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When Eiger Biopharmaceuticals began looking for patients to enroll in a clinical trial for lymphedema drug Ubenimex, Joanne Quan, M.D., chief medical officer of the Palo Alto, California-based company, kept hitting a wall. The usual route — outreach via physicians and therapists — netted “very few” participants, she recalls. Given the specifics of the condition — it has typically been managed by therapists using manual techniques rather than drugs, and outside traditional hospital settings to boot — enrolling the trial seemed a herculean task.
So Eiger decided to try something new. It started working with Paul Ivsin, now managing director of clinical trial strategy and patient recruitment at the Patient Experience Project.
The playbook they devised included everything from Google Ad Words and geographically targeted Facebook ads to a partnership with LE&RN, the Lymphatic Education and Research Network, on a Livestream symposium. “We used it to tell patients what a clinical trial is and to explain informed consent and what it means to be randomized,” Quan says. The tactics worked: In addition to generating valuable feedback from potential subjects, the company was able to build a database of interested parties.
While such tweaks might sound routine for marketing projects in other verticals, they represent a breakthrough in the world of clinical-trial recruitment, which still relies heavily on physician referrals, transit ads, and even newspaper classifieds. Quan says Eiger’s success with the new approach means the company will likely be more willing to further fine-tune its awareness-generation tactics.
“Everyone is online looking for health information these days,” she says. “So this becomes another communications tool.”
[On January 16, Eiger announced that it had stopped development of Ubeminex in certain indications after the drug failed in a mid-stage study.]
At the same time, Eiger and other pharmaceutical companies are fighting an increasingly uphill battle. While there’s a broad general awareness of clinical trials — Research!America, a nonprofit advocacy group, recently reported that 80% of Americans know what clinical trials are — only 18% said they or someone in their family have participated in one. And while 74% of respondents said they would participate in a trial if asked, most say lack of information and awareness are the major stumbling blocks.
“As an industry, we do a terrible job telling our story,” Ivsin explains. “You’ve got fantastic people conducting trials, with serious dedication. Standards of proof are so high that 90% of these compounds fail. Yet we never tell people about that.”
To restate the obvious, clinical trials are essential to the industry and, as drug development costs continue to rise, they are more important to its growth than ever before. “We’ve never had this many trials, and there is more complexity,” says Fabio Gratton, cofounder and CEO of CureClick. “Many trials are so nuanced with precision medicine — participants may need to have certain biomarkers or they must have been diagnosed within a certain time frame.”
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SMALLER NEEDLES, BIGGER HAYSTACKS
And while the industry has been kvetching about recruitment headaches for decades, according to inVentiv Health head of global clinical trial engagement Marie Emms, “Today’s protocols sometimes dive so deep looking for a very specific person that it seems like those patients don’t even exist.”
What compounds the frustration, Gratton adds, is the sudden glut of tools to navigate the complexities of trial recruitment. “No one has ever had this much data. We’ve got registries, databases, and machine learning,” he explains. “[But] we are much worse for it.” Despite all the additional options, Gratton estimates that “physicians probably still generate between 80% and 90% of referrals [for trials].”
Absent a doctor’s recommendation, even motivated would-be participants tend to hit one speed bump after the next, says Joseph Kim, senior adviser, clinical innovation at Eli Lilly. After finding their way to places such as ClinicalTrials.gov, he explains, interested individuals “try and contact those running the trial, then play phone tag. And when they do connect, they begin to understand the many hoops they’ll have to jump through — all the time they’d need to take off, how far they’d have to drive.” Gratton agrees, adding, “There’s nothing like a Yelp or an Amazon to help people evaluate trials.”
Then there’s the underlying factor that can suck the trial-sleuthing energy out of even the most determined patients: “No one really wants to be in a clinical trial,” Gratton says. Given a choice, people would prefer not to be sick at all.
See also: Memo to New CEOs: Prioritize Diversity
The struggle to recruit a more diverse pool of participants also slows recruitment efforts. Between the infamous Tuskegee Syphilis Experiment of 1932 and the unauthorized culturing of cells from Henrietta Lacks in 1951, many experts say African-Americans are wary — justifiably — of medical researchers.
Ivsin disagrees, pointing out research conducted by the Center for Information and Study on Clinical Research Participation (CISCRP) reveals African-Americans and Hispanics are less likely to drop out of clinical trials and more likely to say that participation resulted in getting better care. Similarly, a Research!America study notes African-Americans tend to be somewhat more altruistic about participation, with 61% saying the opportunity to help improve health for others is very important to them, compared to 56% of Hispanics and 50% of non-Hispanic whites.
