A Conference Devoted to Better Engaging Clinical Trial Volunteers
Clinical trials, particularly for Alzheimer’s disease, often struggle to find participants fast enough and retain them until the trial is over. As more drugs move into Phase 3, this is increasingly seen as a major bottleneck in the movement toward new treatments. To brainstorm solutions to this problem, about 30 stakeholders from academia, industry, and clinical and advocacy groups met November 1–2 at the Cleveland Clinic Lou Ruvo Center for Brain Health in Las Vegas. They agreed that trials are evolving and that technology plays a role in that process. By harnessing the power of Internet registries and online patient communities, trial sponsors can better reach potential participants. Initiatives have sprung up to reach new populations, especially minorities who are often underrepresented in trials. Speakers also discussed ways to keep people in studies, such as providing incentives and help with transportation to study sites (see part two of this series).
Above all, speakers stressed the importance of listening to patients. Their feedback can inform both the design of the trial and the selection of outcome measures that matter most to patients. In addition, participants often want to be kept in the loop about the results. Since many people enroll in trials for altruistic reasons, trial sponsors should share what was learned so participants can see what their generosity produced, said keynote speaker Freda Lewis-Hall, chief medical officer at Pfizer Inc. Pfizer has started to share trial information, and has received enthusiastic feedback from volunteers about it, Lewis-Hall added.
The conference sparked ideas and produced new collaborations, with the Lou Ruvo Center staff expressing interest in partnering with several Internet registries. However, it remains to be seen if any of these strategies will truly solve the long-standing problem of AD trial recruitment. At the conference’s end, Jeffrey Cummings, who heads the Lou Ruvo Center, said, “What most excited me was the idea of giving patients a voice in clinical trials.”
What Ails Trials?
Enrollment problems are common to clinical trials in all areas of medicine, according to a recent report from Tufts University. Overall, about one-third of sites worldwide fail to meet enrollment goals, and 10 percent fail to sign up any patients. Moreover, the pace of recruitment creeps along, often taking twice as long as projected, the report found. Most sites recruit less than a single patient per month, Cummings noted. This means that recruitment for large trials can drag on for several years.
AD trials face particular challenges. For one thing, as few as 10 percent of AD patients may qualify for a given trial due to strict inclusion and exclusion criteria (see Treves et al., 2000; Grill et al., 2012). Many studies reject people who take certain prescription drugs or who have various co-morbidities, yet people older than 65 take an average of 14 medications per year, and frequently have other conditions such as diabetes, noted Joshua Grill, who leads recruitment at the Mary S. Easton Center for Alzheimer’s Disease Research at the University of California, Los Angeles. Trial sponsors often screen 10,000 potential participants or more by telephone to end up with a few hundred people in a study, noted Robert Berman, who directs clinical neuroscience research at Bristol-Myers Squibb. This translates to a 1 to 2 percent success rate.
In addition, patients who do get into a trial hardly represent the general AD population. Grill noted that enrollees tend to be younger and more educated, and are more likely to be married than the average Alzheimer’s patient. About 90 percent of participants in the United States are Caucasian, despite the fact that minorities such as African-Americans and Hispanics have higher odds of developing AD than do whites. This means study results may not be generalizable to these populations. “Drugs are made for people who participate in clinical trials,” noted Stephanie Monroe, director of the newly launched African American Network Against Alzheimer’s, a branch of the advocacy group USAgainstAlzheimers.
With some 5 million Americans suffering from AD, how could it be so hard to find some 10,000 or 20,000 participants in an expeditious timeframe? Researchers at the meeting agreed it is largely because too few people know about the opportunities to take part in clinical research and the benefits of being in a clinical study. The majority of physicians who see aging patients have never referred a patient to a clinical trial, speakers pointed out, and Lewis-Hall said fewer than 3 percent of Americans take part in studies each year. In the early stages of AD, patients may have no diagnosis yet and are often not referred to memory clinics where they could hear about a trial.
