As innovation in health care advances—and the associated costs escalate—payers are struggling to contain drug prices. To help prioritize spending, payers have leveraged health technology assessment (HTA) agencies to systematically evaluate the effect and impact of technologies—including medical devices, medicines, vaccines, procedures, or other interventions to solve health problems. 

The speed of innovation has also posed challenges; although regulators have created pathways to approve drugs more rapidly when they address unmet medical needs for serious conditions, the HTA process has been slow to adapt to the uncertainty inherent in these pathways for new, innovative therapies. For example, some life changing therapies have been approved based on surrogate endpoints and without a head-to-head comparison with the standard of care, thus leading to uncertainty in long-term clinical outcomes and efficacy versus current treatment options. 

For this reason, a shift has commenced from health technology assessment to health technology management, where drugs are periodically evaluated to determine their role in the changing landscape and within the fixed health care budget. 

Shifting from health technology assessment to management

Most HTA agencies employ a strategy to assess the clinical—and in most cases, the economic—value of a drug once it receives regulatory approval, then they make a recommendation on whether to reimburse the drug. This decision typically remains constant throughout the product’s lifecycle, as most agencies do not have a formal process to reassess drugs as new therapies come to market and the landscape evolves. As a consequence, spending on reimbursed drugs builds year over year, which is not sustainable. 

HTAs are employing a number of strategies that shift their focus from one-time drug value assessment to management through periodic reviews, with focus on how the drug is performing in the current landscape. As HTAs navigate this shift and evaluate how drugs perform in the current clinical landscape, real-world evidence (RWE) will emerge as an essential tool in health technology management. 

Increasing coverage with evidence development 

With accelerated regulatory approvals—for which regulators can accept Phase II evidence from biopharma to more quickly approve therapies for serious medical conditions that fill an unmet clinical need—leading to increases in clinical uncertainty at the time of the assessment, HTA agencies are responding with reimbursement conditional on additional evidence development. These types of agreements allow for reimbursement of the drug for a set period of time while new data is collected to address outstanding clinical and economic questions at the time of launch. Once additional data is collected, the drug will be reassessed to determine its place in the current treatment landscape, and disinvestment is possible depending on the updated results. 

Two prominent examples of these types of schemes are the Cancer Drugs Fund (CDF) in England and conditional funding in the Netherlands. 

The National Institute for Health and Care Excellence (NICE) has the option to recommend the use of a cancer drug for temporary funding (up to two years) in England through the CDF. CDF funding is available in cases where there is plausible potential that the drug will satisfy the criteria for routine reimbursement—if it is cost-effective, for example— but where there is currently uncertainty in clinical effectiveness. A 2018 study showed that since 2016, 19 cancer drugs or indications have been issued temporary funding through the CDF. 

Similarly, the National Health Care Institute (ZIN) in the Netherlands has been implementing conditional funding schemes since 2006, granting funding to 49 drugs. They focus on expensive hospital drugs, for example trastuzumab for the treatment of early breast cancer with increased HER2+ expression, and allow a four year window for continued evidence development to address uncertainties in clinical and cost-effectiveness. 

In both the CDF and ZIN’s cases, RWE has so far been underutilized in evidence development frameworks, but has substantial potential to address both clinical and economic uncertainty in the future. 

With the CDF, the majority of drugs and indications assessed were awaiting results of Phase III randomized controlled trials (RCTs). RWE was only requested by NICE in three of the 19 approved instances. 

Given the main sources of uncertainty listed in the 2018 study for these drugs are related to real-world outcomes—clinical effectiveness, applicability to U.K. clinical practice, and trial design issues, to name a few—there is an opportunity to leverage RWE to demonstrate how drugs perform in real populations. With NICE’s focus on incorporating RWE in their future guidance development, we expect to see an increased reliance on RWE use in these schemes. 

In the Netherlands, RWE is often requested, though due to infrastructure challenges (e.g., time and effort needed to set up registries for data collection) and methodological concerns with drawing effectiveness conclusions from RWE, the impact of RWE has likely been limited. Today, as global regulators, biopharma companies, and HTA agencies shift toward investment in real-world data (RWD) and RWE, there is potential for RWE to have substantial impact on these coverage with evidence development decisions in the Netherlands. 

The need for reassessment

When a new product launches, HTA agencies are challenged by a lack of RWE to determine clinical comparative effectiveness and cost-effectiveness of the new technology. HTA agencies must rely on RCT data—which often doesn’t show drug effectiveness in real clinical practice—and extrapolation methods to determine reimbursement. The ability to reassess a therapy within the patient population and clinical pathways following market access is essential to understanding the actual effectiveness and benefit to the health system. And reassessment is a necessity for health technology management in today’s dynamic, ever-changing health care landscape.  

However, only a few HTA agencies currently reassess drugs on a regular basis. For example, in France, Haute Autorité de Santé (HAS) reasesses all drugs approved by French regulators every five years to determine if the added benefit and actual benefit of the drug has changed. 

HAS has used RWE in this reassessment process: The IMI GetReal project evaluated RWE results submitted in 50 different drugs reassessments, and found that HAS primarily requests RWE to evaluate effectiveness. When RCT findings from the initial reimbursement assessment were supported by RWE results from the reassessment, HAS was less likely to downgrade the actual benefit and clinical added value decisions from the previous assessment. Meaning that the RWE confirmed the drug’s place in the clinical pathways and the important benefit of the therapy. 

In line with the French value reassessment example, we are seeing an increase in the number of HTA agencies proposing reassessment methodology. For example, in Canada, there is no standardized process for reassessing drugs after initial reimbursement approval, but the Canadian Agency for Drugs and Technologies in Health (CADTH) has laid out plans to develop a process in the 2018-2021 CADTH strategic plan. Similarly, the Institute for Clinical and Economic Review (ICER) in the U.S. has announced in its 2020 Value Assessment Framework update that it is developing a process to determine if new evidence, including RWE, has been amassed to warrant a reassessment of their initial review.  

Preparing for the shift

With the help of new strategies around reimbursement with continued evidence development and reassessment of drugs after market access, HTA agencies are better prepared to manage the drug approval landscape and control health care spending. 

RWE will likely play a more prominent role in these strategies in the future. Biopharma can prepare by proactively creating RWE generation plans after product launch to help meet conditional reimbursement and reassessment requirements in their coming work with HTA agencies.