July 27, 2020 | In January, Elizabeth (Beth) Fox, MD, was recruited from the Children's Hospital of Philadelphia where she was the director of the developmental therapeutics program in oncology, to take on the role of Senior Vice President of Clinical Trials Administration and the Associate Director for clinical research within the St. Jude Children’s Research Hospital Comprehensive Cancer Center.

Three months later, St. Jude has voluntarily suspended accrual to more than 500 observational studies in response to the COVID-19 pandemic.

While the short-term impacts of the pandemic have certainly slowed clinical research, Fox keeps a long view. Clinical Research News editor Allison Proffitt recently spoke with Fox about her goals for her new role both before and after the pandemic began. During the pandemic, St Jude Children’s Research Hospital has continued its interventional treatment trials for children and adolescents with cancer and catastrophic disease. And now some of Fox’s initial goals for her tenure at St. Jude—including an expanded clinical infrastructure and informatics—are more important than ever.

“COVID-19 has created a broad range of challenges in all aspects of our lives. It has changed the way we conduct clinical trials because in addition to providing new therapies, evaluating causes of diseases, or late effects of the therapy, we must consider the possible impact of research on the spread of COVID-19 to patients, families, staff and in the community,” Fox said. “I am thrilled to be at St Jude because the entire institution is dedicated to care of children and families and research to improve the health of children.  The entire community of St Jude has come together and will continue to adapt to necessary safety measures to continue our mission during this pandemic.”

Clinical Research News: It’s been a really unusual time in which to start a new position. Thinking back before the pandemic, why did you move to St. Jude? Why Philly to Memphis?

Beth Fox: It is an extraordinarily interesting time in drug development for cancer and in all clinical trials for children with catastrophic diseases. There are increased efforts to get drugs for children into clinical trials faster, and there are more drugs to be tested—that is particularly true in oncology. What drew me to St. Jude was a fantastic collaboration between basic, translational and clinical research. In my opinion St. Jude Children’s Research Hospital is extraordinarily well-positioned to make a major difference in drug development for children and therapies for all children, particularly in oncology.

The Race for Children Act will be fully enacted on August 18, 2020. That requires pharmaceutical companies who are developing cancer drugs for tumors with molecular targets to test and evaluate the drug in children, if the target exists in cancers that occur children. The RACE for Children Act has the potential to fundamentally change the landscape for how pharmaceutical companies prioritize clinical trials in the pediatric population. Will there be more agents to study and can we evaluate the most promising agents in children with cancer?

However, as we think about using molecularly targeted agents in childhood cancer, we know that cancers that occur in children have fewer molecular changes, therefore, fewer molecular targets, compared to cancers that occur in adults. Childhood cancer is a rare occurrence compared to the number of adults with cancer. This makes the population of children who need these therapies very small. A major strength of St. Jude is the ability to consider international trials: to conduct trials not only in the U.S. but collaborate with sites in Australia, in Canada, in England, in Europe and others places around the world.

Just to find the volume of patients needed for clinical trials?

Yes. To provide some scope, compared to adult cancers, there are many fewer children with cancer. It's estimated that the number of women who are living with metastatic breast cancer in the United States right now—today—is approximately 160,000 women. One cancer type, one stage, women in one country. It is also estimated that that same number—160,000—is the number of new cases of cancer worldwide in children. That encompasses all of the different cancers and stages of cancer in children.

In order to evaluate new therapies, we need to make sure that the new therapy is safe and then we need to determine if the treatment is effective. This is done in clinical trials and requires selecting the appropriate patient population to study the new therapy and closely evaluating the patient for side effects of the therapy and effects on the cancer. Clinical trials prescribe the therapy, order the necessary laboratory tests and evaluations for safety, and determine how the effect of the therapy on the cancer will be assessed (imaging studies, more marrow procedures or other tests), and the magnitude of effect that is considered meaningful or beneficial to the patient.

I know that St. Jude's facilities are incredibly world-class. When you are looking at running studies like you're describing, you've got kids literally all over the world with an extreme variation in the facilities that they have access to. Are you bringing those children to Memphis all the time? Are you working with partners worldwide? A site may only have one kid; a country may only have one kid! How do you make sure that you are keeping consistency across these studies?

