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Drug Assessment Uncertainties: HTA Bodies vs. Regulators

August 24, 2021

Blogs Infographics

Written by: Emma Thomas, DPhil Taneesha Chawla

Executive Summary

  • Despite the complementary roles of regulatory agencies and health technology assessment (HTA) bodies in reviewing new drugs, there is substantial divergence in the uncertainties they raise during their respective assessments
  • Manufacturers should consider the concerns of both regulators and HTA bodies at an early stage of development to ensure that evidence is generated to address the needs of both stakeholders
  • Optimization of drug development to support both HTA and regulatory review could result in a streamlined and faster pathway to securing patient access to important new medicines

CBPartners’ Take: A recent study of the review of new medicines by regulatory and HTA bodies has revealed areas of misalignment in their processes, highlighting inefficiencies in the pathway to patient access.


HTA Bodies Raise More Uncertainties than Regulators

Regulatory approval is the first and essential step to market access. However, the second step of HTA review may present a greater challenge to a successful launch. In addition to assessing the clinical merits of a new drug, HTA bodies must also consider their mandates to manage and increase value delivered for the healthcare system.

HTA bodies were found to raise more uncertainties overall in their reviews of new drugs than regulators. As such, HTA body assessment warrants substantial focus and preparation from manufacturers to support the efficient review of their products.

On average, HTA reviews in the EU and USA raised 2.1 and 4.2 more uncertainties respectively per drug than regulators

In 2019 the longest access delays in the EU were for cancer and orphan disease therapies, despite these often being eligible for expedited regulatory review pathways. These pathways are often associated with less robust evidence packages, which may be resulting in greater issues with HTA review. Therefore, the increased scrutiny in terms of number of uncertainties raised by HTA bodies may disproportionately affect access to these populations with the highest unmet needs.

Regulators and HTA Bodies Prioritize Different Uncertainties in Review

HTA bodies and regulators also diverged in the types of uncertainties raised. Safety concerns were almost always flagged by regulators, but only raised in ~60% of cases by HTA bodies, who may rely on risk-benefit reports published by regulators. Conversely, HTA bodies more frequently questioned the relevance of clinical comparators and end points in trials as they probed the clinical benefit supported by the evidence package.

In contrast, concerns regarding trial design covering the population included, lack of reliable sub-group evidence and uncertainties in the translation of benefit from trials to real world practice were similar between stakeholders. Strikingly, the irregularities were very similar between the HTA bodies and regulators in the EU and in the USA.

The divergence in HTAs and regulators’ reviews presents a challenge to manufacturers, who need to tailor evidence generation to address both stakeholders’ concerns. Collaborative programs to support evidence-generation are offered by many regulators to expedite the review process. However, there has traditionally been less incentive for HTA bodies to provide a similar service, although early advice processes are available. In the absence of further coordination between these two essential stakeholders, manufacturers must allocate sufficient resources to cover the different scopes of the dual review rounds to avoid delays in patient access.

Uncertainties Raised by Regulatory and HTA Bodies

Future Considerations for Manufacturers

Manufacturers should consider the priorities of both HTA and regulators in reviews at an early stage of development to ensure that appropriate evidence generation occurs to address all stakeholders’ concerns. Addressing the different scopes of both regulatory and HTA reviews will increase the ability of expedited review pathways to translate to faster reimbursement and patient access.


Read the infographic here.