HTA in Question. Event 1: Evidence Generation: Quality of data for decision-making. 21.10.2021

Health technology assessment (HTA) has always faced an issue with comparators: global randomised controlled trials (RCTs) are often run against comparators that do not represent the standard of care in the jurisdiction conducting an evaluation. For the same reason, populations in the trial might not be generalisable. Indirect treatment comparisons are routinely used by many HTA agencies, which increases uncertainty for decision-makers. In addition, while the methods for conducting indirect comparisons have evolved significantly in the past 10 years, important differences in trial design, measurement, and timing between contemporaneously-approved medicines often make such comparisons problematic or even impossible. Many HTA methodological frameworks rely on modelling of long-term outcomes not available from the trials and the less and poorer evidence base we have at the start, the more uncertainty we are facing with extrapolation.
Over the past 10 years the innovation agenda, pressures from investors, patient groups, policy incentives to accelerate access to new medicines have influenced clinical trial design. Speed of drug development has become a key metric of success. The regulators benchmark their performance on the number of medicines approved as it is not within their remit to consider the value that these medicines bring to patients and society.
In oncology and rare disease settings, in particular, we are seeing an increased number of approvals based on single-arm Phase II trials and unvalidated surrogate endpoints. A requirement from the FDA of 2 identical Phase III trials is no longer the norm. In general, trial duration and trial sizes are shrinking resulting in fewer data points and less robust evidence for reimbursement decisions. Despite an increase in the collection of quality-of-life data in clinical trials over the past decades, we are still far from this being a routine practice.
The issues highlighted above are increasing in volume and impact. There seem to be no signs of improvement on the quality of evidence requirements, pushing health systems to resolve uncertainty through price discounts, managed access agreements and the use of real-world evidence.