Pandemic has provided lessons on continuing research during a crisis

COVID-19 has been a tragic wrecking ball on several fronts, but something that isn’t mentioned much is clinical research.

Long a linchpin at CHOC and, moving forward, poised to become even more central as CHOC evolves into a leading pediatric health system, clinical research has had to quickly readjust under the strain of the pandemic.

But out of these dark days have emerged several lessons on not only how to continue research during a crisis, but how to keep it thriving.

That was a key message delivered by Phuong Dao, director of Research Operations at CHOC, during a recent webinar beamed around the country.

Phuong Dao, director of research operations at CHOC

“There’s a renewed sense of energy and purpose to use science to solve problems that are important to our patients and the public,” Phuong said during a panel discussion that was part of a two-week summit on rare diseases hosted by Global Genes, an Aliso Viejo-based non-profit that advocates for the rare disease community.

“I think we can really harness and leverage this shared renewed energy and translate that to the conducting of rare-disease trials,” Phuong said.

The panel, speaking on “Proactive Planning for Continuity of Research During a Crisis,” also featured moderator Nina Wachsman, founder and president of Augur Health, a New York-based clinical research recruitment firm, and Gerald Mosely, founder and principal of CP&P Development, a Sacramento-based specialty consulting firm focused on pharmaceutical sales and operations.

Wachsman laid out some realities hospitals face during COVID-19:

  • Less access to doctors and inpatient visits
  • Less interest in research into rare diseases
  • An explosion in telehealth visits
  • E-signatures for informed consent
  • Nurse home visits
  • Lab tests done remotely

As for clinical research, Wachsman said, challenges include a lack of available capital, a lack of access to enough clinical trial participants and the ability to retain them, and getting the attention of the FDA at a time when COVID-related studies dominate.

And in a world of virtual meetings, Mosely noted, effective teamwork can be a challenge.

“The people aspect is what can make or break things,” Mosely said. “Successful outcomes can be affected more by interpersonal than technical skills.”

But bright spots abound, Phuong said.

COVID-19 studies can serve as a template for clinical research well beyond the end of the pandemic. “We have seen study teams form quickly and multi-disciplinary teams mobilize,” she said.

The contracting and budgeting processes for COVID-19 studies have accelerated and teams involved in “master trial protocol” studies involving multiple hospitals have readily shared resources, when in the past there were more hurdles.

“This focus on leaner and faster clinical trials can be leveraged in the rare disease space as well,” Phuong said.

Other positive changes introduced during the pandemic that can affect all clinical trials moving forward include:

  • Fast tracking by the Institutional Review Board (IRB)
  • The acceptability, and patient popularity, of telehealth
  • Home-based testing and monitoring technologies
  • Curbside/courier pick-up and delivery of participant samples and investigational products
  • Digital data collecting tools
  • Remote Site Initiation Visits (SIVs) and monitoring
  • Less reliance of participants having to be on site

Phuong noted that clinical trials involving kids impact entire families, one of the things that makes pediatric research different from studies involving adults.

The consenting process is unique, she added, and some teenagers who still are minors sometimes have a different opinion from their parents when it comes to treatment plans.

Moving forward with telehealth, Phuong said, clinicians need to think about how to engage with study participants in the languages they understand best.

And there are other questions that need to be addressed, including:

  • How research should be structured to adapt to new realities
  • How to keep motivation high to conduct clinical studies into rare diseases
  • How virtual meetings and healthcare visits affect productivity

“I hope that we sustain the gains we have made to move toward more efficiently and that we are able to approach clinical research in ways that are more streamlined and modernized,” Phuong said.

To learn more about CHOC’s Research Institute, click here.

How COVID-19 survivors can support others through plasma donation

For Steve Emfinger, donating his blood plasma at CHOC Children’s was fast, painless and a way to give meaning to his battle with COVID-19.

“It was very simple,” he said. “And to know it’s helping kids is very cool.”

Man donates plasma to help COVID-19 patients
Steve with his COVID-19 convalescent plasma donation at CHOC Children’s Blood Bank.

