This is part two of a two-part series.
Slow enrollment often hobbles Alzheimer’s clinical trials. At a November 1–2 meeting at the Cleveland Clinic Lou Ruvo Center for Brain Health in Las Vegas, stakeholders brainstormed ways to reach new participants and keep them engaged. Much of the discussion focused on the growing role of technology and the Internet. Internet registries may hold the greatest potential to speed up enrollment, attendees agreed. Many such registries already exist; some quite large, others just springing up. They occupy different niches, with some putting focus on trial recruitment, others on disseminating information, and still others on patient communities.
To support recruitment, the Alzheimer’s Association in 2010 started its TrialMatch service. Patients complete a profile, which a computer algorithm then compares against listed AD trials and returns matches near the person’s hometown. At the moment, the site lists about 165 Alzheimer’s studies and has more than 43,000 profiles, said Keith Fargo, who directs outreach for the association. About one-third of them have been referred to a trial, and according to patient feedback, about 10 percent of them enrolled, Fargo said.
Parkinson’s patients have a similar resource in the Michael J Fox Foundation’s Fox Trial Finder. After finding matches, this service allows either trial sponsors or patients to initiate contact through anonymous messaging, said Claire Meunier, who manages the clinical trial strategies team. Currently 24,000 people have completed profiles, and close to 500 trial sponsors are on board. About 12 percent of people who sign up have joined a trial. Trial Finder is preparing to expand internationally. Meunier noted that sponsors are often skeptical about online recruitment at first, but claimed that once they try it, they love its efficiency. PD trials have recruitment problems similar to AD studies, with 85 percent being delayed and 30 percent failing due to poor enrollment. Strikingly, 80 percent of PD patients say in surveys that they would be willing to participate in trials, but only 10 percent end up doing so, suggesting that there is an untapped pool of potential participants, Meunier said.
The Alzheimer’s Prevention Registry emphasizes education as much as trial matching. This registry started in 2012 and is run by Banner Alzheimer’s Institute in Phoenix. People who sign up receive regular information about AD news and research, and they learn about trial opportunities, said Jessica Langbaum, associate director of the Alzheimer’s Prevention Initiative, which is also under Banner’s direction (see Mar 2011 news story). More than 22,000 people have registered with the prevention registry thus far, the majority of them cognitively healthy and of an average age of 59. Langbaum expects that this registry will act as a shared resource to help academic and industry sponsors of upcoming prevention studies contact people interested in participating in such studies. The Anti-Amyloid in Asymptomatic Alzheimer’s Disease (A4) Trial will be one of the first to use the registry, she noted. (Alzforum is a partner of this not-for-profit registry.)
The online community PatientsLikeMe serves multiple purposes. It provides support communities for people with particular diseases, allowing patients to track their own treatment, response, and side-effect data longitudinally. It also creates a venue for industry to contact potential trial participants and look at patient-generated outcome data (see Jun 2010 news story; May 2011 news story). More than 235,000 people have enrolled at the site; of those, around 8,000 have PD, 6,000 have amyotrophic lateral sclerosis, and 32,000 suffer from multiple sclerosis, said representative Arianne Graham. Other neurodegenerative diseases, including AD, are poorly represented. PatientsLikeMe plans to create services tailored to caregivers who will enter information on behalf of a patient. This might increase the representation of AD patients on the site, and would be applicable to other diseases as well, Graham noted. Many PatientLikeMe members have mild cognitive impairment, providing a pool of people who might be interested in AD prevention trials. A number of pharmaceutical companies have recruited for trials through this site, Graham claimed. The site is free to users, but industry pays to use its data.
Acurian is a for-profit company that specializes in trial recruitment. It maintains a proprietary database of 75 million people who have expressed an interest in research trials, said company representative Ed Watson. Meanwhile, the new National Clinical Trial Network focuses specifically on matching minorities to trials.
