Alzheimer’s disease (AD) is a complex disease with multiple risk factors, which can also complicate clinical trials for new therapies. The need for large sample sizes, long trial durations to capture disease progression, and intricate eligibility criteria mean that clinical trials for AD therapeutics often take longer and are more expensive than trials for other conditions. In fact, it takes approximately 13 years for an AD therapy to progress from preclinical studies to regulatory review.
That’s why it’s particularly exciting that, after almost 20 years of no new drug approvals, therapies such as ADUHELM® and LEQEMBI®, both disease-modifying drugs (DMDs), have made it from the lab to market. In addition, 76% of the 164 trials assessing 127 drugs for AD listed in clinicaltrials.gov are DMDs. The future looks bright for AD treatments.
However, AD drug development is still considered to be higher risk in terms of both clinical and commercial success than other therapeutic areas, which might explain why there are fewer trials and fewer drugs listed on clinicaltrials.gov now than in 2023 and previous years. Strategies to overcome challenges in recruitment, enrollment, retention, and data collection in AD trials are needed to streamline clinical trials and ensure we can get new treatments to the people who need them.
Recruitment is often slow
Slow recruitment in AD trials is a commonly reported barrier to clinical trial completion. Much of this is associated with a lack of awareness about AD and its symptoms as well as about clinical trials. Memory loss and other cognitive impairments are considered a normal part of aging, meaning that they are often not discussed with family members or physicians until the symptoms are pronounced. At the same time, many people fear a dementia or AD diagnosis and might initially avoid discussing their concerns. It’s estimated that only 14% of people who could be eligible for an AD clinical trial ever even reach the healthcare system for symptoms related to AD. This not only delays healthcare but also means that individuals who do present to clinical trials have more severe disease.
Many AD diagnoses occur after the individual is experiencing observable symptoms, which might mean they are ineligible for studies of DMDs. Even if they are, a lack of awareness of clinical trials in general, about specific AD trials, and about who is eligible to participate limit exposure to research opportunities. For example, being able to offer their patients clinical research opportunities was viewed as a benefit of early diagnosis by <40% of primary care physicians (PCPs)in a recent survey.
Mike and Susan O’Brien became involved in AD clinical research only after seeing a neurologist at JEM Research Institute, a Headlands Research site.
Strategies to improve recruitment
Education for individuals, communities, and healthcare professionals is an important first step to improving recruitment. At Headlands Research, we’ve found success in conducting lunch and learns with physician groups as well as educational sessions within the community, such as at community centers and local health fairs. We establish bidirectional communication channels, inviting members of the community and healthcare professionals to contact our sites with questions about ongoing trials.
Through these avenues, there are opportunities to seek feedback about barriers to participation such as transportation, site hours, and compensation in order to strategize about how to overcome those barriers.
Establishing referral pathways for PCPs and other healthcare professionals to provide their patients with opportunities to undergo free cognitive assessments can be an effective way to recruit participants. Advertising these assessments at local health fairs and community sessions improves public awareness. After screening, eligible individuals can be easily matched with available clinical trials, presented with the trial information, and given the choice to participate — increasing recruitment rates while benefiting public health.
Screen failures result in slow enrollment, and burdensome study procedures compromise retention
Screen failure rates for mild AD trials reach an average of 44%, extending trial timelines and adding considerable cost. Screening procedures such as neurocognitive testing, imaging (MRI and PET), and CSF testing are time-consuming and expensive, representing 50% to 70% of the total per-participant costs.
In addition, strict eligibility criteria that exclude individuals with comorbid conditions limit the population from which to enroll. This is especially true given that older adults represent the majority of individuals with AD and often have other conditions such as cardiovascular disease and diabetes and use a higher number of prescription medications — all of which are typical exclusion criteria.
Other barriers to participation and retention include long study visits, logistical barriers such as distance to study sites and transportation challenges, and a misunderstanding about the risks associated with participating. Research participation can be burdensome for both the individual with AD and their caregivers or family members, especially as most studies require that a support person be present during the visits.
Strategies to improve enrollment and retention
Considering broadening the eligibility criteria to include individuals with comorbid conditions or high prescription drug use might require more planning to discern between drug-related cardiovascular events, for example, but would allow greater participation, especially from under-represented populations such as racial/ethnic minorities. We discussed the importance of designing AD trials to maximize representativeness in our previous blog post.
Offering wrap-around services such as support groups for both the individual with AD and their caregiver can help them feel like they’re part of a community, more than just a research subject. This not only enriches the research experience but also encourages word-of-mouth referrals to others within their social groups.
Mike and Suzanne shared their positive research experience with others within their community.
Streamlined recruitment, enrollment, and retention can accelerate clinical trial timelines
Because AD clinical trials often need to demonstrate beneficial effects on cognitive, behavioral, and functional endpoints for regulatory approval, long treatment periods and large sample sizes are typically required to detect a clinically meaningful change. For DMDs, demonstrating a treatment’s ability to slow disease progression can also require years. However, fostering relationships that encourage referrals, minimizing screen failures, and creating a positive research experience can shorten trial timelines through faster recruitment and enrollment and by minimizing drop-outs throughout the study.
Contact us to learn more about our site network’s decades of experience recruiting and retaining representative populations for Alzheimer’s disease trials.