Set up an Expanded Access Program in a few weeks (III)
This is Part 3 of a 3-part blog post about how pharmaceutical companies can prepare to offer Expanded Access, in which we will review the option of collecting Real-World Data from patients being treated under this regulatory pathway. In case you missed them, see Part 1 (The Philosophy of Expanded Access) and Part 2 (A Checklist to Get Up and Running).
Real-World Data
The collection of Real-World Data from Expanded Access treatment is not yet a widespread practice, but it's growing. Regulators are helping to drive this adoption: quoting the 2020 paper Making it count: Extracting Real World Data from Compassionate Use and Expanded Access Programs, "As per the 2016 21st Century Cures Act, the FDA is obligated to seek alternatives to the expensive, narrow and rigid RCT paradigm and among other efforts, incorporate Real-World Evidence into its approval process."
And Real-World Data is an increasingly pertinent element of clinical development planning: in a 2019 paper titled Expanded Access as a source of Real-World Data: An overview of FDA and EMA approvals, the authors tabulate four dozen examples of regulatory approvals at least partly supported by efficacy data from Expanded Access, and four examples of treatments for rare conditions that were approved solely based on Expanded Access.
Beyond this, Real-World Data has also become more relevant in understanding potential new indications. An example is the CheckMate 218 Expanded Access study of nivolumab in combination with ipilimumab (a.k.a. Opdivo and Yervoy, two of the first checkpoint inhibitor immuno-oncology drugs) in patients with advanced melanoma. The sponsor, Bristol Myers Squibb, and study investigators reported in 2020 that "nivolumab plus ipilimumab demonstrated high survival rates and safety outcomes consistent with those from randomized clinical trials, further supporting the use of this combination for advanced melanoma across multiple subgroups".
Partly owing to the effectiveness of checkpoint inhibitors against such a variety of cancers, Real-World Data has been instrumental to the development of these promising new therapies. Additionally, healthcare payors may lean on Real-World Data to support reimbursement decisions.
I will offer three guidelines for embracing Real-World Data in a practical way:
First, keep things as simple as possible. Don't collect Real-World Data just for the sake of it, especially without a plan for how the data will be analyzed—including for any safety signals.
Second, have a plan for collecting the data in a streamlined and efficient way, with minimal extra work for the patient's healthcare provider team. Over time, we'll see technologies brought to bear on this challenge such as connectivity with Electronic Medical Records, machine learning tools to interpret and structure clinical notes, and mobile apps to collect patient-reported outcomes. A good starting point is to offer the patient's clinical team an easy online interface for them to enter the necessary data, as specified by you. It needs to have healthcare-grade security. And consider collecting Real-World Data when resupply is being requested (if applicable), so that healthcare providers can complete both tasks at the same time.
Third, if you want to collect Real-World Data and possibly present it to regulators, you should consider whether you'll do this using an electronic system, and whether you need to validate the compliance of that system with Good Clinical Practice guidelines and regulations such as HIPAA and 21 CFR Part 11 in the U.S. and Annex 11 in the E.U. This exercise is beyond the scope of this blog post, and may present another example of when planning for an Expanded Access program can take longer than just a few weeks.
Our Final Thoughts
Expanded Access is an important pathway for seriously ill patients to receive potentially life-changing investigational medical treatments. And it's growing, buoyed by strong support from regulatory authorities internationally, not to mention other factors which we will examine in a subsequent post.
Among therapeutic areas, Expanded Access is particularly relevant for rare diseases and difficult-to-treat cancers, which happen to represent two patient demographics imperfectly suited to traditional clinical trials. In the case of rare diseases, patients tend to be few and far between, making the travel logistics of clinical trials more challenging and expensive. And cancer patients who have exhausted the Standard of Care can be so weakened by surgery, chemotherapy and radiation as to no longer meet the strict inclusion/exclusion criteria of a typical clinical trial. For this and other reasons, it's a wonderful development that more pharmaceutical manufacturers are offering Expanded Access, and making the process easier for healthcare providers.
In summary, Expanded Access is always motivated by compassion for patients with a serious medical condition who have used up all other options (hence the commonly-used alternative name Compassionate Use). With this crucial ethical foundation in place, the biopharma sponsors who offer Expanded Access may experience auxiliary benefits, including an improved dialogue with research-oriented physicians, insights about new therapeutic applications for existing products and the design of future clinical trials, and increasingly, Real-World Evidence potentially supporting regulatory approvals and/or reimbursement decisions by payors.
MedaSystems' role in global Expanded Access is to offer pharmaceutical manufacturers and their outside advisors a software platform built specifically for managing Expanded Access programs in a compliant and scalable way. For more details, please get in touch!