Registered with the U.S. Food and Drug Administration, the CHOC Children’s Blood Bank is available to collect and process blood plasma donations from COVID-19 survivors. These donations are being used to help patients at CHOC and throughout the community.

“We’re still learning about COVID-19, but it’s possible that those who have recovered from the disease have produced antibodies to protect them from the infection,” says Dr. Antonio Arrieta, a pediatric infectious disease specialist who is studying the use of convalescent COVID-19 plasma at CHOC. “If so, their blood plasma would contain these antibodies and may be helpful in the treatment of COVID-19 disease in others.”

Since CHOC began collecting and processing blood plasma donations from recovered COVID-19 patients this spring, more than a dozen CHOC patients have benefited.

And as COVID-19 diagnoses continue to mount in Orange County and fall approaches, the need for blood plasma donations will only grow at CHOC, Dr. Arrieta says.

A surprising diagnosis

Typically, an early riser with boundless energy, Steve just felt zapped in late winter. Attributing the lethargy to two back-to-back trips he’d just taken, Steve decided to work from home. 

Though his symptoms – including a slight cough and dizziness – were minor, Steve’s energy shift was so atypical that he ultimately decided to go to a local hospital. There, he was tested for the flu and strep throat and had a chest scan, which all came back negative.

Steve had one more test – for COVID-19. A couple days later, he got word the test was positive.

Steve hunkered down at home, and notified any friends, family and neighbors he’d been in contact within the weeks before his diagnosis. Some days he felt good – able to work remotely and cook meals – and others were much more challenging.

All in all, though, Steve felt fortunate to have mild symptoms, never experiencing a fever, body aches or significant respiratory problems, despite a lifelong mild case of asthma.

“I think I’m blessed to know that I had minor symptoms and was able to get through it and my family didn’t get sick,” he says.

As Steve’s diagnosis came early into the pandemic’s spread in Southern California, he was initially reluctant to share his story with a broader network of friends, family and colleagues. But as he got more comfortable, Steve’s decision to tell others proved fortuitous.

A friend who worked at CHOC told Steve about the COVID-19 convalescent plasma program and how badly donations were needed.

“I had heard that blood plasma was needed, but I didn’t know where to find a donor center,” he said. “I called CHOC the next day to make an appointment.”

The process to donate plasma to support COVID-19 patients
Steve has already donated plasma twice at CHOC Children’s to help support others fighting COVID-19.

Steps to donate

Potential donors must meet some criteria to be eligible:

  1. Donors must show laboratory test proof of their COVID-19 diagnosis either through a diagnostic test (nasopharyngeal swab) at the time they were sick, or a positive serological test for SARS-CoV-2 antibodies after they recovered.
  2. Donors must have been symptom-free for at least 14 days before they donate.
  3. They must meet all other health requirements for blood donors.
  4. Though donors may be male or female, female donors will need to meet some additional requirements that the Blood Bank team will help explain further.

Confirming these requirements takes about a week. Once donors are confirmed and at the Blood Bank, the simple donation process takes about two hours. Donors can return every 28 days to donate again.

Steve is already on his second donation at CHOC and plans to continue in the future – in addition to donating blood and platelets.

“To help someone else makes it all worth it,” he says.

To schedule an appointment or learn more, call the CHOC Children’s Blood Bank at 714-509-8339.

Rapid genome testing for infants saves lives, costs

Its name conjures up images of a familiar fairy tale, but Project Baby Bear has produced some very impressive real-world results that could save the lives of thousands of seriously ill infants.

The recently completed two-year pilot program at five clinical sites in California – including CHOC Children’s – helped doctors target a baby’s specific genetic disease in a matter of days, instead of the four to six weeks required for standard genetic tests.

That means quicker diagnoses leading to quicker treatments, less time in the hospital and more answers for anxious parents.

“It can be a real game changer,” said Dr. Jason Knight, a pediatric critical care physician and medical director of CHOC’s pediatric intensive care unit and one of the physician leads on the project. “It’s a tool we didn’t have a few years ago.”

Changing the game

By employing rapid whole genome sequencing (rWGS), doctors could gather vital information that changed the decisions families and clinicians made, and ultimately saved lives and resources. The procedure has historically been used only as a last resort.

