By Maxine Bookbinder

August 14, 2018 | An aggressive effort to increase recruitment and participation in Alzheimer’s Disease (AD) clinical trials is underway to attract more volunteers, complete more trials, keep pace with current research demands, and ultimately find promising new therapies.

The National Institute of Health’s (NIH) National Institutes on Aging (NIA), with facilitation by the Alzheimer’s Association, brought together experts from government, private, academic, and industry sectors, as well as people with AD, caregivers, and study participants in a collaborative effort to create the National Strategy for Recruitment and Participation in Alzheimer’s Disease Clinical Research, an effort that strategizes, develops, and outlines innovative methods to help study sites and researchers increase volunteer recruitment.

The effort is an outgrowth of the 2012 National Plan to Address Alzheimer’s Disease, which calls for expanded Alzheimer’s Disease research including plans to increase recruitment, engagement, and enrollment in clinical trials.

The goal, says Heather Snyder, Alzheimer’s Association Senior Director of Medical and Scientific Operations, is “to think about more broadly how to engage communities across the country and increase participation. This needs to be a priority. We can’t stop Alzheimer’s Disease, and we need more volunteers.”

The plan will officially launch in the fall, says Marie A. Bernard, geriatrician and Deputy Director of the NIA. “We anticipate a finished product that will give helpful strategies for recruitment at local, regional, and national levels to other government agencies, medical providers, people with Alzheimer’s, and caregivers. Everyone needs to be more informed and aware of the challenges and opportunities of recruitment.”

Bernard says the plan is designed to “have a truly representative population of people on whom interventions have been tested, to get trials done quickly and efficiently, and that whatever comes from these studies are applicable to everyone, and the studies that look at caregiving can be applicable to a broad range of individuals.”

AD Trial Landscape

NIH currently sponsors in whole or in part about 140 active AD clinical trials. While there is no shortage of trials, there is a critical shortage of volunteers recruited for these trials. According to the Alzheimer’s Association, AD is the sixth leading cause of death of Americans, claiming more lives than breast and prostate cancers combined. Between 2010 and 2015, AD deaths increased 123%. Early diagnoses could save up to $7.9 trillion in health care costs; more than 16 million unpaid U.S. caregivers gave about 18 billion hours of care valued over $323 billion.

Although recruitment and retention difficulties impact the entire clinical industry, AD trials have unique challenges. Different studies require different age requirements and cognitive abilities, ranging from healthy and unimpaired to severely impaired, depending upon the study. While people in cognitive decline require a partner to assist with tasks such as driving and reporting, potential volunteers with no impairment often don’t enroll in AD trials due to a lack of awareness or the stigma of AD.

Perhaps, ironically, one targeted demographic is younger, healthy volunteers, some of whom may have a genetic risk or evidence of pathology on brain scans. Changes in the brain can occur up to 20 years prior to the onset of symptoms, which means that researchers, depending upon the trial, seek volunteers in their 30s and 40s. “We need to get the word out that we need them,” says Bernard, “and to think about the possibility of being involved in trials. We want people to think about it when they don’t have symptoms.”

Stringent eligibility requirements scare potential participants; only 10 – 27% of patients are trial eligible. In some cases, the screening ratio is as high as 10:1. Trials for unimpaired volunteers who might be at risk for AD require gene and biomarking screening and, in some cases, knowing their APOE risk factors. If they discover they have early signs of pathology, “then what is the impact that has on them?” says Bernard. Those who choose to not know results are ineligible for that study. Some trials involve invasive and time-consuming procedures, such as brain imaging with radioactive materials, lumbar punctures, spinal fluid samples, genetic testing, and blood tests.

Such barriers showcase the need for a national initiative and the ability to identify potential participants, says Snyder. In response, the National Strategy suggests increasing awareness among doctors and the general public through education seminars and working with community agencies that cater to individuals ages 45 and older.  While more clinical trial volunteers in general tend to be women, there was a slightly higher number of male volunteers in AD intervention studies. One reason, says Bernard, is that women are most often caregivers who bring male patients into studies, while women who enter intervention studies tend to be older and living alone. “It is imperative,” says Snyder, “that trials are balanced as far as gender, ethnicity, and economic status to better represent their communities.”