There are also logistical barriers. In the later stages of the disease, caregivers usually decide whether their loved one will participate. They may be overwhelmed with responsibilities already and unable to take on more, or they may worry about the effect trial procedures will have on the patient. Older, less educated, and single patients tend to have little support and struggle with planning and transportation and costs. Also, because relatively few centers in the United States conduct AD trials, their catchment areas limit the pool of potential participants who can reasonably come to a nearby site for repeat visits.
Reaching New Participants
How can trial sponsors raise awareness of their studies and connect with more people who might qualify? Community events can be effective, speakers agreed. The African American Network Against Alzheimer’s, for example, has held events in churches and enlisted the aid of businesses, sororities, and other community organizations to spread the word, Monroe said. The group even sponsored an Alzheimer’s-themed play, Forget Me Not, which featured a black cast and ran in conjunction with other AD awareness events.
Likewise, Dorian Mendoza at the University of Pennsylvania, Philadelphia, noted that the Texas Alzheimer’s Research and Care Consortium recruited more than 500 Hispanic participants through targeted outreach to that community. Several speakers promoted the benefits of holding health fairs with the help of local research centers to let people know about clinical trials. Early memory loss and AD support groups are also great venues for contacting patients, Grill said. Different tactics work best in different parts of the country and for particular patient groups, noted Ed Watson, who developed oncology programs at Acurian in Horsham, Pennsylvania. In densely populated urban areas, print ads on public transit may give more bang for the buck than expensive TV spots, Watson said, while to reach an older demographic in a more rural area, television ads during morning talk shows may be the most cost-effective strategy. Acurian is a for-profit company that specializes in providing patient recruitment and retention programs for clinical trials.
Recruitment through primary-care physicians has been less successful thus far. Most patients say they would consider entering a trial recommended by their doctor, but several speakers said that outreach by trial sponsors to physicians falls flat. Grill described an educational symposium on AD research that drew 2,800 physicians but resulted in only a handful of referrals. A published study found that a community event brought in 69 participants, while targeting physicians brought in none (see Carr et al., 2010). Doctors have little time with patients and are focused on direct patient care rather than trial recruitment, speakers noted.
The best way to use doctors’ offices might be to provide brochures that patients can take home, Monroe suggested. Claire Meunier manages the clinical trial strategies team at the Michael J Fox Foundation for Parkinson’s Research. She noted that in her group’s experience, these materials “go like hotcakes. Patients are hungry for this information.” MJFF recently challenged physicians to hand out pocket cards that encourage patients to sign up on an online registry. The site that registers the most new patients will win a Parkinson’s-related educational event. Since its inception last September, nearly 600 new patients referred from 21 clinics have signed up to be matched with Parkinson’s trials, Meunier told Alzforum.
The Internet stands poised to play an ever-bigger role in trial recruitment. Speakers noted the importance of having a trial website to serve as a “landing zone” where patients can get information. Trial sponsors can reach potential participants through social media, banner ads, and healthcare networks. Currently, Acurian enrolls about 10 percent of its participants, including those for Alzheimer’s trials, through online outreach, Watson said. However, he noted that online strategies are not always cost-effective; sometimes a simple billboard or direct mailings can bring in the same number of participants for less money. For more information on the role of the Internet, see part two of this series.—Madolyn Bowman Rogers.
- Grill JD, Monsell S, Karlawish J. Are patients whose study partners are spouses more likely to be eligible for Alzheimer's disease clinical trials?. Dement Geriatr Cogn Disord. 2012;33(5):334-40. PubMed.
- Carr SA, Davis R, Spencer D, Smart M, Hudson J, Freeman S, Cooper GE, Schmitt FA, Markesbery WR, Danner D, Jicha GA. Comparison of recruitment efforts targeted at primary care physicians versus the community at large for participation in Alzheimer disease clinical trials. Alzheimer Dis Assoc Disord. 2010 Apr-Jun;24(2):165-70. PubMed.
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Turning to the Internet for Alzheimer’s Trial Volunteers
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.
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