Dr. Carlos Rodriguez-Galindo is the head of Global Pediatric Medicine at St. Jude, a department focused on children with cancer and other catastrophic diseases around the world. He and his team are working with many countries, institutions, and centers to help support health systems with novel approaches, best practices and a sense of shared purpose. Working with Dr. Rodriguez-Galindo and Dr. Victor Santana, we envision expanding some clinical trials sponsored by St. Jude to international collaborations.  We have been successful with some clinical trials for children with brain tumors or leukemia in collaborating with institutions in Canada, Australia, New Zealand and United Kingdom. In these collaborations, patients are treated at centers in their home country.  The trials are supported and monitored by St. Jude. Working together, we would like to expand this effort to ensure that children who have cancer progression because of specific molecular changes in cancer cells have access to clinical trials of new therapies that target the molecular change.

COVID-19 has impacted how we monitor these clinical trials for safety in the US and abroad. We have teams of people who usually travel to centers where patients are enrolled to review the data and conduct of the trial to make sure that patients are safe. We apply the same quality standards that we have for the data for the patients treated at St. Jude in Memphis. Currently these reviews are being done with remote access. Using remote procedures, we are able to continue the multiple layers of review, external and internal, for oversight of the clinical trial to make sure that everyone is working together to ensure the trials are conducted safely.

When you came to St. Jude in January, none of us had any idea what this year was going to look like, but did you have a list of goals for your role at St. Jude? Did you have things that you wanted to prioritize, and if so how has that list changed?

In any new position, the first goal is to understand the environment to create a strategy that capitalizes on the strengths of the institution, while addressing challenges and creating a renewed vision for clinical research. One of my major goals is to consider how can we get new therapies to more children throughout the world sooner. Obviously with COVID-19 that goal is in the planning stages.

Another goal is enhancing the infrastructure for clinical trials here at St. Jude. That involves using informatic technology systems for tracking studies, for data entry and for monitoring patients on studies. Work toward this objective has been able to continue. We have a team of experts in the Clinical Research Informatics Systems Program who help us understand and fully utilize data and informatics systems to improve clinical research and the patient experience. We are working to integrate the systems and train research study teams on these systems so we can be more cost effective, efficient, and have more patients participate in clinical research before, during, and after treatment.

In addition, I plan to work with investigators to design and conduct innovative clinical trials for innovative therapies discovered in St. Jude research teams and in collaboration with pharmaceutical industry partners and our cooperative clinical research network.

It sounds like that particular goal has never been more important. This seems like the absolute best time to be able to track your studies and your data and monitor patients in an informatic system that is very robust.

Absolutely. In the current pandemic situation, investigators understand the value of those types of systems. Change is always hard, but it helps to see, “Wow, we can remotely monitor our sites successfully and can keep up with the data.” We are hoping we can use this experience to improve the efficiency and cost effectiveness of monitoring.

I think one of the challenges for all sites—here at St. Jude main campus and all of our collaborating and affiliate sites—has been staffing. When the COVID-19 pandemic came, much of our staff was transitioned to remote working. That was true for a lot of hospitals. So who's putting in the data? Who's seeing the patients? Who's tracking the patients? Who's making sure the protocol is followed? All of the very important people—the clinical research associates, the clinical research nurses, investigational pharmacists—we had to carefully decide who could be on campus and who couldn't.

We were very fortunate at St. Jude, due to the diligent work and creativity of a lot of people, that we were able to continue enrollment to our treatment studies for children, not only with cancer, but all of the catastrophic diseases that we treat here at St. Jude. That was a primary goal because for children who have catastrophic disease or cancer, often these clinical trials are the best way to treat patients. They are, in many ways, the standard of care, especially for those children who have relapsed cancer or very high-risk cancer. It became my personal priority and the priority of the institution to be able to treat those children on those clinical trials where there was the prospect of direct benefit to the patient.

However, we couldn't do all of the exploratory or all of the planned secondary objectives of the clinical trials. The primary objective is often to treat the disease; secondary objectives include very important endeavors like psychosocial interventions and laboratory research to help understand the disease. Those secondary study aims and objectives were put on voluntary hold for the vast majority of our studies and all of our studies that are non-therapeutic: non-interventional studies, observational studies, or surveys to understand important aspects of patient care were put on voluntary hold to decrease the risk of transmission of COVID-19.

Like many centers that treat children with cancer, our patient numbers initially decreased, especially in April and early May. In June and July, the number of patients we're treating on therapeutic trials is coming back to normal. We're also just beginning to allow patients to enter the other types of trials (non-therapeutic studies) that don't have a treatment associated with them if those studies can be done completely virtually through telehealth technology and without any additional research-only visits to the hospital. This is a way to safeguard our patients, our families, and our staff as best we can during this time. Fewer exposures is better for everyone; fewer touchpoints in the hospital is critical. We carefully look at what is involved for the patient and family, how much time is needed in different areas of the hospital, and how many staff have to be here in order to conduct this study before we decide if we can allow that study to reopen.

