(001) A comparison of regulatory frameworks for real-world data (RWD) collection within Early Access Programs (EAP) in the US, EU and Japan

Background: Historically, Early or Expanded Access programmes (EAPs) were only deemed fit for providing compassionate access to treatment and not for research. However, EAP are now generally considered to be a source of real-world data (RWD) as they can provide useful clinical information, and evidence derived can be leveraged to impact regulatory or payer decision making.

Objectives: To identify consistencies and discrepancies in the set of real-world design and outcomes data that can be collected in the context of an EAP to assess treatment benefit-risk across the United States (US), Europe and Japan.

Methods: We searched country-specific EAP regulatory guidelines for data collection themes for 7 countries: the US, France, Germany, Italy, Spain, the United Kingdom, and Japan. We manually extracted the following protocol design guidance for EAPs: data collection variables and outcomes, safety requirements, number of patients, duration of follow-up, and if there were any recommendations for analyses of the data collected and its reporting.

Results: Data collection guidelines for patients treated within an EAP tend to vary by country. Across most types of EAPs in the 7 countries, safety data collection is always required. None of the countries prohibit data collection beyond safety outcomes within their guidelines. France and the UK are the only two countries which explicitly mandate the collection of a restricted number of variables regarding patient characteristics, EAP treatment conditions of use and efficacy assessments. France also requires the collection of prescriber characteristics and patient reported outcome measures. In Italy and Spain, depending on the type of EAP or if requested in the specific EAP authorization, data on the disease and treatment course may need to be collected. In the US, Germany, and Japan, EAPs are more focused on safety. No guidance is provided with regards to the follow-up duration of data collection. Analyses performed are expected to be descriptive. Results of data collection should be provided per local regulatory requirements: at least once during the EAP (Japan), annually (US, Germany), every 3 months (Italy, UK), or at a frequency agreed on a case-by-case basis (France, Spain).

Conclusions: Additional guidance by regulatory bodies on how to enable and ensure consistency in data collection during an EAP is needed to improve the validity of this research for regulatory and payer submission, especially in Europe. More uniform guidance would allow scientifically robust, practical, and ethical data collection approaches.