Harnessing Real-World Evidence for Health Technology Assessment Amid Evolving Regulations and Payer Needs

In the rapidly evolving healthcare landscape, Real-World Evidence (RWE) has transcended being just a buzzword and is now a critical component in evaluating the value of new health technologies. As healthcare decision-makers increasingly prioritize evidence that mirrors real clinical practice, RWE is revolutionizing the way regulators, payers, and Health Technology Assessment (HTA) bodies assess medical innovations.

At HEOR Horizons, we understand that effectively navigating this shift requires a comprehensive grasp of how RWE is influencing the future of access and reimbursement. This blog explores the evolving significance of RWE in HTA and outlines how life sciences companies can strategically utilize it to meet current regulatory and payer demands.

What Is RWE and Why Is It Crucial?

Real-World Evidence is derived from Real-World Data (RWD)—information collected outside traditional clinical trials, such as electronic health records, claims data, patient registries, mobile apps, and wearable devices.

While randomized controlled trials (RCTs) remain the gold standard for efficacy assessment, they often fail to reflect treatment performance in everyday clinical settings. RWE bridges this gap. According to the U.S. FDA, RWE is “the clinical evidence regarding the usage and potential benefits or risks of a medical product derived from analysis of RWD” (FDA, 2018).

For regulators, payers, and HTA bodies, RWE provides a more comprehensive view of a therapy’s value, especially in diverse, real-world patient populations.

A New Era for HTA: RWE Takes Center Stage

Health Technology Assessment bodies are responsible for evaluating the clinical and cost-effectiveness of therapies to guide funding decisions. Traditionally, they relied heavily on RCTs. However, with increasing pressure to approve therapies quickly, particularly in areas like oncology, rare diseases, and cell and gene therapies, RWE has become an essential supplement.

A study by Makady et al. (2017) discovered that most European HTA agencies already incorporate RWE into their assessments, especially when:

• RCT evidence is limited or short-term,

• Long-term outcomes are required,

• Or real-world effectiveness varies by population.

Agencies such as NICE (UK) and ZIN (Netherlands) now actively engage with manufacturers to discuss how RWE can aid decision-making, particularly under managed access schemes or early access pathways.

Regulators Are Moving Quickly

Regulatory agencies are also rapidly adopting RWE.

• In the United States, the FDA’s Real-World Evidence Framework (2021) outlines how RWE can support approvals for new drug indications and post-market safety monitoring. The agency emphasizes data quality, relevance, and transparent methodologies.

• In Europe, the EMA’s DARWIN EU (Data Analysis and Real World Interrogation Network) initiative is developing a coordinated real-world data ecosystem. It aims to help regulators and HTA bodies access and analyze high-quality RWD across Europe (EMA, 2022).

These initiatives indicate that RWE is becoming a regulatory expectation rather than a mere option.

Payers Demand More Than Trial Data

Payers face pressure to manage costs while providing value-based care. For them, RWE offers insights into treatment performance in real-world settings, addressing questions such as:

• Does the treatment reduce hospitalizations?

• What is the real-world adherence like?

• Is it cost-effective in diverse patient populations?

The German G-BA, for example, routinely requests post-marketing observational data to reassess products under conditional reimbursement. Similarly, value-based contracts in the U.S. often depend on RWE to track outcomes and adjust pricing (ISPOR, 2020).

The key takeaway? RWE is central to demonstrating a product’s value beyond regulatory approval and increasingly vital for successful market access.

Challenges Remain

Despite its potential, using RWE effectively requires caution and precision:

• Data quality is a significant concern. Inconsistent coding, missing values, or poor interoperability can undermine trust.

• Methodology matters. Without the control of RCTs, observational studies must employ techniques like propensity score matching to minimize bias (Berger et al., 2019).

• Global variability in how HTA bodies assess RWE can complicate cross-country submissions.

Initiatives like the IMI GetReal project are fostering consensus on standards, tools, and best practices for integrating RWE into HTA frameworks (IMI, 2016).

How Can Companies Prepare?

At HEOR Horizons, we guide our clients through the complexities of effectively using RWE—because successful implementation begins early.

Here are some key strategies:

• Engage HTA bodies and payers early: Seek scientific advice on the type of RWE they’ll accept.

• Invest in data infrastructure: Ensure RWD sources are clean, representative, and regulatory-ready.

• Be transparent and methodologically sound: Use established reporting standards like RECORD or STaRT-RWE.

• Think long-term: Consider how RWE can support lifecycle evidence, from early access to post-launch value demonstration.

Case Studies: Real-World Applications

• CAR-T Therapies: Due to limited trial data, NICE relied on real-world registry and compassionate use data to evaluate CAR-T therapies for cancer patients (NICE, 2021).

• Diabetes Management in Sweden: The Swedish TLV used national registry data to assess the long-term effectiveness and safety of SGLT2 inhibitors in type 2 diabetes (TLV, 2020).

These examples illustrate how RWE is already supporting critical decisions in areas where speed and long-term insight are essential.

Conclusion: The Time for RWE Is Now

Real-world evidence is fundamentally transforming how we evaluate new therapies. As regulators, HTA bodies, and payers continue to adapt their expectations, companies must be prepared to deliver high-quality, decision-grade RWE.

At HEOR Horizons, we are dedicated to helping life sciences companies fully leverage RWE—from strategy to execution. Whether you’re developing an early access value story, preparing for HTA submissions, or negotiating with payers, we’re here to help you confidently navigate this evolving landscape.