The Alzheimer’s Disease‐Health Indices (AD‐HI): Development of Two Novel Outcome Measures for Use in Clinical Trials

Abstract

AbstractBackgroundIn preparation for upcoming clinical trials, there is a clear need for improved clinical trial infrastructure to facilitate therapeutic assessment in Alzheimer’s disease, (AD), mild cognitive impairment (MCI), and related dementias. This research describes the development of a patient‐reported outcome measure, the Alzheimer’s Disease‐Health Index (AD‐HI), and a caregiver‐reported outcome measure, the Alzheimer’s Disease Caregiver‐Health Index (ADCR‐HI). These novel outcome measures were developed using large scale input from patients and caregivers and were designed in accordance with U.S. Food and Drug Administration (FDA) guidelines for use in drug labeling claims.MethodWe first conducted semi‐structured qualitative interviews with individuals with AD, MCI, or dementia and their caregivers to identify potential symptoms of importance to these disease populations. We subsequently performed a cross‐sectional study involving individuals with AD, MCI, or dementia and caregivers to determine the prevalence and relative importance of symptoms identified during preliminary qualitative interviews. Using this data, we developed two outcome measures known as the AD‐HI and the ADCR‐HI. Symptom questions and subscales were selected for the instruments based on their prevalence and importance to the patient populations, their generalizability, and ability to respond to therapeutic intervention. Factor analysis was used to group symptom questions into distinct symptomatic themes of patient health.ResultFifteen individuals with AD, MCI, or dementia and 15 caregivers provided 2,263 quotes regarding the symptomatic burden of AD, MCI, or dementia. One‐hundred and four patients and 329 caregivers participated in a cross‐sectional study to determine the prevalence and relative importance of the most relevant symptoms identified through interviews. The AD‐HI and the ADCR‐HI were developed based on this data and simultaneously measure overall patient disease burden and disease burden in 9 disease specific areas.ConclusionThe AD‐HI provides researchers and clinicians with a valid mechanism to measure disease burden during therapeutic trials involving individuals with AD, MCI, or dementia. Similarly, the ADCR‐HI provides a viable option when a patient can no longer complete a patient‐reported outcome measure on their own behalf. Ongoing steps will further optimize the usability and reliability of these instruments in preparation for upcoming clinical trials.