Relooking at refuseniks: Why did they say no?

Educate, make flexible study protocols

Often investigators can improve their clinical trial recruitment numbers by simply spending a little more time on education during the screening process, according to an expert.

Researchers at the National Institutes of Mental Health (NIMH) of the National Institutes of Health (NIH) in Bethesda, MD, have collected a decade's worth of subject recruitment, including screening interviews.

Potential participants were screened and carefully questioned when they proved to be eligible, yet many still declined to enroll in a clinical trial, says Julie Brintnall-Karabelas, MSW, LCSW-C, clinical research advocate of the human subjects protection unit of the Office of Clinical Director at NIMH.

Brintnall-Karabelas and co-researchers saw some potential in their data. What if they could identify trends in why people declined to participate and then use these to develop recommendations that might help improve future recruitment?

So they reviewed data, found several main reasons that people declined participation and came up with these general recommendations:

1. Increase awareness and education.

"The interdisciplinary team members who have initial contact with potential participants should have specialized training so they're equipped to answer any questions or concerns during the screening or recruitment process," Brintnall-Karabelas says.

"They should provide information to callers through verbal discussions or sending them health education brochures or fact sheets or links on the Internet," she adds. "This can alleviate people's concerns and answer their questions about research participation."

For example, there is a free, 25-page brochure available through NIMH, called "Participants' Guide to Mental Health Research." (It's publication 08-4379 and can be downloaded at www.nimh.nih.gov.)

"It is about the nuts and bolts of research," Brintnall-Karabelas says. "It answers basic questions about clinical research, including what rights I have, what is randomization, what is informed consent, and what is your alternative to research."

2. Build flexibility into study protocols.

Some potential study participants are skeptical of being involved in randomized, placebo-controlled trials because they don't want to be given a placebo.

So investigators who design protocols to have a second arm in which even the placebo cohort receives treatment might find that this increases enrollment, Brintnall-Karabelas says.

"A solution is to offer cross-over studies where there might be an arm of the study where you have a 50-50 chance of getting treatment or placebo," she explains. "But once you complete the first arm, then you can get actual treatment in the second arm."

This type of protocol design might be more appealing to some participants and draw in people who otherwise would decline to enroll.

"The more options offered to participants, the better," Brintnall-Karabelas says.

"There also are studies that allow participants to have an opportunity to make the choice to either be in an open label treatment study where they get the medication, participate in a placebo-controlled arm, or cognitive behavioral therapy," she adds.

"Flexibility is the key," she says. "People are more likely to participate in protocols that have options or have cross-overs."

Researchers should keep in mind that during the initial stages of protocol development, the public's perceptions are important. While a trial cannot be too flexible, it also cannot be too rigid, Brintnall-Karabelas says.

"Whenever possible, tweak studies to accommodate subjects," she adds. "Is it a good sample if you're leaving out a certain group because of extremely rigid inclusion/exclusion criteria?"

3. Address potential participants' concerns when possible.

There are actions both simple and more complex that clinical trial sites can take to reduce the burden of research involvement for participants.

For example, one solution to reducing the time-consuming paperwork portion of participants' study visits is to have them complete some of this initial paperwork and admissions forms before they have their first visit, Brintnall-Karabelas suggests.

They could complete some of this paperwork through encrypted e-mail, she says.

Also, it helps participants if a clinical trial site can offer after-work study visit hours.

"At NIMH, participants are very enthusiastic about coming to the clinical center after work at 5 o'clock or doing an MRI on Saturday morning," Brintnall-Karabelas says. "These appointments fill up right away."

Another solution might be to offer participants the option of an open MRI if they're claustrophobic and are reluctant to participate if a closed MRI is required, she adds.

And CR sites should consider participant compensation for studies, if they don't already do so.

"Remember that people are interested in studies that provide compensation," Brintnall-Karabelas says.

Lastly, CR sites could collect their own data on why people decline to participate, and these answers might provide clues that lead to solutions, she advises.

"I think the research community is really good at maintaining data regarding participants," she says. "But they also should maintain data on nonparticipants and those who withdraw from studies."