OBJECTIVES: Alzheimer’s disease (AD) is most common cause of dementia worldwide including Europe. Prevalence of AD is expected to increase substantially in next decade and currently approved interventions only provide symptomatic improvement with an unmet medical need. This study aimed to assess positioning of ongoing clinical trials to evolving HTA evidence needs in AD.

METHODS: Clinicaltrials.gov was searched for interventional trials in last 10 years (for landscape assessment) followed by review of literature (Embase^®) for identifying HTA considerations in AD.

RESULTS: In total 150 clinical trials in AD were identified, of which ~50% evaluated disease-modifying therapies (DMT), while remaining evaluated cognitive enhancers, transcranial therapies, or agents relieving symptoms like anxiety and depression. Twenty-six DMT were evaluated in early/mild AD (26 agents) with 10 agents progressed to late stage phase II/III trials expecting launch by 2025 and 5 agents (TRx0237, E2609, ALZT-OP1, Crenezumab, and Gantenerumab) expecting launch by 2021. Impact on cognition was the majorly assessed outcome (using ADAS-Cog and MMSE) followed by QoL and functionality outcomes. Nearly 50% of DMT trials evaluated QoL, however, caregiver QoL assessment was limited (4 trials). Similarly, limited (five) trials assessed resource utilization and correlation between disease stages and outcomes.

Of 849 hits obtained searching literature for AD HTA considerations, 8 studies were included, of which latest was ROADMAP publication. ROADMAP reported partial applicability of existing HTA experience to newer therapies and need for validated and accepted outcomes for HTA process. Our evaluation of ongoing trials indicated that validated outcomes measured cognition and QoL, however, evidence needs for modelling assumptions like correlation between disease stages and outcomes and caregiver QoL were less frequently addressed.

CONCLUSIONS: Possible advent of DMTs based on trials using validated outcomes for assessment is indicative. However, there is need to fill evidence gaps related to long-term impact on patients and caregivers.