Clinical trials have always been a centerpiece of how medical research moves forward to establish that new treatments are safe and effective. This year, as COVID-19 spread from country to country, clinical trials for treatments and vaccines for the new coronavirus drew massive public attention. Trials were launched in record time throughout the world, including more than a dozen at Penn Medicine investigating COVID-19 testing, treatment, and vaccine development.
“The number of cases was increasing and patients were critically ill,” said William R. Short, MD, of Infectious Diseases in the Perelman School of Medicine, who is the principal investigator (PI) on a trial investigating the anti-viral medication remdesivir, sponsored by the National Institutes of Health (NIH). “The foot was to the pedal to get a treatment, something to offer patients.”
And behind every trial, there was a huge team effort that is often largely unseen. Clinical trials in the news often focus on the study’s PI — the research physician who leads the trial. But the PI is only the tip of the iceberg. Behind the scenes of any clinical study is a team of dedicated employees who keep the operations running smoothly. At Penn Medicine, there are approximately 1,000 clinical research staff, including clinical trial regulatory staff, clinical research assistant and nurses, and clinical research project managers and directors.
And then there are research coordinators. They oversee everything that’s required to keep a clinical trial adhering to strict regulations. They make sure the PI gets the daily notes done. They make sure patients get the correct medication at the right dosage — and all the necessary labs drawn — at the right times. Coordinators even make sure that tubes are readily available to collect the samples. No detail is too small.
Their work has always been essential to the successful outcome of studies, but the COVID pandemic brought new urgency to these responsibilities. In response to the needs of the crisis, clinical research staff from across Penn Medicine stepped up in new ways to coordinate COVID-related clinical trials, learned new ways of doing their jobs, and have proven to be key unsung heroes of the coronavirus response.
Eileen Donaghy, clinical research manager in Infectious Diseases, experienced this urgency to get trials up and running firsthand. She herself was tasked with pulling together four COVID trials, including the NIH’s trial of remdesivir. The drug has also been studied for hepatitis C and Ebola, as well as SARS and MERS, which are caused by coronaviruses.
Knowing she did not have enough staff from her own department to run four trials, Donaghy reached out to the Office of Clinical Research and the Department of Medicine for help. And the response, she said, was “heartwarming.” Research coordinators — as well as other members of research teams — came forward from across disciplines: Dermatology, Women’s Health, Cancer, Rheumatology, to name a few.
“These volunteers don’t usually work in infectious disease trials at all, but opted into contributing for this urgent need despite the personal risks involved,” said Amanda Baer, director of Clinical Operations for the Department of Medicine. “They stepped up during a time of high uncertainty about how things would roll out.”
And then the real work began.
With the study teams in place, the enrollment process could start. To find study subjects, a research coordinator’s job includes understanding the study protocol and pre-screening patients to see who is eligible. This long, involved process normally takes months to complete. And for most trials, coordinators typically enroll 4-5 patients a month. But the COVID crisis required a rapid response. For the NIH trial of remdesivir, they enrolled 20 patients within two weeks.
Once the trial was up and running, coordinators needed to retrieve all pertinent study data from the PennChart electronic health record every day and transcribe it onto paper charts. But for coordinators volunteering for COVID trials outside their usual discipline, navigating the records system for inpatients proved challenging, said research coordinator Emily Stumm of Infectious Diseases. Unlike subjects in outpatient trials that she usually works on, COVID patients were extremely ill and their medical records were filled “with many different provider notes, imaging, medications and labs, and it wasn’t all in one place,” she said. “It was a learning experience.”
And following the day-to-day progress of these critically ill patients proved to be an emotional experience as well. “Many of these coordinators don’t see patients dying in a study,” Donaghy said. “This speaks to the stress they’re under.”
Providing coverage seven days a week was yet another hurdle. Outpatient trials typically run during normal business hours. A work schedule for the NIH remdesivir trial was quickly established but even so, research coordinators and other members of the team often worked long shifts and many days in a week. Donaghy herself worked an entire month with no days off.
The trials were definitely about team work. Research coordinators often helped key in the enormous amount of data generated from the medical records. And although a dedicated “runner” ferried all lab work and specimens from the study subjects at HUP and PPMC across campus to Penn’s Johnson Lab for processing, research coordinators — and Donaghy herself — sometimes took on the task as well.
Indeed, when Jack Allard, a critically ill 25-year-old patient, was flown to PPMC because his family hoped he could take part in the NIH remdesivir trial, research coordinator Rupa Chowdary literally ran his SARS-CoV-2 screening test (to determine eligibility) to the HUP lab to ensure that it was within 72 hours of receiving the first dose (of either remdesivir or placebo). “I took all shortcuts to HUP!” she said, laughing. “We all wanted him in the study.” Allard went on to make a full recovery and was discharged in mid-April.
Not all of the study testing took place in the hospitals’ ICUs. Each of the study patients needed to remain in the study for 29 days. Patients discharged before that had to come back to complete the study. The safest place to perform the final swab turned out to be the basement of the garage in the Perelman Center, which was closed at the time. With patients remaining in their car, Donaghy and research coordinators, fully donned in PPE head to toe, took swabs through the car window and had them come to a nearby space with screens on wheels and where blood work could be drawn.
“When I called asking these patients to come in, we were establishing a relationship that we didn’t have before,” Donaghy said. “We only knew these patients as numbers on a chart.
“We told them ‘We followed your progress every day although we never met — we knew every detail,’” she continued.
The first phase of the NIH remdesivir trial showed that the drug showed some benefit to patients with the disease. Phase II of the trial, in which remdesivir will be paired with another drug (baricitinib), was recently launched… and the whole process has started again. Two other remdesivir studies at Penn — sponsored by Gilead Biopharmaceuticals which makes the drug — are in Phase III of investigating the drug's impact on inpatients with moderate COVID cases and those with severe COVD-19.
But Stumm and others who will be part of the new teams are ready. Although the hours were long and the work hard, Strumm saw her role on the first phase of the remdesivir trial as rewarding. “When I saw in the news that remdesivir was effective, it was a positive reinforcement for all we’ve done,” she said. “We’re working on something important that could impact the world.”