The 2nd Operationalise Early Access Programmes Summit Europe provided practical solutions to the industry’s most pressing issues, including drug supply, regulatory harmonization, and real-world evidence collection, while also exploring emerging challenges such as reimbursement, integration of pre- and post-trial access programs and scoping. 

Stuart Bell, Senior Vice President, Early Access at Inceptua ran a workshop at the conference called “Effectively Collect Real World Evidence for Early Access Programs”. Following the workshop, we have asked Stuart a few questions to reflect on the experience and key take-aways from the session. 

1. What are the latest trends in relation to data collection and EAPs? 

Collecting data in an Early Access Program (EAP) has become increasingly common, due to a greater understanding of its potential value, and in part due to the fact that EAPs are becoming more of a standard component of the development and launch for medicines.

EAP Real-World-Evidence (RWE) or data can be, and is, used as supplemental data for Health Technology Assessment (HTA) and Pricing and Reimbursement (P&R) submissions, but it is still unclear how such data is viewed by authorities responsible for conducting these HTAs. 

Generally, HTA bodies are skeptical of RWE to some degree. Utilization of RWE varies considerably between countries, and even the most ‘robust’ RWE studies are often retrospective, and in some cases have actually resulted in a restriction to the label and a price decrease* 

Most published papers on RWE from EAPs are based on retrospective analyses, more akin to a clinical trial, rather than real-time data capture alongside an ongoing EAP. 

It’s apparent though that the trend is towards more data collection in EAPs, although up to now the practical usage of such data is still relatively low. 

*12/25 HTA assessments (across Canada, France, Sweden and the UK) involving RWE resulted in a restricted label and / or price decrease. Source: Impact of RWE on HTA Decision-making. IQVIA, 2022. 

2. During the workshop, you seemed quite skeptical regarding the utility of data collected in Early Access Programs. Why is that? 

My intention was not to be pessimistic. There are reasons to be optimistic in this context as well. I only want to level-set expectations.  

For example, outputs from the Heads of Medicines Agencies Survey results* showed that: 

• No HTA/regulator responder said RWE was essential to fill knowledge gaps in Clinical Trial data 
• HTA/regulators did agree that RWE was important for ‘selected regulatory purposes’, most notably Pharmacovigilance 

Why did the responders have this skepticism? 

• There is a mismatch between robust RWE, and what is required for regulatory decisions 
• The quality and transparency of the data sources vary greatly 
• The role of the stakeholders and conflicts of interest is a concern 

*Adapted from: Heads of Medicines Agencies Survey results: Use(-fulness) of RWE in regulatory decisions. Multi-stakeholder workshop on Real World Data (RWD) quality and experience in use of Real-World Evidence (RWE) for regulatory decision-making. 26-27 June 2023.

With that in mind, there is a lot of good data available as standard through an EAP, primarily to provide insight and identify signals which may inform further studies or retrospective analyses, rather than being used directly for Regulatory and/or HTA Submissions.  

4. RWE in EAPs – what is possible in practice? 

If we had free reign to design RWE studies as we would like, what would that look like? Real time, verified data? How do we get to that?  

The ideal scenario would be robust, contemporaneous data collection alongside an EAP. A ‘neater’ approach is to carefully select a few data points for collection (as part of the order process) during the EAP, designed to identify a specific signal. Where these data suggest further exploration, then there are many options open to the program sponsor e.g. conduct a retrospective chart review with all the rigor required to collect regulatory-grade data, or run a further clinical trial specifically looking at those endpoints. 

Basically, use your EAP discriminately to lessen the burden on physicians and be more cost-effective through only conducting detailed data collection where you have a reasonable expectation that the time and costs are worthwhile. Given the current low utilization of EAP data, including extensive data collection in EAPs should be carefully considered, as it can present an additional barrier to participating physicians. 

5. What are your final thoughts and recommendations? 

• Working with many different companies, there is a wide range of attitudes and tolerances to data collection in EAPs 
• Nearly all clients express an interest in data collection 
• Many view it as the ‘golden bullet’ 
• It is important to think about the purpose of collecting data, as it is only used to support Regulatory or HTA discussions in a limited number of cases, and when it is used sometimes it can have a derogative, rather than positive effect  
• Carefully select a few data points for collection during the EAP, designed to identify a specific signal. Where these data suggest further exploration, it is then warranted to go back and commission a more detailed data collection with all the rigor required to collect regulatory-grade data. 
• Some clients do collect significant amounts of data through the order (and between orders) process with no pushback from physicians. We find this is often the most practical approach. 
• Issues arise around long-term follow-up (particularly for a one-off/gene therapy or acute treatments), emergency treatments (asking physicians to provide a lot of data for a patient who could literally die that day), and absence of source data verification (how do we know the physician entered real data?) 
• Finding a balance between ‘like to have’ and ‘reasonable to have’ is key