The Marketing Authorization was based on data from 1’521 patients that were included in the RCT CLARITY AD covering patients with both, MCI and MD. Primary endpoint in CLARITY AD was the change in the CDR -SB (Clinical Dementia Rating) Scale.

The German HTA Body G-BA assigned ‘Watchful Waiting’ as Appropriate Comparative Therapy (ACT) for MCI and treatment with Donepezil or Galantamin or Rivastigmin as ACT for MD. Based on CLARITY AD outcomes combining MCI and MD patients (as respective heterogeneity tests on the MCI and MD subpopulations were not significant), the HTD is claiming a considerable additional benefit for Lecanemab. Reversely, the Institute for Quality and Efficiency in Health Care (IQWiG) is analysing the two subpopulations separately and suggests no additional benefit, neither in MCI nor MD. In his commentary Thomas Kaiser, the head of IQWiG concludes: ‘This evaluation clearly shows how important an independent evaluation based on all available information is and remains. This is the only way people with early Alzheimer's dementia can make the right decision for them in difficult personal situations’.

Respective data supporting the HTD claim and the IQWiG assessment are displayed in the table. 

* https://www.g-ba.de/bewertungsverfahren/nutzenbewertung/1257/#dossier

From a clinical point of view the publication of the CLARITY AD trial data in the New England Journal of Medicine concludes: ‘Lecanemab reduced markers of amyloid in early Alzheimer’s disease and resulted in moderately less decline on measures of cognition and function than placebo at 18 months but was associated with adverse events’.

Type 2 error in health technology assessment (HTA) would be not acknowledging an (additional) benefit that does exist. In the case of Lecanemab, the published clinical trial data, the assessment of the European Medicines Agency (EMA) and the health technology developer’s (HTD) German HTA dossier conclude that there is a benefit for patients. IQWiG’s assessment however, addressing the two populations (MCI & MD) separately, concludes with no additional benefit for Lecanemab in the two subpopulations – raising the question, if this negative outcome might be carrying a type 2 error.

While a detailed reflection of efficacy in the various patient populations included in i) CLARITY AD, ii) the EMA assessment, iii) the HTD dossier, and iv) in the MCI and MD sub-populations is beyond the scope of this post, the EAA secretariat would like to stress the general risk of type 2 error in HTA assessments that are based on subsets of patients instead of the full and appropriately powered clinical trial data population. In line with the fundamental principles of evidence-based medicine (ebm) an integrative perspective on the totality of best available evidence is required to determine what are the best outcomes for patients and society as a whole, as stipulated in Recital 3 of the EU HTA regulation. Furthermore, as mandated by ebm, integration of the consolidated clinical and patient perspective in addition to the rather technical, data driven, health technology assessments, is critical to prepare for well-balanced societal decision making.

EAA News & Media Posts - Archive

Topical Collection at the Journal of Market Access and Health Policy on EU HTA:

The European Access Academy (EAA) and the Market Access Society (MAS) are editing a Topical Collection at JMAHP focusing on EU HTA, with Jörg Ruof and Mondher Toumi as guest editors. The goal of the Collection is to generate a comprehensive resource consolidating relevant information and diverse perspectives from various stakeholders and a range of focus topics regarding EU HTA.

Access the Collection HERE directly at the journal or find a list of all articles in this collection HERE.