Matthew M. Cooney, M.D., Vice President, Medical Sciences, Parexel
Roberta Steere, MS, MBA, Sr. Solution Consultant Director, Early Phase, Parexel
Ally Bowen, Director, Project Leadership, Parexel
The World Health Organization states that COVID-19 has infected over 750,000 people in 203 countries as of March 31, 2020. China and the United States, two of the countries hardest hit by COVID-19, are, coincidentally, the global leaders in cellular therapy trials. Although there are multiple types of cellular therapy trials, TCR and CAR-T cell are leading the way. This pandemic creates complexities for patients, health care systems, manufacturing sites, and the industry partners who drive these trials.
Although not a perfect framework, to simplify the discussion, cell therapy trials can be grouped into three categories:
- Prior to first patient enrolled
- Open trials with active patient enrollment
- Enrollment completed and in final data collection and analysis
Trials Prior to First Patient Enrollment
As health care institutions grapple with how to respond to the COVID-19 outbreak, there are some central themes. Restriction of all “non-essential” activities are being instituted. These non-essential activities may include:
- Highly selective IRB reviews and deferment of non-essential trials
- Cancellation of Investigator Meetings
- Delay of Site Initiation Visits (or only offering virtual SIVs)
- Restriction of medical and radiological visits essential to trial
Overall, it will be exceptionally challenging to open new clinical trials during the COVID-19 pandemic. Exceptions would include studies directly related to diagnosis, treatment, or vaccination against the coronavirus. Certain cell therapy trials, with potentially major impact, may move forward at specific sites depending on resource availability. All other studies should anticipate delayed timelines, with regional variability, in opening cellular therapy trials.
Proactive measures to minimize delay are essential for trials that have not yet accrued a patient. Essential functions including site selection, finalizing trial documents, working with IRBs, and remote site initiation visits can keep the trial moving forward. Some current projections estimate the worst of the COVID-19 crisis may subside this summer. When this occurs, health systems may be flooded with delayed clinical care that has been put off for several months. Additionally, clinicians will need a well-deserved vacation to refresh. Trials that wait for the summer to begin site activation will be competing with a myriad of other factors that will likely delay launch of the project even further.
Open Trials with Active Patient Enrollment
Cancer patients who enroll in cellular therapy trials generally have life threatening illnesses for which delay of enrollment into a clinical trial may have disastrous consequences. Although there is an increasing number of solid tumor cellular therapy trials, the majority focus on hematological malignancies. These patients are already at higher risk for infection which may put them at risk for serious complications from COVID-19.
To make matters even more challenging, many of the larger centers that perform cell therapy trials are also on the front lines of battling the coronavirus. This puts additional strain on staff and hospital resources to enroll high-risk patients into a complex cell therapy protocol. Although the data is still early, we are anticipating significant slowdown, and in many sites a temporary pause in enrolling patients into cellular therapy trials. Effective strategies include regular phone calls with site principal investigators to learn about the local challenges. In our experience communicating with investigators, there appears to be a wide range of bandwidth for clinical trials. Over the next few weeks, more data will be available about accrual rates on cell therapy trials.
COVID-19 also puts manufacturing and logistics at risk for cell therapy trials. The labor-intensive manufacturing process is challenging with the recommendations for social distancing and encouragement for virtual work environments. However, heroic work is still ongoing from manufacturing and logistic vendors to ensure patient access to cell therapy products.
Enrollment Completed and in Final Data Analysis
Trials where the last patient has completed their clinical assessment have the best chance for on-time delivery. The availability of remote analysis and data preparation allows for minimal interruption. These trials may have a significant time advantage compared to competitive trials that are about to enroll, or are still enrolling, subjects.
Overall, this is an extraordinarily challenging time for clinical research. Patients’ access to the promise of cellular therapies is currently being affected by the COVID-19 pandemic. Strategically moving forward items that can be safely done will put the industry sponsor in the optimum position. Parexel has a full range of virtual solutions that can be incorporated into these trials whenever possible, to help minimize the disruption for cell therapy protocols.