Silver Linings

A "failed" study ends well.
Photography courtesy of
Getty Images/Zwilling330

In 2013, study coordinator Busi Tshabalala was shocked to learn a major HIV clinical trial she’d worked on for three years had failed. The reason? Nearly three-quarters of the study’s more than 5,000 participants at research sites throughout Africa—including hers in Johannesburg, South Africa—had not consistently used the study products.

Tshabalala was in the room when around 60 study participants learned about what had happened. She recalls an overwhelming air of disappointment. Some cried. Some sat stone-faced. Others openly admitted they hadn’t stuck with it. They confessed they hadn’t been honest during the course of the study. Why? They didn’t want to disappoint the site staff.

The study, called VOICE, was launched in 2009 by the Microbicide Trials Network (MTN)—an international HIV clinical trials network based at Magee-Womens Research Institute. Microbicides are products, such as vaginal rings and films or rectal douches and gels, being designed and tested to help prevent the sexual transmission of HIV; millions of people throughout the world are living with the virus. 

VOICE had a noble goal: Offer women a method for HIV prevention—a daily pill or gel—that they could control, unlike, say, a condom. The trial’s failure meant such a product would not be realized for another eight years at least.

Yet the study led to a reckoning.

The way the trial organizers had set up the study and the assumptions they’d made had not gotten them where they wanted to be. They needed to engage deeply with these women—not just once or twice, but continuously.   

“As difficult as they were to accept, the VOICE results completely changed our approach,” says Sharon Hillier, a PhD, MTN principal investigator and professor and vice chair of obstetrics, gynecology and reproductive sciences at the University of Pittsburgh. “They compelled us to do things differently and understand the communities we were working with much better.” 

After VOICE, the data that came from MTN about acceptability, usability, attitudes and behaviors related to products for HIV prevention made a huge difference in the field, says Diane Rausch, a PhD, director of the Office of AIDS Research at the National Institutes of Health, a primary funder of the MTN. The National Institute of Allergy and Infectious Diseases and Eunice Kennedy Shriver National Institute of Child Health and Human Development also support MTN. 

VOICE organizers went back to the drawing board. They had interviewed participants during the study, but realized they needed to probe more to figure out what was going on. So they had research staff who hadn’t worked on VOICE ask the questions—away from the clinic. They pulled together focus groups. They conducted in-depth interviews. They also provided VOICE participants with blood tests that showed their actual patterns of product use during the trial, and asked why they thought their self-reports differed.  

What did they learn? Some women didn’t trust the products being tested. Some had heard rumors that the drugs were harmful or would make you infertile. Some believed that the products could actually give you HIV. Some didn’t like the way the pill tasted or the gel felt.  Others just couldn’t remember to use the product every day.

These lessons learned were applied to MTN’s subsequent trials—like REACH, which evaluated a vaginal ring and oral pill for HIV prevention among young women and adolescent girls ages 16 to 21. Giving participants a say not only before, but also during the study, helped encourage mutual respect among REACH site staff and study volunteers, says Kenneth Ngure, a PhD, MPH, cochair of the study and associate professor at the Jomo Kenyatta University of Agriculture and Technology near Nairobi, Kenya.  

REACH participants were clear about how they could be accommodated better: Youth-friendly clinic spaces. Shorter visits. Those specula used for pelvic exams? Too cold! Also, the girls wanted more privacy around their sexual health. (Surprise!) 

So, to preserve privacy, REACH limited the number of staff members present during clinic visits. To make pelvic exams more comfortable, clinicians started prewarming speculums. To make the clinics more welcoming, they hung posters and put out materials young people might enjoy reading.  

“We went back to look at our data collection instruments and cut some of the questions to make sure they were very focused, so we could reduce their time in the clinic,” says Ngure. 

“It was important that the participants knew they were partners in the process.”

Clinical psychologist Iván Balán, a PhD professor at Florida State University College of Medicine who has worked with the MTN since 2012, says: “There is a tendency to think that we can convince people to do something we want them to do, because we think, ‘If you just had all the information I have, you would feel just like me.’

“Our inclination is to give people more and more information, but it doesn’t work like that. It’s about making sure the information we are giving is linked to their goals.”

As MTN moved forward after VOICE, network researchers acknowledged that their products and approaches had to be much more user-centric.

They realized that the people they are trying to serve are experts about themselves. They know what they want and don’t want.  

Remember how women didn’t want to apply a product every day?

Pitt’s Lisa Rohan is developing and testing a long-acting vaginal film—that looks a bit like a Listerine breath strip. Rohan, a PhD, is principal investigator of MTN’s Laboratory Center and professor of pharmaceutical sciences in the School of Pharmacy. She also holds appointments with the Department of Obstetrics, Gynecology and Reproductive Sciences, the Clinical and Translational Science Institute and Magee-Womens Research Institute.

Women may have a means to protect themselves very soon.

The MTN has contributed to the first biomedical HIV prevention method developed specifically for women that’s under regulatory review—it’s a vaginal ring that the user inserts monthly. The ring, which cuts the likelihood of acquiring HIV in half, was recommended by the World Health Organization in 2021 and has been approved in several African countries. 

Adapted from "A Look Back, MTN Network," May 2021, with permission