Inspiration for Canada: Ensuring Access While Reducing Risk
October 31, 2023
Having lived and breathed managed access for much of his career, NICE’s Thomas Strong is just the person to encourage Canada to explore such agreements.
Thomas Strong is the Interim Associate Director for Managed Access at the National Institute for Health and Care Excellence (NICE), the UK’s health technology assessment (HTA) agency. NICE helps facilitate optimal and timely care to patients, while ensuring value for the taxpayer. Thomas joined NICE in 2016, starting as a technical analyst and progressing to HTA adviser, a role that saw him develop managed access programs for cancer medications. His current position puts him at the helm of NICE’s Managed Access Team, which is responsible for identifying candidates for managed access agreements (MAAs), delivering data collection agreements, and monitoring existing MAAs. In this conversation, Thomas shares his deep experience with MAAs and identifies key learnings that could help Canada move forward in the MAA space.
How do you define managed access and what is its rationale?
Managed access in the UK is a time-limited arrangement to give patients early access to promising new drugs. The process helps manage the uncertainty around evaluating a new treatment and ensures the NHS [National Health Service] is paying a cost-effective price during the managed access period. In truth, managed access is a compromise with reality: in an ideal world, we would routinely list all newly approved drugs. In the real world, where new therapies are sometimes approved on the basis of phase 2 trials or immature data, the evidence may be too uncertain for NICE to determine whether a new medicine is a good use of NHS resources. An MAA enables us to gather further evidence to make a final decision on cost-effectiveness, while also allowing patients to access potentially life-changing medicines by commercially sharing the risk with our industry partners.
What is the context for the establishment of MAAs in England?
In 2021, the UK spent over 17 billion pounds on health technology, of which a sizable proportion goes to cancer treatments, and there is a constant influx of cancer drugs coming down the pipeline. This means we have to balance two priorities: getting innovative drugs to patients as quickly as possible while ensuring value to taxpayers, who fund the NHS. We need to remember that, if NICE recommends a treatment that ends up not being cost-effective, it would be at the expense of other, higher-value treatments. Our two managed access funds – the Cancer Drugs Fund and more recently the Innovative Medicines Fund – grew out of these priorities. Together, these funds provide 680 million pounds per year to spend on innovative medicines and on expediting access to these drugs while managing risk.
What does “managing risk” look like?
It's important to be explicit about the risks to the different partners: the HTA body, the payer, but also industry and patients. For instance, in our original managed access process, treatments could be withdrawn from patients if NICE gave a negative recommendation. That risk was being borne by patients and it caused them a lot of anxiety. When we developed the Innovative Medicines Fund, we made it clear that the drug company, not the patient, would bear the risk by continuing to pay for treatments that were deemed to not be cost effective at exit.
How do you identify candidate drugs for an MAA, and how long does the process take?
In most cases, we enter into managed access because a promising drug is entering the market with immature data – but there can be other reasons, such as the clinical trials not being representative of NHS clinical practice. I should emphasize that MAA is only suitable for really promising new drugs. If we’re worried that a drug may not work, managed access isn’t the right vehicle for it. As for timelines, we seek to get from the decision-making committee to an MAA in about 35 days. It’s an ambitious timeline that requires us to do a lot of work upstream and to monitor the entire pipeline.
“Managed access is only suitable for really promising new drugs. It allows us to balance two priorities: getting innovative drugs to patients as quickly as possible while ensuring value for taxpayers.”
How do you set drug pricing during the MAA period?
Drug prices are negotiated between NHS England and the company, with the parameters informed by the uncertainty and risk identified by NICE. In England we like to keep it simple, so we aim for a straightforward price discount during the MAA period. A discount is easy to transact and to negotiate. The key difference, compared to routine listing, is that this discount can apply to the specific indication that is entering managed access, rather than across all indications a medicine can be used for. Once the price is set, we enter the managed access period: patients get access, data is collected, and hopefully the evidence collected sufficiently resolves the uncertainty. At that point, as part of the commercial agreement process, a new price can be offered. If the data determines a drug to be more cost-effective than anticipated, industry has the opportunity to change the price to reflect that.
How long does the MAA period generally last?
