With real-world evidence (RWE) growing in influence across health care, regulatory and health technology assessment (HTA) bodies continue to issue recommendations for biopharma to articulate standards around RWE generation and use.
However, as discussed during the session “RWE guidance and frameworks: What elements are necessary to promote quality, transparency, and validity in RWE?” at Virtual ISPOR 2020, these recommendations are often fragmented, and pose challenges for sponsors as they navigate different stakeholders’ nuanced definitions of “high quality RWE.”
In our RWE Guidance Watch series, we alert readers to recent, influential RWE guidances issued by standard-setting organizations, and what they mean for biopharma as organizations develop plans for RWE generation. In this entry, we examine the role of RWE in updates to the National Institute for Health and Care Excellence’s (NICE’s) health technology evaluation process.
NICE’s “Changes we’re making to health technology evaluation”
On November 6, 2020, NICE published a summary of its proposed changes to health technology evaluation methods.
NICE periodically assesses its methods to optimize the process and ensure it can support rapid access to clinically- and cost-effective technologies. Within the scope of this process, NICE is considering only updates to its methods for evaluating health technologies, highly specialized technologies, medical technologies, and diagnostics.
This process is separated into two parts:
- Determine if there is a case for changing the current evidence and considerations affecting the methods for evaluations (a process which is under consultation until December 18, 2020); and
- Taking into account feedback from stakeholders, “develop a structured decision-making framework, and include the changes in an updated program manual.”
Below, we share a summary of the key takeaways from this list of suggested changes to NICE’s evaluation methods.
RWE will play an expanded role in health technology evaluation
While NICE’s “general preference for randomized controlled trials (RCTs)” will not change, NICE recognizes the limits of RCTs and is focused on ensuring the evidence it evaluates is comprehensive—and thus includes non-randomized evidence. In line with the Statement of Intent to expand the use of RWE in all NICE guidances, NICE again calls attention to the need for RWE in health technology evaluations.
In the suggested changes for health technology evaluation methods, NICE proposes “a broad refresh…of how the roles of different sources of evidence” are used and an emphasis on how RWE can complement or supplement RCT evidence.
NICE highlights the need to create guidance on:
- How to use non-randomized/RWE evidence in the evaluation process;
- Where RWE can be most valuable, including providing information on the generalizability of RCT evidence to clinical practice, evaluating long-term outcomes not studied in trials, and describing patient groups and the natural history of disease;
- How to assess and report study quality, risk of bias, and confounding; and
- How to present RWE findings.
Work is underway to address the need for clear and concise recommendations on these topics, including through demonstration projects like RCT DUPLICATE and initiatives like the ISPOR-ISPE Transparency Initiative. As NICE’s RWE guidance development progresses, it will be important to evaluate the consistency of recommendations across stakeholders.
Areas where RWE can make a more subtle impact on NICE’s evaluation methods
- Surrogate endpoint validation: With the increased use of surrogate endpoints in drug approvals, the need for validation is also increasing. NICE calls for more detailed description of its “expectations for validation and how to properly account for uncertainty in surrogate relationships.” RWE could play a role in surrogate endpoint validation by evaluating the correlation in surrogate endpoints (e.g., progression-free survival) with patient relevant clinical endpoints (e.g., overall survival) . Groups including the Duke-Margolis Center for Health Policy and Friends of Cancer Research are studying the availability and validity of both surrogate and clinical endpoints in RWD sources.
- Synthesis of RCT and RWE evidence: In order to comprehensively understand the clinical benefit of a health technology, HTA bodies must synthesize evidence from multiple sources using rigorous methods. NICE suggests aligning its methods recommendations to a recent Decision Support Unit publication that lists preferred methods for synthesizing RWE and RCT results, which can support the increased reliance on RWE to supplement RCT evidence.
- Importance of subgroups: NICE recommendations often consider the clinical and cost-effectiveness impact on subgroups of the indicated population, or of the population studied in the RCT. To ensure the subgroup analysis is robust, NICE proposes minor changes in methods recommendations, but RWE can also support in cases where thorough subgroup analyses of the RCT data is not possible. For example, differences in treatment care pathways between clinical practice and comparators are often areas of uncertainty when the RCT study design does not match clinical practice. RWE can be used to study subgroups in the real world and reduce uncertainty in generalizability of the RCT results.
Impact on biopharma
The trend towards increased reliance on RWE in health care decision-making continues to spread across a range of stakeholders, including HTA bodies and biopharma as organizations plan drug development and launch strategies. As a result, organizations’ RWE generation strategies should be incorporated early in both regulatory and value discussions—especially with this push from HTA bodies to adopt RWE in their methods.