Good retention starts with good recruitment
Experts discuss best strategies
Clinical trial sites have first-hand knowledge of patient recruitment problems, but the statistics are startling, just the same: Four out of five studies don’t meet their recruitment time lines; delays can cost sponsors hundreds of thousands of dollars in just one clinical trial; and nearly half of study delays, which mostly exceed six months, are due to subject recruitment problems.1,2
A United Kingdom study found that 30% of UK sites fail to recruit even one patient, and other studies have shown that patient recruitment around the world costs $5.9 billion annually, while only one in 20 recruited patients provides meaningful results.3,4
The problem likely will worsen as a rash of visible problems with popular drugs, such as rofecoxib (Vioxx), could lead to more post-marketing clinical trials, in which sites continue to compete for a patient base that is unlikely to expand enough to meet the increased demand, experts say.
"Trials end up being delayed because they can’t enroll enough [subjects], and the problem only increases when there are new compounds on the market. Now it’s worse with situations like we have with the Cox-2 inhibitors and with more safety studies being required," says Tom Sturgis, president of Integrated Clinical Trial Services of Cary, NC. Integrated Clinical Trial Services helps sponsors and clinical research organizations with patient recruitment.
Thomson CenterWatch of Boston has data showing that in a typical study one in four enrolled subjects will drop out, notes Beth D. Harper, MBA, senior vice president of global operations for D. Anderson & Co. of Dallas. D. Anderson is a comprehensive patient recruitment and retention provider.
Recruiting from existing hospital and clinic databases also is complicated by state and federal regulations, including the new privacy concerns raised by HIPAA, says Stephen W. Bernstein, JD, a partner with McDermott Will & Emery of Boston. Bernstein is the co-chair of the HIPAA Practice Group at the law firm, and he co-chairs the firm’s health ventures group.
The old-fashioned way of finding these patients works very slowly, as it takes physicians finding patients on a one-by-one basis, Bernstein notes. New methods make it possible to search through vast amounts of patient databases to look for cohort types that might be appropriate for a particular study, he explains. However, these types of searches sometimes result in confusion among researchers and clinical trial professionals because of interpretations of HIPAA and Common Rule requirements, Bernstein says.
"Initially it was thought that HIPAA implied clinicians had to have patient consent to cull through records looking for patients who might be candidates," Bernstein says.
Now with some HIPAA history available, including a series of clarifications about HIPAA, it appears that this type of clinical trial subject search is allowed, he says.
This is why pharmaceutical companies, clinical research organizations, and medical research institutions increasingly are focusing on ways to improve both clinical trial recruitment and retention.
Here are some suggestions for how clinical trial sites could improve subject recruitment:
- Target potential patient populations with proven methodology.
"Recruitment is very dependent on the therapeutic area of the protocol," Sturgis explains. "You have to factor in specifics with the protocol and start with the demographics of the eligible subjects."
A basic formula for finding subjects involves taking the information gleaned from basic research on the disease, the prevalence of the disease, and its incidence level and matching this information against the inclusion/exclusion criteria of the protocol, Sturgis explains.
Then site recruiters have a good idea of their target audience and will have to develop a strategy to best deliver messages to those people, he adds.
For instance, with Alzheimer’s disease, patients often aren’t able to recognize and understand a request for research participation, so the audience to whom recruitment messages are delivered should be their caregivers, Sturgis says.
"You have to reach the caregiver constellation, and that might be more than one person, including a member of the clergy, patient advocacy groups, and others," he says. "Use as many tools as you can to reach as wide of an audience as you can."
Since recruitment budgets are limited, the goal is to quickly educate potential subjects about the clinical research and the specific trial’s availability, Sturgis says.
"Deliver a call to action and have it enticing enough to create some interest, but it can’t be coercive in any way," Sturgis notes.
If a clinical trial site is using direct consumer advertising through radio, television, newspapers, or the Internet, then there will have to be a telephone screening process during which results are quickly analyzed to make certain the marketing efforts are reaching the appropriate population, Sturgis says.
- Refine recruitment screening to reflect experience.
By making recruiting and pretrial screening a continuous process, it’s possible to improve recruitment marketing and save time and money, Sturgis says.
For example, suppose there is a diabetes trial in which the inclusion/exclusion criteria list a range of body mass index levels that are acceptable. "You can use that in your screening process by asking a person’s height and weight," Sturgis says. But as the screening continues, it might be discovered that people typically are underreporting their weight. So if the screeners are excluding people on the borderline of the low weight on the range identified in the inclusion/exclusion criteria, then they may be missing people who really are within the acceptable range, Sturgis explains.
Following up the screening process can be time-consuming, but it’s worth the effort, Sturgis says.
"You want as much feedback from sites as possible," he says. "Sponsors always will have an enrollment log, but if it’s planned really well, they’ll use a screening log that categorizes everyone who has been screened and why they were excluded."
Sites that recognize the screening log as a valuable tool are able to make it work for them and improve their enrollment efficiency in the process, he says.
1. Anderson DL. A Guide to Patient Recruitment. Boston: CenterWatch/Thomson Healthcare; 2001.
2. Patient Recruitment: The Growing Challenge for Pharmaceutical Companies. IBM Global Industries. www.ibm.com. 2002.
3. Final Report. Pharmaceutical Industry Competitiveness Task Force. www.abpi.org.uk. 2001.
4. Fraser HE, Drayton S, Wang AE. Delay no more: Improve patient recruitment and reduce time to market in the pharmaceutical industry. IBM Institute for Business Value Study. 2003.