T 11: Bridging the Gap: The Need for a Paradigm Shift in Clinical Trial Design to Ensure Continued Patient Access to Medicines

Poster Presenter

Richard Macaulay

Senior Director
Parexel Access
United Kingdom

Objectives

This research aims to analyze key reasons for negative appraisals for oncology drugs by national payers in two major markets (NICE in England and IQWiG in Germany) to determine implications for clinical trial design, traditionally aimed to meet the demands of regulators (FDA and EMA).

Method

ORAL PRESENTATION SCHEDULED: Session 1A at 10:10 - 10:20 AM

Publically available NICE guidance documents and IQWiG press releases were screened for any oncology drug receiving negative appraisals by IQWiG or NICE from January 2012 until September 2015 and the key rationale was extracted.

Results

11 IQWiG negative appraisal (defined as benefit assessments where no additional benefit was proven) and 13 NICE negative appraisals (defined as not recommended or only in research outcomes) were identified. The most commonly cited drivers for inadequate demonstration of cost-effectiveness and NICE negative recommendations were: lack of QoL data collection in the trial (5 citations), crossover post-progression confounding OS (3), methodology used to extrapolate OS curves (3), and lack of comparative trial versus the relevant comparator (3). The most regularly cited reasons for IQWiG deeming no proven additional benefit were: pivotal trial was not versus the appropriate comparator (4), lack of significant OS benefit (2), only single arm trials available (2), switching/crossover confounded treatment effects (2).

Conclusion

This research demonstrates that to ensure optimal patient access for putative pharmaceutical products, clinical trial programs must meet the increasing evidentiary demands of payers. Many of the key drivers for a product receiving negative appraisals by NICE and IQWiG were issues that could be addressed through clinical trial design (comparator choice, inclusion of QoL/utility measurements in the trial and post-progression crossover). Nevertheless, clinical trial programs are traditionally designed to meet the demands of regulators and these bodies have recently introduced expedited pathways (EMA adaptive pathways pilot and FDA breakthrough status) enabling access for certain drugs at earlier stages of their clinical development. This trend is in contrast to payer bodies which are increasingly demanding patient relevant comparative benefits that typically come from mature data packages to justify price premiums. Clinical development programs need to be developed to both produce early clinical data that can support expedited regulatory approval where appropriate but also are aligned to payer needs to ensure optimal pricing, reimbursement and market access.