CR work leads to greater understanding of barriers
CR work leads to greater understanding of barriers
Microbicide trial site was canceled unexpectedly
Family Health International (FHI) of Research Triangle Park, NC, conducts many research trials overseas since the nonprofit organization focuses on improving reproductive health and preventing the spread of HIV and other sexually transmitted diseases worldwide.
However, even with all of FHI's experience and the overlapping experience of FHI investigators involved with microbicide trials as a part of the Alliance for Microbicide Development, few could have anticipated some of the problems that arose during a recent microbicide clinical trial, says Leigh Peterson, PhD, a scientist and project leader for the West Africa Oral Tenofovir Study at FHI.
FHI scientists began to investigate an HIV drug called tenofovir to see if this drug used as a prophylaxis could prevent HIV infection in women. The study enrolled 936 HIV-negative women in Ghana, Cameroon, and Nigeria, Peterson says.
Several problems arose and the trial ended without clear outcomes, as a result, Peterson says.
For example, the Cameroon site's work was discontinued due to what could best be characterized as political problems.
"In Cameroon, there were some concerns by the Ministry of Health, regarding post-product follow-up of seroconverters," Peterson says. "They wanted to look into that issue, and while they did, they decided not to allow the product use to continue."
Several months passed, and the nation's Ministry of Health still withheld permission for investigators to use the product, Peterson adds.
"After a number of months, it was not feasible for us to start the trial, and so we had to close it," she explains. "We never did find out why they wouldn't let us give it out."
When Cameroon's Ministry of Health sent investigators a list of questions, they answered all of them in a timely manner, but they still were not permitted to distribute the product to trial volunteers, Peterson notes.
This problem occurred despite the clinical trial staff's and the investigators' earlier efforts in obtaining IRB and Ministry of Health approval, she says.
"That was a tough one," Peterson says. "You start a study and get all of your approvals, and then there's a political change with a new prime minister or minister of health, and if they don't completely understand what's going on, then these things can happen."
Problems also arose with the trial's other sites because of an unexpectedly high pregnancy rate among study participants, Peterson says.
Tenofovir's health risks to pregnant women are largely unknown, so it had been decided that any woman participant who becomes pregnant while using the drug would have to discontinue use of the product, Peterson says.
"So we asked the women if they had any intention of becoming pregnant in the next 12 months, and they were not included in the study if they did intend to get pregnant," Peterson says.
Even with informed consent and lengthy explanations to women participants about the risks of becoming pregnant during the trial, about 50 percent of the women participants became pregnant, Peterson says.
"So that was a lot higher than we thought," she says. "We thought maybe 20 percent would get pregnant."
As a result, there was limited product use, Peterson says.
"The pregnant women were never dropped from the study, but they just did not receive product while they were pregnant," Peterson says.
A number of the women had abortions, so as soon as they had a negative pregnancy test, they were able to resume use of the product, she adds.
"The two major reasons the participants already enrolled in the study did not use the product was because they were either pregnant, or the woman had missed a visit and could not pick up a bottle of pills," Peterson says.
The goal was to have the product used at least 80 percent of the time and a pregnancy rate of around 10 percent, she notes.
Instead, the product was probably used no more than 70 percent of the time, due to the high pregnancy rate and other factors, Peterson says.
"For future studies we're going to provide contraceptives to the participants who want it, and the study staff will have contraception available at enrollment, so they can start then," Peterson says.
Investigators had anticipated many of the problems and barriers that exist in a resource poor international setting, Peterson says.
"We were prepared for translation problems, and we knew we needed to have witnesses or participant advocates available during the informed consent process in case participants couldn't read," Peterson explains. "And I feel like we did a good job of explaining these difficult concepts to participants."
Because of the nature of FHI's work, there is a very detailed and long informed consent process in which every word is explained to the participant in the presence of a witness, Peterson adds.
Perhaps one way investigators could have improved informed consent would be to ask participants questions at every follow-up visit and at each consent process during the screening and enrollment to make sure they comprehend the issues, Peterson says.
"Right now we would ask questions verbally and not document the answers," Peterson says. "But I think we might begin to use a much more structured questionnaire or something."
Some clinical trial staff thought participants didn't comprehend the issues as well as they had thought, so it would be helpful to have better documentation of the perceived comprehension, Peterson says.
Another change investigators might make is to enroll twice as many participants, expecting that unanticipated obstacles could reduce the possibility of a clear answer to the study question, she adds.
Family Health International (FHI) of Research Triangle Park, NC, conducts many research trials overseas since the nonprofit organization focuses on improving reproductive health and preventing the spread of HIV and other sexually transmitted diseases worldwide.Subscribe Now for Access
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