Set up an Expanded Access Program in a few weeks (I)
This is Part 1 of a 3-part blog post about how pharmaceutical companies can prepare to offer Expanded Access. Expanded Access, which is also known as Early Access, Managed Access, Pre-Approval Access or Compassionate Use among other names, is a blanket term for a collection of international regulatory frameworks allowing physicians to request experimental medicines for patients with a serious or life-threatening condition, outside of ongoing clinical trials. Here in Part 1, we will discuss matters of a more philosophical nature, such as motivations for offering Expanded Access, and ethical considerations. In Part 2, we walk through a checklist of six core things that are needed operationally. Finally, Part 3 discusses the idea of collecting Real-World Data from patients being treated under Expanded Access.
We use the word "program" broadly, whereas in practice this term may have various distinct meanings. To some, the concept of an "Expanded Access program" implies a complex endeavor designed to support large volumes of cases, with detailed SOPs prescribing how to handle requests from many different countries, and perhaps even a multi-patient structure with predefined inclusion/exclusion criteria. You can add CROs and consulting firms into this mix. To other people, an "Expanded Access program" just means posting an Expanded Access policy online along with an email address for healthcare providers to reach out, expecting perhaps only a few requests per year.
Some pharmaceutical companies operate distinct "programs" for separate therapies in their pipeline. And the FDA even refers to the whole concept of Expanded Access as a "program".
If you're looking to offer Expanded Access to potentially thousands of patients annually, and you plan to hire a whole team and/or external advisors to do this, or if you don't already have a logistics solution in place, then you should probably spend more than just a few weeks preparing. Likewise, if you aspire to run your Expanded Access program using a software application that connects seamlessly to several existing computer systems, this will take time to arrange. (And we will revisit this topic in a subsequent post.)
But if your needs are humbler, this blog post may be for you. Maybe you're a smaller biotechnology company with therapeutics coming into phase 2 and 3 of clinical development, and you have data regarding safety and dosing. Perhaps you've already had healthcare providers, patients or patient-advocacy groups reaching out to you about these investigational products. Or maybe you've completed a pivotal trial and you need a pathway to continue supplying product to the trial patients until they can access it commercially. I plan to offer some helpful guidelines, both strategic and operational in nature, for offering Expanded Access to these patients.
The Philosophy of Expanded Access
First and foremost, Expanded Access is about offering compassion to a patient in need who has exhausted all other treatment options. While pharmaceutical manufacturers are allowed to collect data about patient outcomes (which is increasingly common), Expanded Access is patient treatment and not a clinical research study. Nor is it commercial activity.
Some pharmaceutical companies may be concerned about a perceived lack of control over what data is generated from Expanded Access, and how this is later interpreted and how it may impact regulatory approval processes. The FDA acknowledges that Expanded Access patients are expected to have a more advanced state of disease compared to typical clinical trial participants, and it bears this in mind when assessing any adverse event data from Expanded Access. I will merely highlight a 2017 paper titled Impact of Expanded Access on FDA Regulatory Action and Product Labeling, in which doctors Jonathan Jarow and Richard Moscicki of the FDA summarize six prior years of regulatory actions by concluding "There was no instance in which Expanded Access led to a negative regulatory decision regarding a drug application, and there was only one instance that safety events under Expanded Access had a potentially negative effect on product labeling. Concern that Expanded Access will have a negative impact on drug development and review is not based on the evidence and is unwarranted."
To assuage any apprehension about things potentially scaling upwards out of control: at a high level, there is no requirement for any pharmaceutical manufacturer to offer Expanded Access, and moreover there are multiple valid reasons for declining individual cases when proceeding might jeopardize the conduct of ongoing clinical trials or their drug supply, or present undue costs, or even if a company simply isn't set up to navigate the complex health and customs regulations in novel countries.
“One of the ancillary benefits of a well-conceived Expanded Access program is that it can help strike a positive first impression with research-oriented physicians. ”
Throughout the process of requesting access to investigational treatments, it is essential to review and approve cases with a sense of fairness—without favoritism or discrimination—and maintain an audit trail demonstrating this. From time to time, patients and families may attempt to influence the decision-making process, possibly via social media campaigns. A pertinent example is detailed in the 2021 Harvard Business School case study Who lives & who dies: Expanded Access for experimental drugs at Chimerix. Perhaps one lesson for the MBA students is that pharmaceutical manufacturers could stand to benefit from communicating more clearly to patients the reasons why Expanded Access isn't always possible. It's important for patients to understand that pharmaceutical companies are simply not allowed to pick favorites, especially those patients who might otherwise try to circumvent the system. (As an aside: this impartiality is easier to demonstrate if one is never exposed to the identity of the patient.)
Ultimately, regulators increasingly care about transparency with patients. They want you to make it plain and clear for patients and their physicians to understand if you offer Expanded Access, and if so, how they can contact you and how quickly you try to respond. The FDA in particular has recently issued guidance on this topic. They have also established the Reagan-Udall Foundation, whose mission is in part focused on helping patients and healthcare providers to better understand their options.
It bears reflecting on the fact that the vast majority of patients still do not or cannot access clinical trials, and for individuals with a serious or life-threatening medical condition who have exhausted the standard of care, Expanded Access is often the sole remaining avenue of hope for an effective treatment. If the patient is suitable, and there's an excess supply of an investigational therapy, and all other stars are aligned, the moral impetus for providing Expanded Access can be compelling.
Continue to Part 2 (A Checklist to Get Up and Running), or skip ahead to Part 3 (Real-World Data).