By pinpointing the cause of rare disease with rWGS, physicians can customize treatment. And having a genetic diagnosis can eliminate the need for further tests, improve outcomes, reduce hospital stay length and improve the experience of care for families – all while also reducing costs.

In addition, substantial reductions in healthcare spending — $2.5 million — accrued largely because rWGS permitted doctors to discharge babies sooner and reduce the number of procedures that may have been performed in the absence of a precise diagnosis.

Avoided procedures included 11 major surgeries and 16 fewer diagnostic tests such as  open muscle, liver and other biopsies that are performed under general anesthesia.

Success story

In one case, a newborn baby girl with a life-threatening irregular heartbeat was admitted to CHOC Children’s Hospital. Instead of undergoing an arduous battery of tests, the child was diagnosed within two days with Timothy Syndrome, an extremely rare cardiac condition that put her at risk for sudden death.

With the genetic diagnosis in hand, CHOC physicians were able to treat the infant with the appropriate medication  for her condition. Her heartbeat was restored to normal, significantly reducing the risk of sudden cardiac death. Her physicians, secure in her diagnosis, implanted a pacemaker, dramatically improving her chances for a happy and healthy childhood.

She recently celebrated her first birthday.

“Without the results of her rapid whole genome sequence, she would have gone home on a different medication and been at a much higher risk for sudden death,” Dr. Knight said. “She got the right diagnosis and we gave her a pacemaker so her risk of sudden death went to zero.”

In all, Project Baby Bear provided diagnoses for 76 of the 178 babies who completed rWGS. This led to a change in the care of 66 babies. It diagnosed 35 rare conditions that occur in less than one in 1 million births. About 150,000 children could benefit from rWGS.

Turning every stone

Even if the test doesn’t diagnose a problem, it can help comfort families, Dr. Knight said.

“Even a negative test can be helpful for some families to know we’re not missing something,” he said. “It gives them assurance that we’ve turned over every stone.”

With the success of the study, Dr. Knight hopes to see the service expand to reach more patients.

“Should we be doing this with all newborns?” he asked. “Based on our experience with Project Baby Bear, it would seem feasible that for newborns and children in intensive care units without clear diagnoses, this should be part of our diagnostic process and the earlier the better.”

Multidisciplinary, multi-site effort

CHOC’s role in Project Baby Bear is a collaborative, multi-disciplinary effort involving many clinicians and staff, including research coordinators Cathy Flores, Erum Naeem and Ofelia Vargas-Shiraishi, and physician leads Drs. John Cleary, Juliette Hunt, Adam Schwarz and Neda Zadeh, in addition to Dr. Knight.

Led by Rady Children’s Hospital-San Diego, Project Baby Bear helps infants who are undergoing intensive care and covered by Medi-Cal. The other participating hospitals include UCSF Benioff Children’s Hospital Oakland, UC Davis Children’s Hospital in Sacramento, and Valley Children’s Healthcare in Madera.

The $2 million Project Baby Bear was funded by the State of California. In-kind contributions of $400,000 from Rady Children’s Hospital ensured more than 90 percent of the state funds were used to support the care and management of critically ill babies.

Learn more about the CHOC Children’s Research Institute.

The forefront of CAR T-Cell immunotherapy research for high-risk pediatric leukemia patients

Innovative research conducted at the Hyundai Cancer Institute at CHOC Children’s includes investigations into immunotherapy, which has emerged as an effective therapeutic modality for patients with hematologic malignancies. Chimeric Antigen Receptor (CAR) T-cell therapy is capturing the attention of the medical community as a prominent example of cellular immunotherapy and is often referred to as a “living drug.”

“CAR T-cell therapy has revolutionized the treatment landscape of relapsed or refractory B-cell acute lymphoblastic leukemia (ALL) — a disease that was historically considered to have a very poor prognosis,” says pediatric oncologist Dr. Van Huynh, who leads the CAR T-cell program at CHOC “With this remarkable approach, we are able to harness the patient’s own immune system to potentially cure their leukemia.”