Keeping Patients Engaged
Finding potential participants is one-half of the problem. Trial sponsors need to provide incentives for people not only to enroll, but also to stick with it to the end. Dropout rates of around 30 percent are common in AD trials, and wreak havoc with their power and statistical analysis. To retain more participants, researchers should listen to patient feedback and find out what would make trials more practical for them, speakers said. For example, trial participation often imposes burdens on patients and caregivers. Long trials may require 20 or more visits to a medical center, which often can be far away from the patient’s home, noted Joshua Grill, who leads recruitment at the Mary S. Easton Center for Alzheimer’s Disease Research at the University of California, Los Angeles. Caregivers may have jobs, children, or other responsibilities to juggle. Almost half of Hispanic elders live at or below poverty level, and sometimes minority participants can barely afford the added cost of transportation to the trial site, said Dorian Mendoza at the University of Pennsylvania, Philadelphia (see Dec 2008 news story).
To ease the financial burden, even modest financial compensation to participants helps offset their costs and shows respect for their time, said Stephanie Monroe, director of the African American Network Against Alzheimer's, a branch of the advocacy group USAgainstAlzheimers. Something as simple as providing tokens for public transportation keeps more people returning for trial visits, Mendoza said. Some trials provide shuttle service to and from the clinic. Eliminating wait times for appointments can help offset the length of clinic visits, Grill said. Showing appreciation with words is important, too. Grill’s team tells new enrollees, “You are no longer a patient. You are now the most important person on our research team.” As the VIPs, participants are seen immediately. To ease the logistical burden, some trial managers negotiate with their institutions to offer evening and weekend trial visits for working patients or caregivers, or allow patients to collect some data at home, Grill said.
Several researchers described smartphone apps designed to improve patient and caregiver support, or to improve communication between them and trial sponsors. More than half of Americans now own a smartphone, with use high among minorities, said Julia Bernstein at Ginger.io. This technology company has an app that tracks people’s health through a combination of passive recording and input from the user. It is now tailoring this service for AD patients, for example by adding cognitive tests (see Jun 2012 news story; Dec 2012 news story). However, these mobile technologies have not yet been tested in an AD trial environment.
Harness the Wisdom of the Patient
Researchers are learning that to develop outcome measures for drug effects that are more meaningful to the patient, getting information straight from the horse’s mouth can be powerful. PatientsLikeMe recently received a $1.9 million grant from the Robert Wood Johnson Foundation to develop better patient-reported health outcome measures (see RWJF press release). For its part, the FDA has established the Patient-Centered Outcomes Research Institute (PCORI) to enhance communication with patients. “The drug-development system has ignored the role of the patient,” said Freda Lewis-Hall, who sits on PCORI’s board of governors and is chief medical officer at Pfizer Inc. In Alzheimer’s research, as well, an initiative to establish and validate patient-reported outcomes is underway.
Many patients enroll in trials to contribute to the greater good. “I wanted to feel useful again,” said Bob, an AD patient who participated in the solanezumab trial (see Aug 2012 news story). Bob spoke at the conference, disclosing only his first name. His wife said that the trial was a positive experience for them thanks to the warmth and support of trial center staff, who met them at the elevator, drove them to appointments, and took them to lunch. “It became a family, and they made you feel like the most important person in the family,” she said. The advent of new technologies, recruitment strategies, and more open communication may bring the opportunity to take part in trials to a greater number of people in the future.—Madolyn Bowman Rogers.
- Scientists and Regulators Discuss Preclinical AD Trials
- Research Brief: Website Helps People Understand Symptoms, Side Effects
- Led by ALS, Social Networking Comes to Medical Research
- Clinical Trials—Could Participant Amenities Boost Enrollment?
- Patient-Reported Outcomes Win Alzheimer's Challenge 2012
- Tech Revolution: Monitoring and the Power of Real-Time Data
- Phase 3 Solanezumab Trials "Fail"—Is There a Silver Lining?