Compassionate Use/Expanded Access programs: Three steps to improve their implementation for the benefit of all
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Compassionate Use or Expanded Access is a treatment option for patients in desperate need which can be independently requested by a treating physician, providing access to locally unlicensed medications when all approved treatment options have been exhausted and enrollment in a clinical trial is not possible. There is no doubt about the human value of these programs for patients with no other option, and it’s also increasingly clear just how beneficial they can be for the entire health care ecosystem in addressing the unmet medical needs of patients. But many stakeholders, from governments, healthcare institutions to pharma companies, are not set up to make the best use of compassionate use. The time to change that is now.
I have been passionate about compassionate use programs for many years, but two recent events have crystallized their importance for me — indicating that we have reached a pivotal moment where the full potential of these programs is there for all to see, if the collective will is there to grasp it.
First, in April, the FDA approved a therapy for a rare disease based solely on real-world data obtained from patients who were part of a compassionate use program. This was unprecedented and shows just how crucial data collection in compassionate use has become to accelerate approval of much-needed therapies, especially in rare diseases where there are often none or very few treatment options.
Second, my colleagues and I investigated factors associated with compassionate use requests received at Novartis over a three-year period. The data published in the Journal of American Medical Association (JAMA) Health Forum showed that of the 31,711 compassionate use requests from 110countries, 87% were from high-income countries. An even larger proportion – 94% – came from countries with compassionate use regulations made publicly available on the internet, and almost all (96%) came from countries with a high level of clinical trial activity. While these data clearly reveal vast disparities at the macroeconomic level, I believe they also shine a light on the path forward — for governments, regulators and pharma alike.
As a pharma executive, I am mostly focused on what companies can do to optimize their compassionate use programs. I’ve been involved in this space for well over a decade, and the evolution during this period has been phenomenal. At Novartis alone, we now receive on average about 10,000 requests every year, with an approval rate of around 95%. We have garnered significant experience and understanding over time, which we have used to push the boundaries, pave the path forward and improve our programs in the following ways:
Find the will before the way
First, there must be a genuine desire to implement and support compassionate use programs — and it must start at the top. Healthcare companies have a responsibility to enable access to their innovative medicines to the patients who need them most. At Novartis, we are committed to helping ensure that our medicines are accessible to as many patients as possible, irrespective of where they come from. We implement compassionate use programs because it’s the right thing to do.
Owing to the nature of the regulatory and reimbursement process, there is often a gap of several months to years between generation of robust efficacy and safety data in trials and local marketing authorization with subsequent local patient access. Compassionate use programs enable the provision of cutting-edge therapies to those who desperately need them during this window. For companies, these programs also provide opportunities for the collection of real-world data from a broader patient population beyond the clinical trial, and an opportunity to engage with patient communities, often invaluable in rare diseases.
I believe one of the main reasons for our high rate of compassionate use approvals is because there’s an underpinning philosophy where the default is to say ‘yes’, unless there’s a justified medical or scientific rationale not to. Having this patient-centric mindset in place and the willingness to deploy resources in this area is essential.
Instill a robust company policy enabled by an end-to-end request system
A commitment to compassionate use means having the policies, end-to-end processes, and systems in place to manage requests in a prompt, fair and efficient manner. The US 21st Century Cures Act has since 2017 required that pharma companies developing investigational drugs (including biologics) make their policies regarding evaluating and responding to requests readily and publicly available, e.g. on company websites.
A centralized policy and governance provide a solid foundation. We have a dedicated group in place acting as a Center of Excellence, which has holistic oversight and ensures all elements are in place. This also includes incorporating adequate guardrails into the process, the handling of exceptions, addressing initial pediatric use and dosing questions (e.g. managed with our integrated safety assessment board), and the use of an external independent bioethics advisory committee (IBAC) for selected ethical challenges related to compassionate use.
With the increasing use of genetic testing and evolution of targeted therapies, it is important to consider how individual patient requests will be handled, especially for indications where the company has no active or ongoing development program.
It’s also essential to build a user-friendly compassionate use request system — any difficulties accessing or using the system, or limitations to who can use it, are likely to deter treating physicians and hinder the receipt of requests.
We launched an online request system in December 2019 to streamline request management. It’s simple and can be used by physicians anywhere in the world. Treating physicians can submit and handle a request through any desktop or mobile device. In general, it enables a speedy turnaround time — most review outcomes are provided within five working days, ensuring the patient and treating physician do not lose a lot of time.
Partner with others and share your findings
We believe openness and partnerships are vital pieces of the puzzle. The data from our JAMA analysis was limited to the experience of a single company, and results may differ across other organizations. In light of this, we would welcome similar data analysis from our industry peers and regulators to help inform and enrich the overall knowledge base in this space.
There are ongoing best-practice collaborations between multiple stakeholders — including pharma companies, patient groups, regulators, governments, healthcare professionals, vendors and academia — to ensure that patient access needs in compassionate use are addressed holistically. It is important to be a part of these conversations and collaborations to ensure diverse perspectives and experiences are considered in the development of solutions to help address patient access needs globally.
There has been so much progress already, but there’s still a lot that could be done to improve the implementation of compassionate use programs around the world. The best way forward is together, for the ultimate benefit of patients.