Expanded Access Programs: Ethical and Practical Considerations for Biopharmaceutical Sponsors

Abstract

Expanded access is a regulatory mechanism by which an investigational drug can be made available outside of a clinical trial to treat patients with serious or life-threatening conditions for which there are no satisfactory treatment options. An expanded access program (EAP) is the formal plan under which preapproval access to an investigational drug can be provided to a group of patients. Although an EAP is a regulated program, the decision to authorize an EAP is the responsibility of the biopharmaceutical sponsor. Because of the significant impact an EAP can have on current patients, drug development, and future patients, we propose that a sponsor’s decision must be based not only on regulatory criteria but also on ethical and practical considerations regarding implementation of an EAP. Such an approach will help ensure that decisions and plans uphold ethical precepts such as fairness, promoting good, and minimizing risk of harm.

Advanced Medical Care Program for the Rapid Introduction of Healthcare Technologies to the National Health Insurance System in Japan

“…Such attempts to compensating drag lags with a framework of Expanded access/Compassionate Use (EAP/CU) is being implemented in many countries. 10,11 EAP/ CU is exceptionally applied for a patient in a life-threatening condition where investigational drugs are usually on the market but difficult to obtain the regulatory authorization. However, there is a controversy over the use of EAP/CU data for market approvals.…”

The Moral Case for Granting Catastrophically Ill Patients the Right to Access Unregistered Medical Interventions

“…40 Representatives of a major pharmaceutical company also warned that "any access program that diverts resources away from a sponsor's primary role and impedes drug development in the short term may threaten the health of future patients by delaying regulatory approval and market access." 41 While permissive access regimes might not render valid clinical trials impossible, as Annas claims, they would likely delay drug R&D. More recently a variety of these kind of argument has been brought up again by London and colleagues who argue that respecting individual patient choice would be detrimental to the integrity of the research enterprise. 42 What can be replied to concerns about R&D delays, given their harmful impact on future generations of patients?…”

“…A number of authors have expressed a different concern about at least one foreseeable outcome of a permissive access regime, delays in trial recruitment and as a consequence of this, delays in drug R&D. 39 Future generations of patients would arguably be harmed by the refusal of current patients to participate in clinical research. George Annas, for instance, wrote, “[M]aking unproven drugs available is poor policy, [because] if unproven remedies are easily available, it will be impossible to do scientifically valid trials of new drugs.” 40 Representatives of a major pharmaceutical company also warned that “any access program that diverts resources away from a sponsor's primary role and impedes drug development in the short term may threaten the health of future patients by delaying regulatory approval and market access.” 41 While permissive access regimes might not render valid clinical trials impossible, as Annas claims, they would likely delay drug R&D. More recently a variety of these kind of argument has been brought up again by London and colleagues who argue that respecting individual patient choice would be detrimental to the integrity of the research enterprise. 42 What can be replied to concerns about R&D delays, given their harmful impact on future generations of patients?…”

Implementing a Global Expanded Access Program (EAP) for Infantile-Onset Spinal Muscular Atrophy (Type I): Understanding the Imperative, Impact and Challenges

“…An EAP is a non-promoted, optional program that provides eligible patients with access to an investigational treatment, before regulatory approval and commercial availability [14, 15]. EAPs, also known as Compassionate Use or Named Patient programs, are most commonly offered for rare diseases for which treatment options are unavailable or not tolerated, and typically for severe or life-threatening diseases [15].…”