TB Trials: Secrets to Success
words by maryann brinley /
photograph by pete byron
onita Mangura’s first clinical trial in 1983 was a pharmacokinetic drug investigation for asthma that brought new meaning to the word multitasking. It was a one-woman adventure. “I recruited patients, consented them, admitted them to the hospital, sat with them to allay their fears or discomfort, checked that their meal trays didn’t include anything we had prohibited and so on and so forth.” Because it was a nocturnal study, she stayed overnight for several weeks at the hospital to draw blood samples every two hours, centrifuge and transport the samples to the lab as well as perform periodic bedside lung spirometry. Months later, an admissions clerk told her that after the first phase of this trial was completed and a similar extension study begun, they needed three to four people to do what she did.
Since 1999, Mangura has been principal investigator for the New Jersey site of the Centers for Disease Control (CDC) Tuberculosis Clinical Trials Consortium which includes 23 U.S. and international academic institutions. Over the last 10 years, her group has participated in 10 United States Public Health Service (USPHS) studies and enrolled more than 486 patients. Two open protocol investigations now aim to shorten TB prevention and treatment from nine to three months and six to four months respectively, to assess new drugs in Phase 3 trials, and to promote international collaboration.
“What could be better than this,” says Mangura, who is affiliated with the NJMS-Global Tuberculosis Institute (GTBI). “Work that I enjoy. A topic that I have a passion for. Travel, which I love to do.”
In the 1980s, NIH-funded research on the pulmonary complications of HIV “fortuitously blended with the resurgence of tuberculosis in Essex County, New Jersey.” Lee B. Reichman, MD, MPH, her executive director at GTBI, also has a “vision and passion for tuberculosis that is contagious,” she explains. The GTBI research unit functions efficiently because of a “superb” staff including Cora Leus, RN, Eileen Napolitano, GTBI deputy director, Alfred Lardizabal, MD, GTBI assistant director of research, Reynard McDonald, MD, GTBI medical director, Lillian Pirog, RN, and a cadre of nursing and outreach staff at the Waymon C. Lattimore Practice, which provides outpatient services. This clinic was evaluated in 2006 by Quintiles, commissioned by the international organization Global Alliance for TB Drug Development, and determined to be “implementation ready” for any international clinical trial on tuberculosis. In 2008, she says, “We were one of only five U.S. sites with such a distinction.”
The fact that every staff member is certified to conduct human subjects research has helped earn the unit’s credibility with patients. And, whether or not someone even chooses to join a trial, their TB care is the same. “The aim is to flawlessly integrate research participants with non-participants. Everyone is treated equally,” she explains.
Two secrets to their successful retention of patients are: an incentive they described in the International Journal of Tuberculosis and Lung Diseases in 1997 and their nurse case management with directly observed therapy. TB trials can be tough for patients because the drugs are potentially debilitating and toxic, and people sometimes have no symptoms convincing enough to make them want to continue months-long therapy. Those at the highest risk for active TB are HIV-infected or injection drug-users. So “adherence to tuberculosis therapy is a universal problem.” Using money, ride vouchers and meals to bring people in for therapy had been tried. However, Mangura and her team noticed that many TB patients requested Sustacal®, a liquid nutritional supplement, at clinic visits. Evidently, HIV-infected patients were aware of the high vitamin and protein value of this beverage so Mangura started making cases available to participants with defined nutritional needs based on their body weights. Mangura is careful to point out that “prescriptions for Sustacal® were not suggested, encouraged or offered freely by the study staff.” Because of its popularity, however, adherence among participants who took advantage of it, improved.
The GTBI “pioneered the use of this incentive now commonly used across the country for patient retention in TB trials. We have always maintained above average retention, more than 90 percent, among our subjects. In the eighties and nineties, there was a pervasive fear of ‘not wanting to become a guinea pig’ for medical research. I rarely hear that comment nowadays,” Mangura says. “We’ve had to earn our credibility in the community for a caring service as well as a clinical research site. And we have!”