The role of pharmacists in increasing patient access to ‘compassionate use’ programmes

During the COVID-19 pandemic, as healthcare systems sought ways to better prevent, treat and manage a previously unseen infection, rapid access to promising novel investigational therapies based on emerging scientific evidence from clinical trials was crucial. This ‘early’ access pathway was via ‘compassionate use’ (CU) programmes, which are something I’ve been passionate about for many years.

Programmes of this kind are not new, with documented use in Europe since the 1990s for the early provision of investigational anti-retrovirals during the HIV/AIDS crisis. CU enables the provision of a medicine (generally free of charge) prior to market authorisation, at the request of a treating physician, for a patient suffering from a serious or life-threatening condition when all available treatment options have been exhausted and enrolment in a clinical trial is not possible.

CU also addresses the time lag between confirmatory trial completion, regulatory approval and subsequent availability of a medicine in a healthcare system, which may be anywhere between 120 and 1,000 days, depending on the country.

The UK has clear regulations for CU in place. The Medicines and Healthcare products Regulatory Agency (MHRA) provides guidance for the supply of unlicensed medicinal products in and from the UK. In 2014, the MHRA also established the Early Access to Medicines Scheme (EAMS), a framework for the early use of an unlicensed medicine when there is a clear unmet medical need, and allows for collection of data and their use for an earlier appraisal for routine use by the National Institute for Health and Care Excellence.

Disparity in ‘compassionate use’ access between countries

On average, Novartis processes around 10,000 CU requests per year. These are assessed by its medical experts promptly once we have all the necessary information and 95% are approved, giving us a huge pool of data to tap into and explore the factors that drive and impact CU requests at a country level. Our findings, published in JAMA in April 2022, show significant global disparities in CU requests.

For example, by analysing 31,711 requests received over a 36-month period, we found that:

• The vast majority (87%) came from high-income countries, with 73% from only ten of these countries;
• An even larger proportion (94%) came from countries with CU regulations made publicly available online;
• Almost all (96%) came from countries with a high level of clinical trial activity.

Unsurprisingly, our analysis showed that, in absolute numbers, the UK is among the top ten high-income countries to make CU requests; however, it lags behind similar countries, including most in Europe, in terms of CU requests per million population. Inevitably, there is also strong regional variability, with a high proportion of requests received from teaching hospitals/academic centres.

Addressing these disparities and improving the access to CU medicines overall requires multi-stakeholder efforts from regulators, healthcare professionals and the pharmaceutical industry. Having originally trained as a pharmacist, I have written this article with a focus on the role this profession can play in and beyond the UK.

The role of pharmacists in ‘compassionate use’ programmes

There is a huge opportunity to increase the awareness of CU regulations and processes among UK healthcare providers. As medicines experts, pharmacists are an important information resource in treating physicians, patients and caregivers. In recent years, the barriers to gathering information have decreased, with a variety of reliable and openly accessible sources on investigational medicines and CU programmes becoming available.

Since 2016, the United States Department of Health and Human Service’s ‘Final Rule‘ has required companies to disclose available CU programmes publicly via the US National Library of Medicine’s ClinicalTrials.gov. The Reagan Udall Foundation for the US Food and Drug Administration’s NAVIGATOR tool is another useful resource that lists available CU compounds and how they can be accessed. Congresses and publication highlights — for example in oncology, neurology and rare diseases — are useful information sources on promising investigational therapies.

Pharmacists obtain and manage CU medicines at a healthcare institution level and have a pivotal role in facilitating the overall prescriber and patient experience. By working with regulatory agencies alongside other stakeholders, pharmacists can help ensure that local CU regulations continually evolve to address urgent patient needs and ultimately enable prompt, non-bureaucratic access to potentially life-saving medicines. In France, for example, information on CU, available programmes and the physician application process can be accessed via a single online portal developed by the regulators. 

A win-win outcome for all

As well as benefiting patients and healthcare providers, CU is an invaluable opportunity to collect real-world data, which can support product approval and get essential medicines into the clinic faster. The importance of this was demonstrated in April 2022 through an FDA approval of alpelisib (Vijoice; Novartis Pharmaceuticals) for PIK3CA-related overgrowth spectrum based solely on real-world data obtained from patients who were part of a CU programme. 

The COVID-19 pandemic spotlighted the value of CU, and our research is beginning to uncover some of the drivers of increased CU programme use. We now need to work together to raise awareness and understand this area more deeply — more research, more conversations, more experience sharing.

Our hope is that our research will be a catalyst for these discussions and help translate the learnings into improved early access to novel lifesaving products for patients with unmet medical needs.

Paul Aliu is head of the global governance office in the cross-divisional chief medical office at Novartis