How many observational studies did you have to put on hold?

Over 500.

Wow. Are those data lost because all of the participants kept on living and progressing in whichever ways that they were? Or are those studies salvageable?

The data is not lost but it is delayed. We put the study on hold to new enrollments, but we try to maintain the data integrity for patients who were already enrolled. The best example of this is the St. Jude LIFE Study (SJLIFE) conducted under the direction of Dr. Les Robison, Dr. Melissa Hudson and the Cancer Control, Survivorship and Epidemiology Programs at St. Jude. St. Jude LIFE is ongoing for patients and people who've survived cancer; however, accrual of new survivors and planned follow up evaluations have been on hiatus since March. Survivors of cancer, who are eligible to enroll on that study, have not been able to participate. We are hopeful that when things become more stable with COVID-19 infection rates, we will be able to enroll them. A few months’ delay getting them enrolled is not as big of an issue for the study and its objective as it would be for a treatment study where you have to treat the patients when they have new or recurrent disease.

In discussions with Dr. Robison, he feels that the in-depth evaluations done on the St. Jude campus are critical to the value of the patient experience as well as the data that identifies needs of survivors and informs our understanding of the side effects of therapy that survivors of childhood cancer experience. He considers the delay appropriate to make sure we protect the patients. However, St. Jude investigators are conducting some studies in pediatric cancer survivors by utilizing telehealth and other virtual communication tools that do not require people to travel to campus.  We are doing our best to adapt to the changing needs of clinical research and patients during the COVID-19 pandemic.

Where did decreased enrollments come from in May? Were there less patients being diagnosed? Were there less patients choosing to travel or being invited to travel to the facility? Does that mean that we've missed a window of opportunity for a lot of cancer patients?

I think probably a little bit of many of the things you mentioned. Back in April, May and the early part of June there was discussion in pediatric oncology clinics around the country that numbers of patients with newly diagnosed cancer had decreased. We know the incidence of childhood cancer has not decreased. We are concerned—and there are a couple of case reports in the literature—that there was a reluctance on the part of both families and the physicians to bring children into emergency rooms for evaluation and many routine doctor’s appointments were canceled or postponed due to COVID-19. Our concern as a community of oncologists was that disease is more progressed when the child presents with more serious symptoms. It complicates diagnosis and treatment if the child is very ill at the time they are first evaluated.

At St. Jude, we can sponsor patient travel to treat children on clinical trials at St. Jude. Concern about patient travel did play a role in decreased numbers of children evaluated at St. Jude in the Spring.  We encouraged children and families to be evaluated at institutions closer to their home, rather than having them travel and potentially be exposed to COVID-19 at airports.

The whole situation is multifactorial. It will take decades probably to tease apart how it all works together. But that said, from your perspective now, do you foresee changes in how St. Jude conducts clinical trials, how the entire industry conducts clinical trials on the backside of this? Are you seeing long term improvements that we can make?

I hope that there are improvements and we can make some positive changes.  For example, clinical trials administration and many clinical research teams are currently working remotely. There are many people behind the scenes for every clinical trial.  We use web conferencing and other platforms to stay in close communication. Team members including the clinical trial budget and finance team, the informatics team and many of the individuals who manage data and review of clinical trials have been very effective and productive working from home to support clinical trials at St. Jude.

From the patient and trial perspective, restrictions, regulations and licensing for telehealth were eased during COVID-19. It would be beneficial to continue to be able to use telehealth more, especially for clinical trials. Here at St. Jude, when patients travel we provide housing for those patients. We've been able to deliver some of the care in housing with nursing visits. That has helped the patients, but also helped make sure that we could monitor patients for side effects of new therapies and that the clinical trials were done safely, without having patients and families come to the hospital.

I hope that some of the modifications to conduct of clinical trials that we introduced during COVID-19  can become permanent, particularly for the patient experience of clinical research. Careful consideration of extra visits to the hospital for research or laboratory testing should be assessed . An increased reliance on telehealth could make a big difference in the amount of time that clinical trial participants are required to be at the hospital.

Clinical trials are means by which we demonstrate that new treatments are safe and effective.  They are  critical to improving the outcomes for children and adolescents with cancer, blood disorders and other catastrophic diseases.  We will continue to adapt to support the safe conduct of clinical research during the COVID-19 pandemic.