Outreach That’s Working

Understanding cultural and ethnic backgrounds can be just as important to recruitment as access to study sites. Researchers must take into consideration the context,” says Bernard. “They must know the community, work in it and become a part of it. There are differences from site to site; researchers must be cognizant of the nuances within different sites. We must focus on the fact that there needs to be diversity in studies.”

Primary care physicians can often be influential figures within communities. It is imperative they know about trials and discuss the importance of participation with patients. However, too many doctors, says Bernard, do not. “They may feel that if there is no viable treatment, then why subject patients to a study? But, if there are no viable trials, then there won’t be any viable treatments.”

For some communities, the entrance point won’t be doctors. For example, outreach must start with the tribal elders in Native American reservations and with church elders in African-American communities. “To be most impactful,” says Bernard, “recruitment must be a local, not a national, phenomenon.”

Innovative outreach approaches to awareness and recruitment are flourishing.  Indiana University implemented a community-based outreach program to increase African-American volunteers. This pilot project uses a collaborative research model to work with a Community Advisory Board, comprised of pastors, retired volunteers, an elder law attorney, and representatives from the State and County Boards of Health, at the Indiana Alzheimer Disease Center (IADC) and the Alzheimer’s Association. They created a research recruitment video targeted to minority communities, identified locations, and designed outreach activities that allow them to work with these communities.

In 2010, the Alzheimer’s Association created TrialMatch, a free and consumer-friendly matching service that matches healthy individuals to trials and AD patients to caregivers.

These programs increased the minority percentage at the IADC from 8.8% to 19% and added 300 African-American volunteers to the TrialMatch database.

The Duke Alzheimer’s Disease Prevention Registry (ADPR) focuses on providing a research-ready registry of individuals ages 55 and over to support clinical trials for Alzheimer’s prevention and treatment strategies. Its cohort has supported 21 studies and currently consists of 4,300 members, including 27% African-American and 73% female.

The Banner Alzheimer’s Institute in Phoenix launched GeneMatch in 2015, the goal of which is to create a pool of willing Alzheimer’s participants, many of whom are already characterized with APOE gene status. The Global Alzheimer’s Platform Foundation (GAP) launched multi-segmented programs in Kansas City, including radio spots, lunch-and-learns with businesses, physician awareness programs, support from local government officials and Blue Cross and Blue Shield, along with other initiatives that increased Kansas City referrals by 200%.

The University of South Florida has a mobile trial unit that travels to specific communities. The University of Pennsylvania studied print and web-based advertisements to determine their impact on readers.

Infrastructure Investments

The National Strategy also cites a need for infrastructure improvements, such as sufficient staffing to successfully complete an 18 to 24-month trial, to respond to participant questions, and to identify eligible volunteers.  “If we have 100 queries but only ten people are eligible, we need to identify those ten,” says Snyder.  Experienced and trained staff is also necessary for procedures such as measuring biomarkers and changes in spinal fluid and doing imaging.

The NIH is seeking proposals on ways to increase diverse community engagement. Although the first draft of the National Strategy is still in development, it has succeeded in raising awareness. “What are the messages nationally we should think about?” says Snyder. “We need to have timelines in moving trials. We need the best strategies to move forward, to know what tactics work and to engage those tactics.”

Researchers can apply to the NIA for grants through a new $3 million funding opportunity, Examining Diversity Recruitment and Retention in Aging Research, to examine the science of Alzheimer’s Disease recruitment research. “There are lots of different approaches,” says Snyder. “Which are the most effective and efficient? When we understand more of the science, then we have to figure out how we can help people who are having significant symptoms, and what interventions they need to help with these and other symptoms.”  The NIA also sponsors a training program for new researchers to focus on health disparities in minority populations as well as the causes, and how to enhance diversity in studies and in the biomedical workforce.

Although there is no specific deadline for proposals or actionable initiatives, Snyder says time is critical.  “We need volunteers. Without them, new drugs will take longer, and we can’t afford to wait.”

After the National Plan launches, the next step, says Bernard, is to review its progress. “This is not a one-and-done sort of thing. It must be monitored to see what needs to be tweaked and to further enhance it.”

Snyder wants to look beyond clinical trials to how these agencies—and perhaps patients’ social supports—can help individuals with AD during different stages of progression. “There are no guidelines for what care should look like.”