More than 37 million people around the world are blind and over one million of these live in the United States. In fact, eye disorders are responsible for 3.1 percent of disease worldwide according to the 2003 World Health Report, composed by the World Health Organization.
National and international efforts to improve these statistics have generated biomedical research advances, experimental new treatments and even potential cures for many eye disorders. But the only way to determine whether these new treatments are safe and effective and offer an improvement over current therapies is to test them on large numbers of patients in carefully designed and controlled clinical trials.
Across all of medicine thousands of clinical trials are conducted each year. The NEI alone supports clinical trials in approximately 250 medical centers, hospitals, universities and doctors’ offices in the United States. But finding, screening and enrolling patients who fit the eligibility criteria for a trial can present a challenge even to the most experienced researcher.
Although an abundance of literature addresses other aspects of research design, practical advice about recruiting patients for clinical trials is somewhat limited. Successful recruiting strategies are sometimes discovered by trial and error.
“It’s really hard work. We’ve been very successful, but does that mean we haven’t encountered any problems? You have to remain dedicated and motivated. If one recruitment strategy doesn’t work, you have to regroup and say it didn’t work and decide what to do next,” said Karla Zadnik, OD, PhD, professor of optometry at Ohio State University.
Obstacles to Recruitment
Why should recruiting participants for a study be difficult? After all, taking part in a clinical trial offers patients a number of benefits that they might not have access to otherwise: a treatment that may improve their vision or prevent an eye disease or disorder; intensive, quality medical care from clinical specialists; the satisfaction of contributing to a growing body of information that may help other people with vision loss in the future.
The spirit is willing. Some say it’s not a big problem. “I haven’t had substantial numbers of patients decline to enter a clinical trial,” noted Walter J. Stark, MD, professor of ophthalmology and director of the Stark-Mosher Center for Cataract and Corneal Diseases at the Wilmer Eye Institute.
But, he added, “Some may not be able to fulfill the follow-up requirements. Some may not want to participate because the procedures may be uncomfortable. Some studies require taking photographs during a visit, and patients may not want to be exposed to the bright camera flash. Some don’t want the discomfort of the dye injection used for angiography. But it’s not because they’re skeptical of doctors or concerned that their doctors might involve them in a study they shouldn’t participate in. If patients understand that they have a 50-50 chance of receiving the current therapy or a new therapy that might be an improvement, patients will usually participate.”
Myth and misperception. Nonetheless, a 2005 Harris Interactive online survey of 2,261 adults in the United States found that the three greatest perceived risks of participating in clinical research are possible side effects (47 percent), health risks (32 percent) and unproved therapy (9 percent).¹
Another Harris Interactive online survey conducted in 2002 revealed that few adults are convinced that clinical trial participants receive high-quality care, receive honest and accurate information and aren’t treated like guinea pigs.²
Both subtle and overt messages, particularly those propagated by mainstream media, may have some effect on these uncertainties. Negative publicity, such as Time’s April 22, 2002, cover that pictured a woman in a cage with the caption “How Medical Testing Has Turned Millions of Us Into Human Guinea Pigs,” may have caused some readers to question the motivations of scientific research. Further, said Dr. Zadnik, “When a patient dies during a gene therapy trial and it’s highly publicized, it downgrades that type of research in terms of the willingness of people to participate in biomedical research.”
How to Improve Recruitment
One proposed solution for helping patients overcome concerns about participating in clinical trials is the appointment of “research subject advocates who would simply sit down with the potential research subject and discuss in plain words what the study is about—the risks, the gains, and answer questions—what they’re getting themselves into,” explained Dr. Zadnik.
An article in IRB Ethics & Human Research³ explored this idea and similarly noted that “a patient advocate is responsible for ensuring that prospective clinical trial enrollees understand the risks and benefits of the research study, and must tell prospective research subjects whether or not it is in their best interest to enroll.” The notion of a patient advocate has a number of different understandings in the medical community, however, so it may be a challenge to create commonly understood responsibilities for such a position.
Excluded by design? In some cases, the inability to recruit participants may inadvertently be a problem with study design.
For example, Michael X. Repka, MD, professor of both ophthalmology and pediatrics at Johns Hopkins University, related his experience with a study conducted during the late 1980s: “It was a small clinical trial to look at how best to manage the surgical dosing for children with acquired crossing of the eyes. The project was conducted in just a few practices and had difficulty recruiting children. We found a result, but it was not dramatic. The eligibility criteria were written so stringently that many children were not eligible and the generalizability of the results was limited. One of the important things is that clinical trials have to be generalizable to be useful and to be eventually applied to clinical practice.”
Bring the study to the studied. The 1997 creation of the Pediatric Eye Disease Investigator Group (PEDIG), a network that has grown to more than 250 clinicians at about 100 sites across the country and is funded and supported by the NEI, addressed the problem of patient recruitment in a new way.
“The idea,” explained Dr. Repka, PEDIG chairman, “was that by developing a network that has many community-based providers and more open eligibility criteria, more patients will be able to participate. The network will have more doctors who have access to these patients, and the patients will be similar to patients in the community. The advantage of this size network is that each doctor can enroll just a few patients to complete the study. If you only have a few sites, every site would have to enroll a lot of patients.” Seventeen PEDIG studies have been completed or are under way.
Methods of reaching potential candidates for participation in a study are quite varied and depend on the type of clinical trial being conducted. “In general you think about where the people you’re looking for are most likely to be. Go there to recruit them—that’s the most successful,” explained Dr. Zadnik.
For example, Dr. Zadnik is investigating the correction of astigmatism in Native American children. “A member of the tribe is on the steering committee and has ways of communicating directly with tribal members on and off the reservation. The trick is figuring out where [potential recruits] are so the message gets to them. Another thing we’ve learned is that if you can somehow take your examinations to the community, you do better than when you expect mom and dad to bring the kids to you.”
Trial by Click and Search
The Internet, a relatively new source of patient recruitment, has an ever-increasing role in informing patients about clinical trials that are currently recruiting patients. ( See “The WWW Solution” below for suggested sites.)
Before the Internet became popular, most patients were recruited for clinical trials directly by their physicians and occasionally through mass media advertising.
“Nowadays, people get a diagnosis, get online and read about it. Sometimes they happen on studies that they may have never learned about before the Internet,” said Dr. Zadnik.
1 New Survey Shows Public Perception of Opportunity to Participate in Clinical Trials Has Decreased Slightly From Last Year (Harris Interactive Poll; June 27, 2005: www.harrisinteractive.com/news/allnewsbydate.asp?NewsID=941).
2 There Are Many Reasons Why People Are Reluctant to Participate in Clinical Trials (Harris Interactive Poll; March 26, 2002: www.harrisinteractive.com/news/allnewsbydate.asp?NewsID=439).
3 Morreim, E. H. IRB Ethics & Human Research 2004;26(6):1–8.
Drs. Repka, Stark and Zadnik have no related financial interests.