The first crucial point emphasised in the report is the importance of early engagement when companies are planning to submit evidence to HTA bodies based on surrogate endpoints. It is vital for companies to understand precisely what will be required in the submission process. Here are several more critical aspects highlighted in the report:
The move toward using more standardised terminology when describing surrogate endpoints has been highlighted. This includes both how an endpoint is described and the clinical definitions employed. Regarding how we describe an endpoint, they’re suggesting using the framework proposed by Ciani.
Other things that come out clearly in the documentation is the importance of considering the transferability of evidence across different populations when developing models that link surrogate endpoints to target outcomes. Factors such as the population, mechanism of action, disease type, disease stage, and clinical setting must be carefully considered when generalising and broadening the evidence base.
To ensure the appropriateness of this transferability, companies will need to conduct thorough literature reviews to demonstrate how information on the relationship between surrogate and target outcomes is gathered. This review process will need to specify the sources of evidence and justify their relevance to the target population.
It will no longer be acceptable to rely solely on the database the company has access to and claim it as the only valid source of data. This practice has unfortunately been too common in the past but will not be sufficient going forward.
Recommendations for Models developing
The report also provides recommendations on how models should be developed for HTA bodies:
One of the key issues we’re observing is the increasing use of surrogate endpoints in regulatory applications, and consequently, in HTA assessments. There is growing evidence that highlights problems in this area, as we are seeing more submissions based on these surrogates. It’s becoming clear that there are significant inconsistencies in how surrogate endpoints are handled and defined by clinicians, regulators, and HTA bodie. This is problematic.
When we reach the HTA stage, we need to demonstrate not only that the surrogate is clinically appropriate and that the patient will benefit, but also that we can predict the size of that benefit and its impact on the cost-effectiveness of the economic analysis.
So far, the process has not been set up in a way that makes this easy to achieve.
We’ve also noticed major inconsistencies in the quality of the evidence submitted by manufacturers to validate the use of surrogate endpoints, particularly in their economic analyses. We hope that by issuing this guidance, we can provide a clearer signal to manufacturers about what is needed and raise the overall quality of submissions across the board.
This work involved nine HTA agencies, so that's actually quite countries and some of the key cost effectiveness markets within that. There's also work ongoing within Eastbrook looking at producing on a more international scale, with of course very similar themes around the recommendations, a guidance document. So I would say that while not all HTA bodies are aligned on exactly how uncertainties around surrogate outs should be explored, there is a really good level of alignment that more needs to be done to justify, validate and present the uncertainty around the impacts of surrogates in HTA. And then for global companies, I would strongly recommend that taking an early advice on how best to do this will be absolutely critical. And that should be done in a local setting where possible if the regulator and the HTA body in the same room.
The updated NICE guidance on surrogate endpoints provides a critical framework for improving the consistency and quality of health technology assessments (HTA). It emphasises early engagement, standardized terminology, and robust evidence in submissions. Key recommendations include considering the transferability of evidence across populations and ensuring models reflect the entire disease pathway. With input from nine international HTA agencies, the guidelines foster global alignment, offering essential insights for pharmaceutical companies on best practices for using surrogate endpoints in HTA evaluations.
Dawn Lee is a distinguished Associate Professor of Health Economics and Health Policy at the Peninsula Technology Assessment Group (PenTAG). A current lead for an Evidence Review Group and serving as a NICE committee member, Dawn is an exceptional health economist with a track record of over 50 UK Health Technology Assessment submissions and global expertise spanning more than 30 countries.