African-Americans are also more likely to believe that the dissemination of information about clinical trials should be part of the communication around routine care. “We need to stop blaming Tuskegee and start working to engage people,” Ivsin explains. “They don’t participate for the same reason everyone doesn’t participate. It’s because we don’t ask them.”
Patients want to help — and don’t mind the inconvenience, even if they wind up as part of the placebo cohort. A study published in BMC Cancer, which looked at a group of patients invited to participate in clinical trials for cancer drugs, found that 93% consented and 89% said they had no regrets. And in its latest report, the CISCRP found that 95% would recommend participation to a friend or family member.
“We know participants are rooting for us,” Kim says. “They want us to find better medicines.”
He adds that companies can help their recruitment efforts by reversing the way they think about informed consent. “You do need to inform people before getting their consent, and that’s a fundamental tenet we will never break. But the reverse isn’t true,” he explains. “I don’t have to get your consent to a trial in order to inform you.”
For example, Lilly’s Trial Guide walks potential participants through the basics. “It gives people a chance to think about things such as, ‘Oh, there might be a blood draw and I hate needles.’ That way, we don’t waste their time. They like to be respected,” Kim adds.
For Gratton, the a-ha moment came when he convened a group of influential patient advocates. “We asked what they wanted from pharma companies. What they asked for was info about clinical trials,” he says. “We should have known they’d ask for something of substance, and they did. They get it. They say things such as, ‘Pharma is saving our lives.’”
That’s not to say the relationship between these groups and pharma companies can’t be adversarial, especially around issues including pricing. “But in the R&D period, when drug companies are spending money on research and not making it by selling the medications, patients say, ‘The drug company is on our side. We consider them the good guys,’” Gratton continues.
That said, Emms notes that motivation levels vary a great deal. “A patient with a severe cancer diagnosis who has exhausted all his or her treatment options is going to be more motivated than someone with chronic low-back pain,” she says.
For better or worse, nobody expects the situation to change quickly — and it doesn’t help that the industry is simultaneously grappling with the issue of compensation. Agencies often aren’t paid until they find the right trial recruits. “Right now, it’s set up like it is for bounty hunters,” says Gratton. “It’s like, ‘Find me a needle in a haystack, and then I’ll pay you.’”
But the biggest hurdle is the easiest one to understand: Potential participants are suffering. “One of my most difficult assignments involved recruiting people in the early stages of Alzheimer’s, when they might still be telling themselves they’re just getting a little forgetful as they age,” Emms recalls. She adds neonatal studies are among the most wrenching: “Parents have to make quick decisions and put such trust in the study team.”
TIPS FOR IMPROVING AWARENESS OF OPPORTUNITIES FOR RESEARCH PARTICIPATION
SHAKE OFF GEOGRAPHICAL LIMITS
Limiting trials to people who live within shouting distance of trial sites is as antiquated as physically entering a bank. “People don’t do that anymore,” Kim says. “We need to create trials where people are.” That may mean using more community clinics or even home visits. “Can we create more trials that rely on wearables, or use metrics that might even be collected at retail clinics?” Kim asks. Some companies, such as Science 37, are already working on ways to develop “site-less” clinical trials.
RETHINK SOCIAL MEDIA
“Ten years ago, we were all looking at Facebook,” says Emms. “Now, many millennials don’t even use it, so we’re advertising through Spotify and Pandora.” Kim points to pioneers such as Doctor Miami, a plastic surgeon who uses Snapchat to show potential patients what recovery really looks like, as setting new standards for transparency. However, Emms points out that the use of social media to generate awareness poses risks, because sharing during a trial could compromise results. “We are seeing more sponsors put social media restrictions in their consent forms,” she says.
TURN PARTICIPANTS INTO ADVOCATES
Even though the majority of participants say they are interested in the final results of the trial, 51% say they never received them. But while companies must steer clear of seeming to promote a medication before it has received approval, Kim notes that “there’s irony in that we sometimes say more to investors about a trial’s potential than we do to participants. And it’s not like we want to keep them in the dark about what we’ve done. Once they have this positive experience, how do we invite them to be part of the team?”
CONSIDER INDUSTRYWIDE EFFORTS
The Coalition for Clinical Trial Awareness, an industry group, has called for a public-service campaign aimed at increasing awareness. It’s suggested that such a program could be modeled in part on the Donate Life effort of the 1990s. Before it started, just 28% of Americans registered as organ donors; today, that figure is close to 50%. “We are moving the needle,” says Gratton. “But we have lots of needles to move.”