The Value of Pre-Screening in the Alzheimer’s Prevention Initiative (Api) Autosomal Dominant Alzheimer’s Disease Trial

Abstract

The Alzheimer’s Prevention Initiative (API) Autosomal Dominant Alzheimer’s Disease (ADAD) trial evaluates the anti-amyloid-β antibody crenezumab in cognitively unimpaired persons who, based on genetic background and age, are at high imminent risk of clinical progression, and provides a powerful test of the amyloid hypothesis. The Neurosciences Group of Antioquia implemented a pre-screening process with the goals of decreasing screen failures and identifying participants most likely to adhere to trial requirements of the API ADAD trial in cognitively unimpaired members of Presenilin1 E280A mutation kindreds. The pre-screening failure rate was 48.2%: the primary reason was expected inability to comply with the protocol, chiefly due to work requirements. More carriers compared to non-carriers, and more males compared to females, failed pre-screening. Carriers with illiteracy or learning/comprehension difficulties failed pre-screening more than non-carriers. With the Colombian API Registry and our prescreening efforts, we randomized 169 30-60 year-old cognitively unimpaired carriers and 83 non-carriers who agreed to participate in the trial for at least 60 months. Our findings suggest multiple benefits of implementing a pre-screening process for enrolling prevention trials in ADAD.

Sex differences in cognitive resilience in preclinical autosomal‐dominant Alzheimer's disease carriers and non‐carriers: Baseline findings from the API ADAD Colombia Trial

“…Our sample included more females overall, and more female PSEN1 mutation carriers. This is possibly a recruitment bias, as previously documented, 63 whereby males were more likely to fail pre‐screening requirements, particularly due to substance abuse. Moreover, female PSEN1 mutation carriers were younger (1.8 years) than male PSEN1 mutation carriers.…”

Modifiable Barriers for Recruitment and Retention of Older Adults Participants from Underrepresented Minorities in Alzheimer’s Disease Research

“…Finally, economic constraints [ 72 ] and opportunity costs in the form of lost wages, coupled with lack of any financial compensation for their time [ 67 ] may also negatively impact recruitment efforts. A recent analysis by Rios-Romenets and colleagues [ 74 ] suggests nearly half of prospective, high-risk participants decline participation, largely due to factors related to study burden, including the protocol itself, as well as travel and work burden.…”

Barriers to Alzheimer Disease Clinical Trial Participation in a Minority Population

“…Previous research into barriers to clinical trial participation found that economic, structural, and logistical obstacles negatively impacted recruitment efforts, with examples including financial burdens, time constraints, and transportation inconveniences (Bonk, 2010; Clark et al, 2019; Clement et al, 2019; Cox et al, 2019; Graham et al, 2017; Heller et al, 2014; Indorewalla et al, 2021; Jefferson et al, 2011; Largent et al, 2018; McDougall et al, 2015; Rios-Romenets et al, 2018; Vaswani et al, 2020; Young et al, 2015). A lack of participation from key groups within the US population affects the generalizability of trial results, effectiveness of therapeutic agents, and equity in the provision of health care (Coakley et al, 2012; George et al, 2014; Indorewalla et al, 2021; Kwiatkowski et al, 2013; Rivers et al, 2013; Swanson and Bailar, 2002).…”

“…Even when individuals were interested in participating in clinical trials for altruistic or personal reasons, they referenced similar logistical, financial, and psychosocial barriers that dissuaded them from enrolling (Cox et al, 2019; Jefferson et al, 2011). Such barriers were often cited as including, but not limited to, opportunity costs in the form of lost wages, lack of financial compensation for their time, potential health risks, lack of adequate transportation, prolonged study durations, and lack of access to health insurance (Bonk, 2010; Clark et al, 2019; Clement et al, 2019; Cox et al, 2019; Graham et al, 2017; Heller et al, 2014; Indorewalla et al, 2021; Jefferson et al, 2011; Largent et al, 2018; McDougall et al, 2015; Rios-Romenets et al, 2018; Vaswani et al, 2020; Young et al, 2015). These impediments to clinical trial enrollment are especially important for diseases like AD, which has ethnicity-dependent pathophysiology, thereby indicating the importance of diversity in clinical trial participation (Howell et al, 2017; Morris et al, 2019).…”