion criteria are more open.

How They Differ

In certain countries, particularly the United States, an EAP is similar to a standard Phase IIIb trial: both are conducted according to a specific protocol and require Institutional Review Board (IRB) oversight and informed consent from patients. The major difference between an EAP and a standard Phase IIIb clinical trial is that no efficacy data are collected. Data collection for an EAP is usually limited to demographic and safety information and involves far fewer case report forms (CRFs). Data monitoring can be done remotely instead of performing on-site visits for source data verification.

In other countries, EAPs can be administered through open-label Phase III trials, cohort patient programs, or named-patient programs. In those capacities, it is the pharmaceutical company's primary role to supply the drug, and it is the physician's responsibility (and decision) to enroll patients.

Unlike a standard clinical trial, an EAP involves an unknown number of patients and sites—which can make it a challenge to plan for adequate production of drug supply, especially before the product has been fully commercialized. Inadequate supply in the face of high demand could adversely affect the good will the company hopes to generate.

Another potentially significant area of difference is medication cost. In Phase III trials, the sponsor provides the medication. In certain types of EAPs, in countries such as France or the United Kingdom (but not typically in the United States), the treatment cost may be covered by a national or private insurance system, and the manufacturer has the option to charge a fee for the drug. Charging payers for the product enables the company to recover some manufacturing, research, development, and handling costs, particularly in the case of new biotechnology products.