Based on a collection of data from clinical trials in Alzheimer disease, the best way to represent and translate the findings to meaningful benefits is through the use of multiple frameworks.
In recent analysis on published research, presented at the 2023 Alzheimer’s Association International Conference, July 16-20, in Amsterdam, the Netherlands, results show that multiple frameworks better represent and translate findings from clinical trials in Alzhiemer disease (AD). This finding suggests that there should be more expanded data, analyses, and frameworks for effectively defining and translating clinically meaningful patient-centered benefit for providers and patients in the AD field.1
Investigators concluded that multiple frameworks better represent the challenges and opportunities presented in clinical trials in a multidimensional way as they have more face-valid and patient-centered representations that can resonate more with AD stakeholders. These frameworks include expanded outcomes such as neuropsychiatric symptoms, socioeconomic burden, patient- and caregiver-reported outcomes, complementary analyses, and conceptions such as predictive benefit and cumulative benefits.
“Clinical trials in AD are designed and powered to detect treatment impact on validated research outcome measures necessary for regulatory approval. However, what constitutes a clinically meaningful benefit, how to define, measure and translate it from the results of clinical trial results to multiple stakeholders, including clinicians and patients requires better clarification,” author and principal investigator Alireza Atri, MD, PhD, director of the Banner Sun Health Research Institute, wrote.1
In this analysis, Arti et al reviewed a combination of recent publications (Assuncao, Sperling, et al. Alz Res Therapy 2022; Petersen, Aisen Andrews, Atri, et al. Alzheimers Dementia. 2023 in press) and developments in AD therapeutics. The aim of this research was to establish an overview of the treatments and of the frameworks used to translate AD clinical trial findings to meaningful benefits. This was conducted with consideration of the expectations, definitions, challenges and opportunities that multiple stakeholders may resonate under. The stakeholders acknowledged in this research included the patients, the patient care partners and their providers.
During the review of the clinical trials, rational for realistic expectations of putative AD disease-modifying treatments (DMTs) were inquired, including expectations of not improving symptoms but of slowing disease progression and modestly moderating between-group clinical decline, treatment compared with placebo. Also, the definitions suggested to represent clinically meaningful benefits were evaluated.
Arti also explored the representation of thresholds such as with confusion, misunderstanding or misinterpretations for meaningful in-patient progression. Additionally, this part of the analysis included investigating recent misinterpretation of necessary thresholds to determine meaningful group-level differences and having a collection of the misguided expectations for clinical meaningfulness presented in DMT clinical trial findings.
Looking further in the research, Atri also assessed the confounding minimal detectable change and utilization of between-group differences such as in assessing outcome of efficacy. This was explored upon the notion of defining minimal clinically important differences in an individual in-patient change in the assessment of the outcome. Arti noted that the in-patient change thresholds are not intended for the assessment of the meaningfulness in the differences between group-level changes over time. Although, he noted, that it might represent meaningful in-patient trajectories through complementary analyses such as with responder and progressor research.