We want to collect data as quickly as possible – within 5 years is our limit. We don't want to keep treatments suspended in managed access forever. We have had some drugs move through a MAA in as little as 6 months, while others have pushed right up against our 5-year limit. Our median has been 3 years.
Has the effort to establish MAAs been worthwhile? Have these agreements fulfilled their intended benefits?
We have seen 55 cancer drugs come through the MAA process, and 28 of them have exited from managed access – in most cases proceeding to routine listing. In some cases, the data resolves the uncertainty, but reveals that the medication is not as cost-effective as the drug company expected. This doesn’t mean the process wasn’t a success. On the contrary: it affords a renegotiation point to enable a transition to routine listing.
NICE and the NHS have recently established some “Day Zero” early access agreements. Is this a goal for NICE, and how did you make that happen?
With a Day Zero agreement, a product is listed on the day it receives regulatory approval. It is definitely a goal. NICE has designed its methods and processes to align with the regulator, which means doing a lot of work upstream. To do this, we need a framework for streamlined entry, which means coordinating with other policymakers. Managed access doesn’t occur in a vacuum: a lot of other policy developments must fall into place to make it possible. For example, we have the Early Access to Medicines Scheme, whose purpose isn’t about value: it’s about unmet need and access, and it happens before NICE evaluation.
“Managed access doesn’t occur in a vacuum: a lot of other policy developments must fall into place to make it possible.”
What role does real-world evidence [RWE] play with MAAs?
To date, ongoing clinical trials have been the key driver for resolving uncertainty, rather than RWE. Why would this be? Let’s say we already have 5 years of data from a clinical trial, with 3 more years to go. In such a case, the RWE will never catch up to the data from the ongoing trial. That said, RWE is being used with increasing frequency and is often the only source of evidence to resolve uncertainty for rare-disease drugs. Indeed, some rare-disease drugs have had such good results at phase 2 that clinicians consider it unethical to delay access by requiring Phase 3 trials. In such a case, RWE fills the evidence gap during a managed access period.
What are some best practices for generating RWE?
Focus on the data that matters most. With RWE, it’s tempting to try and collect everything. This has a real risk attached to it – namely, that you don’t actually collect the data that would make a difference to decision-making. Also, there is a real and often underestimated burden attached to collecting, analyzing and using real-world data.
Once the evidence is generated, how does NICE manage the reassessment of the drug within the MAA?
With innovative medicines continually being introduced, we recognize that the landscape may change. We need to look at the totality of the evidence and make decisions that are relevant for people now, not validate a decision that is several years out of date using just the evidence collected within managed access. That’s why it’s critical for NICE to be involved at both the front end and exit of MAAs, because we want to make sure we have cost-effective medicines in the NHS at all points in time.
How do you ensure a smooth exit from MAAs?
Above all, you need to be clear on what the exit process will look like. Predictability is key for all stakeholders, and you don’t want to be changing things all the time. If you don’t set up clear expectations, you’re not giving industry the best opportunity to prepare effectively. You also want the exit to be as streamlined as possible, which means you need to work backwards to understand how you're going to transition into routine listing.
“The exit process for MAAs needs to be clear. If clear expectations are set, we are giving industry the best opportunity to prepare effectively.”
What role should industry play in MAAs?
We engage upstream, so we start talking to companies in advance of an anticipated MAA. During the managed access period, we involve and regularly meet with patients and clinicians, and possibly other stakeholders such as registries and industry, to ensure we are proceeding according to plan and collecting the data needed to resolve the uncertainty. When RWE is involved, we often need to course-correct during the evidence generation period. Regular touchpoints with industry can help us ensure the RWE is fit for purpose and will support a treatment’s value proposition, which enables us to successfully exit the MAA period.
What tangible next steps would you recommend for us here in Canada, to help ensure timely access to novel therapies with uncertainties?
Identify drugs that may be suitable for a MAA early on, so you can get the process rolling in a timely manner. Aim to streamline and standardize the entry and exit process for MAAs to set clear expectations for all stakeholders. And keep exploring the potential for RWE to resolve uncertainties. The advantage of RWE, compared to clinical trials, that it reflects the realities of actual use within a health system. But it’s a double-edged sword: RWE can be messy and complex to analyze. Keeping it as simple as possible reduces your risk. Just because we have very complex new medicines doesn't mean we can't have simple solutions.