Understanding Expanded Access, Compassionate Use and Similar Terms

Patients with a serious disease or condition who have run out of satisfactory treatment options and cannot enroll in a Clinical Trial are considered to have an unmet medical need. They may be interested in learning about the possibility of accessing drugs in development. This is a complex field that is made even more confusing by the lack of consistency in the use of terminology.

There are many different terms used to describe the process of accessing drugs before they are approved in a specific country. To better understand this, it helps to know some of the commonly used terms as well as some underlying principles.

Investigational drugs, often referred to as Investigational Medicinal Products (IMP) by the pharmaceutical industry, are drugs that have not yet been approved by regulatory authorities, such as the U.S. Food and Drug Administration (FDA) or the European Medicines Agency (EMA). Patients with an unmet medical need may be able to access these drugs through Clinical Trials or through mechanisms and programs that allow for exceptional (temporary) use of investigational or experimental drugs, i.e. pre-approval access.

Terminology for describing pre-approval mechanisms or programs may vary by country or even by drug manufacturer. They include: Managed Access Program (MAP), Expanded Access Program (EAP), Named Patient Supply (NPS), Compassionate Use Program (CUP), and many others.

The pharmaceutical industry, as well as patients and treating physicians, are confronted with the fact that the terminology is inconsistent, and the process of getting approvals for access in countries around the world can be confusing and vary widely. That being said, the general purpose of the processes is more or less the same. They involve the delivery of an investigational drug to patients who cannot afford to wait for the completion of a potentially lengthy development and approval process in the country where they reside.

Understanding international differences in accessing investigational drugs

Some countries may have regulations that mandate a drug be approved in at least one other country before pre-approval access will be considered. A large part of drug development today happens in the United States. As a result, most newly developed drugs are initially not approved in countries other than the U.S. Non-U.S. countries therefore need a regulatory mechanism to bridge the gap between approval in the U.S. and approval locally. The reason is that until such time, newly approved drugs are still considered investigational drugs outside of the U.S.

Once a drug is approved in at least one other country, other countries will often allow the drug to be imported for a patient with an unmet medical need. This is allowed as long as the patient:

• Meets the conditions outlined in the country’s specific pre-approval access regulations.
• Fulfills eligibility criteria for the pre-approval access program and a physician is willing to prescribe the drug.

One of the terms used to describe such programs, and adopted early on by the pharmaceutical industry, has been Managed Access Programs (MAP). It was used as an umbrella term to describe a global program that includes several countries and different regulatory pathways. This offered drug developers a way to efficiently provide patients with an unmet medical need and for whom there were no available alternative access routes, access to investigational or experimental medicinal drugs not yet approved and commercially unavailable. They typically make distinctions between the designation “Named patient” for provision to an individual patient and “Cohort” for a group of patients.

In the U.S., the FDA refers to pre-approval access as “Expanded Access” and currently facilitates pre-approval access via Expanded Access regulations in existence since 2009. For an individual patient, the physician requests the drug and is responsible for patient treatment and associated regulatory and program requirements. In the case of intermediate and larger-size programs, the drug developer assumes wider regulatory and program responsibilities.

In Europe, reference is also often made to the names of the frameworks through which the process of obtaining pre-approval access is run. The French Temporary Authorization for Use (ATU) program and the United Kingdom’s Early Access to Medicines Scheme (EAMS) are considered to be two of the better-structured mechanisms to access. In addition to facilitating access for patients with an unmet medical need, both frameworks make provisions for the collection of data that may be used in the regulatory decision-making process rather than simply relying on overseas regulatory approval (U.S. mainly).

Other countries, now establishing their Expanded Access frameworks are looking to the already established models, such as EAMS and ATU, for guidance.

Confusing Terms: Expanded Access, Compassionate Use, Right to Try?

As previously mentioned, current FDA regulations use the term Expanded Access. Unfortunately, there has been a lack of consistency over the years, as the terms Compassionate Use and Expanded Access are used interchangeably. There are even instances where the term EAP Clinical Trial is used because of the similarities that exist between these two distinct pre-approval access pathways. This practice runs the risk of confusing a great number of patients. It is preferable that the term Expanded Access alone be used.

The term Compassionate Use is still frequently used by the media to describe the process of patients accessing an investigational drug outside of a Clinical Trial. Opponents of this term assert that having the word “compassion” embedded in the term is problematic as this should not be the primary motivator for providing a drug. However, one should consider that this term has historically had precedence. For example, during the AIDS crisis, the term Compassionate Use was widely used. It was also used by the cancer patient advocacy movement when it began to emerge in the early 1980s.

Complaints that the FDA’s Expanded Access Program was too burdensome for treating physicians as well as a perceived lack of progress and frustration, led certain groups of patients and a libertarian think-tank called the Goldwater Institute to initiate the Right to Try movement. This captured the public’s attention at the time and has muddied the waters ever since. The movement led to a federal law known as the Right to Try Act. It created an alternative pathway for patients in the United States to access investigational drugs, outside of the FDA’s Expanded Access regulation. Reference is often mistakenly made to Right to Try when in fact, pre-approval within the FDA’s Expanded Access framework is what is being discussed or sought.

To reduce confusion for patients navigating access to pre-approval drugs, a team of experts has advocated for the adoption of an internationally accepted term for this process. In an article published in 2017 the experts, from NYU Langone’s Working Group on Compassionate Use and Preapproval Access (CUPA), concluded: “There is a pressing need to revisit and better align pre-approval access terminology at an international level.” They recommended globally adopting the term “pre-approval access” as an umbrella term for access to drugs that have not yet been approved by regulatory authorities in an individual country. Opponents of “pre-approval access” argue the term implies that the drug in question is definitely going to be approved.

The prevailing trend and path to consensus

From Early Access Programs to Compassionate Use and Right to Try, there is a wide array of terms used to describe the ways that patients can access pre-approval drugs. It is fair to assume that the plethora of terms creates unnecessary confusion for both patients and physicians seeking to make treatment decisions, not to mention the pharmaceutical industry.

At this point, Expanded Access, seems to be the umbrella term preferred by the pharmaceutical industry, especially if the main focus is the United States. To navigate this maze of terminology, every stakeholder needs to understand the complex global regulatory landscape and historical context to use the terms correctly. The aim here is to reduce confusion and friction and ultimately treat as many patients as possible for whom Clinical Trials and approved options have been exhausted.