Navigating data collection under Early Access Programs

For patients with serious or life-threatening conditions, time is critical. Yet, accessing potentially beneficial treatments is often fraught with challenges when no approved standard therapies exist. Early access programs (EAPs) offer an important option, under regulated pathways, providing a potential mechanism for appropriate patients to receive investigational medicines ahead of formal approval. As innovation accelerates, these programs have become an essential bridge outside of clinical trials and routine care, offering hope where options are limited.

In this article, Rakesh Davda (EVP, Real World Evidence Solutions, Bionical Emas) and Pablo Duro-Ocana (Senior Medical Writer, Bionical Emas) share reflections on the evolving role of EAPs, the challenges of balancing treatment provision with data collection, and the opportunities for generating real-world evidence (RWE) to support access decisions and share early treatment insights with the scientific community.

Enabling access to investigational treatments outside of a clinical trial setting

By challenging the current standard of care and informing future decision-making, clinical trials are critical in delivering potentially promising investigational medical products to patients in need. For individuals with serious or life-threatening conditions, the importance of access to such treatments is paramount. However, vital design features of clinical research, including eligibility criteria, locality of sites and enrolment caps place, may inadvertently impact access to these patients who face urgent unmet needs.

In these cases, EAPs may offer a vital alternative. These programs refer to a range of regulations developed at national regulatory levels and are often described using varying terminology including, ‘Managed Access,’ ‘Compassionate Use’ and ‘Expanded Access.’ Where the anticipated benefit of treatment justifies the potential risk, EAPs may enable provision of investigational or pre-approved treatments outside of clinical trials. Access through EAPs is only appropriate where the disease or condition is serious or life-threatening and when there is no comparable or satisfactory alternative therapy option available.

"For patients living with serious or life-threatening conditions, waiting for full regulatory approval simply isn’t an option. EAPs may offer a crucial pathway for access when time matters most."

While investigational products should ideally be accessed through clinical trials, EAPs are designed to ensure that provision outside of trials does not compromise ongoing clinical development or regulatory processes. Most requests for access relate to rare diseases, hematology or oncology, where EAPs provide access for patients with substantial unmet need.

Building data collection into access programs

While the primary purpose of EAPs is to provide access to new treatments, with appropriate regulatory centric and compliant design, data collection can yield valuable pre-approval and pre-reimbursement insights. Interest has been heightened by the broader evolving commitment towards leveraging real-world data (RWD) to enhance access to innovative treatments, as exemplified by advances in guidance provided by institutions such as the National Institute for Health and Care Excellence (NICE) and the US FDA.

“In parallel to regulator and payer interest, there has been a notable increase in EAP treatment experience presented through conference abstracts and publications.”

Despite the growing coverage, practical guidance on how to operationalize EAP data collection remains limited where regulations allow it. With treatment provision as the priority, data collection can be overlooked and the opportunity missed. When data are published, they often take the form of retrospective chart reviews, typically initiated after marketing authorization or reimbursement. The fragmented approach between countries, perceived complexity, physician/patient burden and population heterogeneity can further complicate efforts to collect meaningful data.

Identifying a low-burden and balanced approach

Fundamental in determining the safety and effectiveness, research infrastructures are primarily geared towards delivering prospective clinical trials. In contrast, EAPs often involve individual, unscheduled treatment requests across multiple sites, which creates significant challenges when seeking to establish a structured, multinational, compliant, and low-burden approach to data collection. Nevertheless, with early country-level feasibility assessment, including careful consideration of principles relating to data privacy and security, the secondary use of aggregated health data from submitted EAP treatment requests provides basic data collection with minimal burden. The approach can yield insights on medical eligibility and therapy initiation, then, over time, resupply and discontinuation records provide valuable information on ongoing treatment experience. Incorporating minimal efficacy data, where feasible, is an evolving area that can complement clinical development and enhance understanding of therapeutic use. However, this potential to complement trial findings must be balanced against inherent limitations.

The lack of guidance creates uncertainty on the appropriate operational approach for collection and compliant use. Even with a minimalist mindset, attempts to collect data beyond what is needed to initiate and monitor treatment can strain resources and risk undermining the, “no strings attached," and ”non-research orientation of EAPs. With the intention to minimize EAP delivery burden and potential scarcity of site-level resource, realistic expectations should be placed on data quality. Systematic examination of data consistency and completeness, utilizing mechanisms such as validation and edit checks, are generally not feasible in this context. Additionally, efforts to address known priority data gaps, such as capturing prior therapy information at the country level, would likely pose challenges.

Developing a regulatory-led data collection approach while prioritizing access

Despite growing interest in capturing insights from EAP treatment experience, operational guidance to support such endeavors remains sparse. Although possibilities exist to align broader data collection strategies at a multinational level, approval and operational aspects require adaptation at the country-level. This is primarily shaped by the regulatory route selected to prioritize access, where treatment supply could be on an individual or group/cohort basis, depending on factors such as the anticipated number of treatment requests, the stage of clinical development, and global licensing status. Illustrating this complexity, the table below provides a regulatory overview of the multiple EAP routes in some key markets. 

