No champion race car driver can win without a dedicated pit crew. The same is true in medical research. Thanks to their “pit crew” Mayo Clinic researchers were able to repurpose an experimental therapy, called lenzilumab, for patients with COVID-19 pneumonia, and from there into a phase three clinical trial — all in about one year.
"I think we’ve accomplished in this year what normally would take seven years," says Saad Kenderian, M.B., Ch.B., a Mayo Clinic cancer researcher.
Claudia Lucchinetti, M.D., director of Mayo Clinic’s Center for Clinical and Translational Science (CCaTS) says the way the science, people, and resources came together was extraordinary and that “it wouldn’t have happened just about anywhere else but at Mayo Clinic.”
Jenny Weis, research administrator for CCaTS, agrees. "We assembled the ‘A-Team. We took what we were already experts at and we held hands and we sprinted.”
Stepping on the Gas for COVID-19 and Lenzilumab
At the beginning of the pandemic, experimental therapies were the only options available to help patients. To turn those therapies into standard care required clinical and translational research. Research leaders turned to experts in the Mayo Clinic Center for Clinical and Translational Science to help streamline the institution’s COVID-19 research strategy.
“We knew that in order to do our best work and to have the greatest impact for patients, we needed a union of forces. We had to organize ourselves, prioritize and move together as one," says Andrew Badley, M.D., chair of the Mayo Clinic SARS-CoV-2 COVID-19 Research Task Force, a group charged with oversight of all COVID-19-related research activities.
This multidisciplinary group aligns research projects and resources across the institution. They rigorously review every COVID-19 research proposal, approving only those posing the best questions or with the highest likelihood of helping patients. When the task force sees a COVID-19 research idea with potential, they give it the green light and a dedicated team of experts from CCaTS to help activate the study and keep it moving forward.
To get the lenzilumab research efforts up and running, the CCaTS crew focused on:
Rapid human research reviews: Before it can recruit patients, a research study is reviewed by an Institutional Review Board (IRB). Made up of clinical research professionals, the board ensures the rights, privacy and welfare of human participants are protected, and government regulations are followed. At Mayo Clinic, this review normally requires 20-25 days; however, the IRB’s pace accelerated for COVID-19 research with a goal to complete reviews within 72 hours of submission.
R. Scott Wright, M.D., leads regulatory affairs efforts, including IRB review, for the task force. This work was the highest priority. "Our IRB team met every day, often at night and on weekends. Early in the pandemic, we worked around the clock to make sure studies received thorough and speedy reviews."
Accelerated activation and close collaboration: Mayo’s Office of Clinical Trials helps research teams start their studies and keep them running smoothly. This involves careful coordination between investigators, study staff, research coordinators, and other specialty areas such as pharmacy and radiology. To keep COVID-19 trials moving at top speed the office re-tooled its usual process into a streamlined “fast track.”
"We approached these trials as one and proactively addressed issues that we’ve learned from experience can sometimes cause delays or rework in clinical trials," says Andrea Kukla, a project manager in the Office of Clinical Trials.
Specialized nursing teams, on the move: Mayo’s Clinical Research and Trials Unit fields a crew of nurses specially trained to support clinical trials. To accommodate COVID-19 demands, the unit created a core team focused solely on COVID-19 trials, all under the oversight of a unit coordinator. This approach ensured the team could handle the high patient volume and pace of the work while maintaining consistency and efficiency. The nursing team was trained in specialty techniques, including nasal swabbing, wearing the correct personal protective equipment, and administering experimental medications.
“No two protocols were alike,” recalls Holly Tuseth, a nurse manager in Mayo’s Clinical Research and Trials Unit, “so we developed procedures for each specific patient visit and needed to make sure each detail, sometimes down to seconds, was followed to ensure the integrity of the data collected.”
The Clinical Research and Trials Unit has two dedicated locations at Mayo Clinic in Rochester: one for inpatient studies, one for outpatient studies. However, the volume of patients and the logistical requirements of COVID-19 care made it impossible ask patients to come to the unit —so instead the unit mobilized its nurses, sending them out into the hospital to work directly with patients and their care teams.
Study data at the ready: To keep track of all of the activity, the Clinical Research and Trials Unit introduced a "big board," like a departure and arrivals board at an airport, to track research activities in real-time.
"Research nursing staff were able to track the next research activities to be conducted for all COVID-19 study patients," says Jenny Weis. "You could see at a glance what needed to be done next for each study participant and remain apprised of their exact location at the hospital."
What the CTSA Program is all About
Mayo’s Center for Clinical and Translational Science is funded by a grant from the National Institutes of Health Clinical and Translational Science Award (CTSA) program. The program funds clinical and translational research at more than 50 academic medical centers across the United States. Dr. Lucchinetti says the lenzilumab study "reflects the ability of CTSAs to help remove barriers in order to accelerate the advancement of medicine from bench to bedside.
"This study was built upon an observation in the laboratory, which led to a pilot study followed by a phase 3 clinical therapeutic trial, all within one year from concept to execution. This is a remarkable example of innovation and teamwork, leveraging the CTSA integrated infrastructure," Dr. Lucchinetti says.
Is This a Peek Into the Future of Clinical Trials?
The pandemic forced researchers to innovate, adopting digital and virtual tools, and Dr. Lucchinetti predicts those tools are here to stay.
"There are many redundant clinical trials occurring across the country, and it’s not necessarily the most coordinated, optimal way to test the validity of these trials," she says. "The coordination we saw at Mayo Clinic exemplified by CCaTS and the SARS-CoV-2 COVID-19 Research Task Force gives insight into what could be possible if that were scaled at a national level."
— Caitlin Doran, June 2021
Read more about the Cancer to COVID-19 research in, "Cancer to COVID-19: Experimental Treatment Pivots in Record Time."