Launching a multisite clinical trial in the midst of a pandemic
In early March 2020, as it became clear the novel coronavirus was closing in on Southern California, clinical trials leaders from the Department of Research & Evaluation began assessing options for an investigational treatment that could be studied through clinical trials. With no approved medications to fight COVID-19, the need for an investigational option to offer our patients was felt to be imperative.
“We knew we needed an option that was in late-stage development so we could get the medication to as many patients as possible. And we also realized that in a pandemic we would need to open this study at as many of our Kaiser Permanente Southern California medical centers as we could,” said William Towner, MD, FACP, FIDSA, principal investigator for the trial and regional physician director of the Division of Clinical Trials Research.
It quickly became apparent that an antiviral drug, remdesivir, met these criteria. Dr. Towner and Hai Linh Kerrigan, PharmD, division research administrator for clinical trials, approached the manufacturer with a proposition—open their clinical trial in multiple Kaiser Permanente Southern California sites simultaneously, and under expedited processes.
And so began one of the largest clinical trials in Kaiser Permanente history. Within 9 days of that first conversation, the first Kaiser Permanente Southern California study patient was enrolled. Just 2 months later, physician investigators had enrolled more than 500 patients hospitalized with severe COVID-19, making Kaiser Permanente Southern California one of the top-enrolling sites for the clinical trial in the world. The research team had also laid the foundation for an inpatient multisite clinical trials network that could serve as a template for future pandemic clinical trials research.
Building infrastructure to enroll hundreds of patients across Southern California
Enrolling more than 500 subjects in trial sites spanning 15 Southern California hospitals took a herculean effort from the clinical trials team and many others within the Department of Research & Evaluation, Southern California Permanente Medical Group infectious disease specialists, and Kaiser Permanente pharmacy operations. To put the numbers into perspective, that’s about how many patients would be enrolled in all clinical trials across the region in a typical year.
One of the earliest steps was to develop a web-based enrollment system that would allow investigators at all the Kaiser Permanente sites to refer patients to a command center, where they could then be screened by a research coordinator. The system, developed by the Department of Research & Evaluation’s IT team, also would serve as a centralized tracking system for all enrolled patients to support screening and ongoing follow up.
Additionally, IT configured more than 75 iPads to assist in an all-electronic, paperless consent process, which was necessary to meet infection control standards mandated because of COVID-19. Clinical trials team members and other volunteers from the Department of Research & Evaluation drove across Southern California to distribute the iPads to each medical center.
The team also had to coordinate inventory and dispensing of study medication with 15 inpatient pharmacies across the region. This included development of study-specific drug order entry panels in Kaiser Permanente HealthConnect®.
Standing up a regional command center to coordinate enrollment across all sites
Once the essential IT infrastructure was in place, the work of coordinating enrollment across multiple sites began in earnest. The team launched a Clinical Trials Command Center, staffed 7 days a week, including holidays, from 7 a.m. to 7 p.m.
The team created a rotating split shift of 10 research coordinators to work with more than 60 investigators to screen and enroll each patient. More than 50 staff members have been assigned to support the command center as part of the ongoing clinical trial.
Meanwhile, the clinical trials regulatory affairs team manages the numerous federal and state, Institutional Review Board, and sponsor regulatory requirements and document submissions that were needed for this clinical trial. They also handle internal data quality assurance for Kaiser Permanente Southern California’s online research information system.
Tapping into resources across the department to manage massive data requirements
Most clinical trials require an enormous amount of data be entered into the sponsor’s database, including labs, adverse events, concomitant medications, and medical history. This trial is no different in the volume of data per patient. But the number of patients, frequency of study timepoints, and the pace at which they are enrolled, creates a new challenge.
The Department of Research & Evaluation’s statistical services group provides vital support for this effort, pulling data electronically every night for all study labs and adverse events.
More than 80 staff members from divisions across the research department are supporting the effort to enter data into the sponsor’s data entry system. As of mid-May, staff had entered more than 40,000 case reports. The pharmacy team also supports data entry by providing clinical data and guidance.
A separate team was created to record and enter adverse events into the electronic data capture system. Yet another team addresses thousands of sponsor-related queries.
Finally, a group of 14 ambulatory care pharmacists serve as a safety net to clinically monitor subjects to ensure that lab tests are performed as specified by the protocol and to confirm study medication is stopped if needed for a safety reason.
Recognizing the role staff across the department have played in achieving success
About 150 research staff members from every division in the Department of Research & Evaluation are leaning in to help with the effort.
“I have continued to be amazed by the dedication and passion of our research staff toward finding a treatment that helps patients afflicted by COVID. They are all heroes,” said Dr. Towner.
While the work has been complicated, the motivation is simple: a desire to help our patients.
“We have always considered clinical trials to be more than just ‘research,’” said Dr. Kerrigan. “This study is providing a potential treatment option to our severely sick patients who do not have any FDA-approved treatments available. It has been truly a privilege for our department to be able to offer this medication to our patients during this pandemic.”