A more comprehensive methodology for data collection may be instigated by the physician, regulator or sponsor, offering an opportunity for collaboration. Considering the licensing status and unsolicited nature of requests, where sponsors are involved, collection must be carried out in a compliant manner, in accordance with applicable codes, laws and regulations. Navigating a broader prospective approach requires feasibility work with key stakeholders and planning early during the EAP planning phase.

Successfully adapting existing machinery for broader data collection

Under defined routes, France and the UK have established frameworks to guide applicants on incorporating data collection, though regulatory expectations differ.

In France, Early Access (pre-marketing) Authorization (AAP/AP1) clearly stipulates data collection requirements in a protocol (PUT-RD). In addition to parameters relating to clinical characteristics, efficacy and safety, there is a general requirement to capture patient reported outcome measures (PROMs). The manufacturer is expected to play an active role in data collection and monitoring, with the proportion of missing data limited. Importantly, data collected during the program can be used to support the reimbursement dossier.

By contrast, requirements are generally reduced for Early Access (post-marketing authorization) Authorization (AAP/AP2), with patients again treated and monitored based on criteria pre-defined within a PUT-RD. Similarly, individual patient access routes reduce the emphasis on data collection. For example, following an initial Compassionate Use Authorisation (AAC), a less comprehensive protocol (PUT-SP) outlines data requirements. 

In the UK, the Early Access to Medicines Scheme (EAMS) includes a supporting framework for the systematic collection of data. The planning phase includes the opportunity for early engagement between the sponsor and the National Institute for Health and Care Excellence (NICE), taking future health technology assessment (HTA) needs into consideration. The data collection methodology is agreed collaboratively and may range from using an existing registry to implementing bespoke electronic case report forms, depending on stakeholder consensus.

An additional benefit of EAMS is a faster NHS adoption following a positive reimbursement recommendation. However, broader data collection is not mandated and is generally lighter in terms of the systematic examination of data completeness in comparison to France. When access is provided outside of EAMS via individual patient arrangements, the UK’s NHS research infrastructure can still effectively support longitudinal data initiatives, including the collection of PROMs.

In the US, cohort-based expanded access pathways require the submission of a protocol, which is reviewed by both the FDA and a competent Institutional Review Board (IRB). Although primarily focused on supporting any treatment decision, data collection plans can be outlined in the submission. While sponsors should avoid mandating the collection of additional data parameters, early dialogue with key stakeholders in the design phase is recommended to maximize engagement.

Elsewhere, similar opportunities to outline plans in the submitted regulatory dossier exist in Italy and Germany. Even if no formal objections are raised by the competent authority, local guidance must still be followed to ensure appropriate classification of the proposed data collection and compliant conduct once approved. Ethical considerations should also be addressed, with feedback incorporated before data collection begins. In Spain, the collection of compassionate use data requires working under observational study regulations. This requires a more formal process, involving reference to ethics opinion, followed by site-level negotiation and regulatory submissions before data collection approval.

Designing real-world data collection without compromising access prioritization

When designing the RWD collection plan with EAPs, it is important to keep expectations realistic and remember the aim of the program: to provide patients with access to investigational medicines. Therefore, collecting data that requires additional patient monitoring or medical procedures beyond the standard of care will not be feasible and is more suited to the clinical development pathway.

“Selecting minimal outcomes aligned to the broader evidence strategy will reduce the burden on both patients and healthcare providers. Ultimately, accompanying data collection must not be seen as an obstacle to treatment provision or the recruitment of patients to clinical trials.”

For illustrative purposes, this article presents an overview of opportunities across some key markets: US, Germany, France, Italy, Spain and UK. As interest in leveraging RWD from EAPs gathers momentum, operational guidance and collection infrastructure to support longitudinal data initiatives must continue to evolve. Our experience suggests that key stakeholders are open to dialogue on EAP data collection.

“With its unique pre-approval and pre-reimbursement positioning, approached compliantly EAPs can offer valuable early insights in supporting the broader value proposition of new therapies.”

Authors

Rakesh Davda, MSc
EVP Real World Evidence Solutions, Bionical Emas

Rakesh Davda has broad industry experience across commercial, medical affairs, and market access, with expertise in international health technology assessment in multiple jurisdictions. He has extensive experience with global EAPs from an industry and service provider perspective, and leads teams liaising with sponsors, regulators, clinicians, and patient groups to design and implement real-world data initiatives.

Pablo Duro-Ocana, PhD
Senior Medical Writer, Bionical Emas

Dr Pablo Duro-Ocana is a Senior Medical Writer at Bionical Emas specializing in drafting regulatory documents and medical communications for EAP and real-world data initiatives. With a background in muscle physiology and surgical recovery, he has authored several scientific publications in the field, bringing strong research-based expertise to medical writing.

Disclaimer

The opinions expressed in this feature are those of the authors and do not necessarily reflect the views of The Evidence Base® or Becaris Publishing Ltd.

Sponsorship for this Guest Column was provided by Bionical Emas.