For Enroll-HD, signing up new volunteers is only the start. The most valuable information gathered by the study will come from collecting data on the same people followed over a long period of time, to track and compare changes that take place over years.
For that reason, retention—helping people stick with the study—is just as important as signing them up to begin with. “In Enroll-HD we want to collect good data to get a good portrait of HD,” says neurologist Tiago Mestre, assistant professor at the University of Ottawa and medical director of Enroll-HD. “For that we need to know how things change over time.”
Enroll-HD is also intended to be a platform to enable further research and clinical trials of drugs—studies that require good data collection and consistent participation. (For more about this, read the article “Enroll-HD as a Platform”.) Researchers want to be able to track people’s motor performance and cognitive abilities, for example. And they want to understand how sleep or diet affect quality of life and how the disease progresses over time. The only way to get that information is if people come back repeatedly.
There are a lot of reasons people might not come back. They might lose interest in the study, or they might move, or they might become too ill, either with HD symptoms or another condition. A study site might have inconvenient appointment times, or might not do enough follow up to remind participants when the time approaches.
“If you don’t retain the patients, you’ll be losing information.”—Tiago Mestre, medical director of Enroll-HD
In 2016, Enroll-HD has been up and running for four years, and thousands of people have returned for their third and fourth study visit. Retention is running at about 80 percent overall so far, which is pretty good for a study like this. So far, there’s no obvious trends, says James Moyer, project manager at Quintiles, the contract research organization that helps coordinate Enroll-HD: bigger sites do just as well as smaller ones, and most countries are comparable.
Over time, it’s natural for some people to drop out. But it’s essential that this number doesn’t dip too low. “If you don’t retain the patients, you’ll be losing information,” says Mestre. If many of the people who drop out leave for the same reason, it can weaken the whole study.
For example, if many Enroll-HD participants whose symptoms get worse very quickly drop out, then the study will be biased. That is to say, it won’t be representative of the overall population. And it won’t capture what’s different about those people from others whose symptoms progress more slowly. All that information may be crucial to future studies, such as clinical trials.
A good start
It’s up to the clinical site team to make sure that people keep coming back, and they all have different tactics.
Setting expectations for participants early on is important so that people know what’s required of them, and are aware of the fact that there’s no end date for a study like Enroll-HD—people are encouraged to stick with the study as long as possible. “It starts with the message that sites give to patients when they enroll in the study,” says Moyer. “That’s critical— setting the expectation that this is a long-term study. Having that long-term buy-in and commitment is important.”
Getting the first visit off to a good start by establishing a rapport—not just focusing on collecting data—might be the single most important thing site staff can do, says Paul McCann, study coordinator at the University of Alberta in Edmonton. “If the first visit goes swimmingly and you hit it off, they’ll come back,” he says. At the Edmonton site they aim to be as flexible and understanding as possible, and make sure that participants are comfortable. “We always say: let us know if you need a break, a glass of water,” he says. “These are human beings, not a 9-digit ID number.”
Along the same lines, it doesn’t work to try to convince people who aren’t ready to participate in research. People need time to come to terms with the diagnosis, says Laura Paermentier, clinical research coordinator of the New Zealand Brain Research Institute in Christchurch, on the South Island of New Zealand .
Personal relationships and a broader sense of belonging to the HD community are also a major draw. “Sites often have a longstanding history with the participants, they’ve been doing clinical care for 20 years, knew the father and grandfather, and are now treating the current generation,” says Moyer.
At the New Zealand Brain Research Institute at University of Otago, the Enroll-HD team is just two people—Paermentier and neurologist Tim Anderson. Participants seem to like the “consistency of care,” says Paermentier; they like the fact that the same staff is there from year to year. “There is always something positive to say, regardless of the stage of the disease,” she says. “We take interest in people’s lives, we get to know their hobbies, their peculiarities, their dogs, etc.” But the right balance is important: Being overly familiar or too personal can also be unpleasant for participants.
“We’re interested in the data, but the wellbeing and respect of one human to another is more important.” –Paul McCann, University of Alberta
McCann says that the principal investigator at the Edmonton site, Oksana Suchowersky, makes sure that participants know they can also talk about health concerns when they come in for a study visit. “It’s not unusual for people to leave the research visit with a referral to physiotherapy or a prescription,” he says. “It’s a two-way street: You’re helping us with research, so we’ll help the best we can.” The team there also goes to fundraisers, walks and runs. “Not because we feel we have to, but because we want to,” he says. But people who see that the team supports HD outside of work may also be more willing to come in for research studies.
Stay in the loop
On a more practical level, logistical flexibility can also make a big difference. Because HD is a rare disease, study sites may be few and far between in nations with smaller populations. In those cases, participants may need to drive for hours to reach a study site. At CHUM in Montreal and at the Hereditary Neurological Disease Center in Kansas, Enroll-HD appointments are frequently held on the weekend. It’s easier for participants— although it may not be convenient for the medical staff.
“Accept that life happens and that there are more important things than a visit window,” says Paermentier. In their experience, people who drop out of the study usually do so for logistical reasons: they’ve moved, or can no longer take time off work, or the travel is too difficult, or their disease has advanced to the point where making a clinic visit is too arduous.
McCann has found that scheduling appointments far in advance is also a good idea. He calls a few months ahead of time, to make the trip as convenient as possible—then follows up in the weeks and days before the visit.
Keeping participants in the loop with regular communication is also a good way to retain interest, suggests Mestre. That might include updates about how the study is going, what the future holds, and updates about clinical trials.
The Christchurch team sends out a newsletter twice a year, which includes updates, personal stories and hopeful messages. “It comes down to good communication, and also good dynamics between the participants and the team, in the sense that the patient feels engaged,” adds Mestre.
Retention will become even more important in years to come as more and more people from Enroll-HD are offered the chance to be in a clinical trial of a new drug or other treatment. For ethical reasons, early-stage trials usually involve the smallest number of people that can still provide meaningful results. That’s done just in case there are unanticipated side effects. “Because it’s an experimental intervention, we don’t want to include more than are strictly necessary,” says Mestre. However, if many people drop out of a small study there won’t be enough data at the end to get a clear answer.
It’s also possible that in future researchers will begin to focus on some therapeutically important aspect of HD that is overlooked today, and having a decade’s worth of high- quality data already collected and organized could be crucial to such a discovery.
“Having long-term buy-in and commitment is important.”—James Moyer, Quintiles
Sometimes participants’ symptoms advance to the point that visits to the Enroll-HD site become too difficult. McCann mentioned one couple who drive more than nine hours for clinic visits. It would be too disruptive to make the trip this year, the husband told McCann. But he hadn’t yet told his wife, because he knew she’d be disappointed. She looks forward to the visit, he said.
That’s the kind of relationship that many sites have with some of their participants—a respectful partnership that leads to friendship. “We’re interested in the data, but the wellbeing and respect of one human to another is more important,” says McCann. “There has to be compassion, understanding, and give and take. HD is a demanding disease.”
This story was originally published in the Autumn 2016 issue of Enroll!