Dr. Van Huynh, pediatric oncologist at the Hyundai Cancer Institute at CHOC Children’s

CHOC was one of the first pediatric sites for CAR T-cell therapy clinical trials in 2015. Along with providing access to innovative clinical trials for CAR T-cell therapy and other immunotherapy, CHOC is now a certified treatment center for providing the recent U.S. Food and Drug Administration-approved CAR T-cell therapy called KYMRIAH. It is available to pediatric and adolescent/young adult (AYA) patients who are up to 25 years of age with second or later relapse or refractory (R/R) B-cell ALL or patients with R/R large B-cell lymphoma.

CAR T-cell therapy involves the collection of a patient’s own T-cells and genetic modification of these cells to express a CAR that can recognize a tumor antigen such as CD19 on leukemia cells. The CAR T-cells are then expanded in the lab and later re-infused back into the patient, where they continue to expand and seek out the target antigens to eradicate the leukemia.

CAR T-cell therapy has given hope to many patients who otherwise had no other treatment options. Furthermore, dramatic initial clinical responses and high rates of complete remission have been observed. Relapses can occur due to antigen loss (leukemia cells no longer express the target antigen) or CAR T-cell exhaustion (the CAR T-cells no longer provide protection).

“Currently, researchers are looking into ways to overcome these two barriers to make this therapy even more effective,” Dr. Huynh says. “I’m also excited for the potential of CAR-Ts to target other antigens besides CD19 and the possibility that it may be able to treat other types of cancer.”

Our Care and Commitment to Children Has Been Recognized

CHOC Children’s was named one of the nation’s best children’s hospitals by U.S. News & World Report in its 2020-2021 Best Children’s Hospitals rankings and ranked in the cancer specialty.

Learn how CHOC’s pediatric oncology treatments, expertise and support programs preserve childhood for children in Orange County, Calif., and beyond.

CHOC, University Lab Partners establish unique training program for the next generation of biotech innovators

The CHOC Children’s Research Institute and University Lab Partners (ULP) have jointly developed a new science, technology, engineering, and mathematics (STEM), medical innovation and entrepreneurship program geared toward inspiring Orange County high school students to become the next generation of biotech innovators. 

Through the Medical Innovation and Entrepreneurship program, students will work alongside Orange County’s top leaders in innovation and medicine to gain a real-world view of the multidisciplinary skills needed to thrive in the biotech entrepreneurial world.

The program takes students on a journey from idea to innovation, while gaining the understanding of what is required to implement their vision. Student teams will work with industry mentors to solve real-world unmet clinical needs presented by CHOC clinicians, devising a proof-of-concept, an IP and patent strategy, and exit plan that they will pitch to industry leaders on the final day.

Through pediatric-focused case studies, customized lesson plans, team project work, and mentor opportunities, students will identify real-world solutions to issues that directly impact pediatric patients. Students will learn the role a clinician and engineer play as they navigate unmet clinical needs, hospital systems, care providers, and regulatory trends required for healthcare innovation.

In addition, The Young Entrepreneur OC will foster the next generation of leaders through the transformative experience of building a startup. While teaching the skills to build and lead a company, the program also coaches young people to identify and leverage successful pathways to reach personal and professional goals.

“The CHOC Research Institute is thrilled for the opportunity to help inspire the next generation of leaders in healthcare innovation, potentially laying the groundwork for great strides in translational science, medical device development, and basic science research,”  said Dr. Terence Sanger, CHOC’s vice president of research and chief scientific officer.

During the two-week program delivered through the North Orange County ROP, 60  students from five different school districts will learn the business of medtech and biotech through 50 hours of instruction, 10 hours of dedicated mentorship, and 20 hours of clinical needs assessments, project proposals/presentations, literature reviews, and intellectual property challenges. Students will earn 2.5  UC-transferable credits for their participation.

“By connecting our most precious commodity, our students, to businesses who will invest in them, this partnership benefits us all,” said Dr. Terri Giamarino, superintendent of NOCROP. “We want our students to remain in Orange County and be a part of our growth and sustainability.”

Said Dr. George Tolomiczenko, director of medical innovations at University of California, Irvine: “Clinical needs can take many forms in a healthcare setting. Success in meeting an unmet need relies on understanding the target disease, its underlying etiologies and subgroups. I’m looking forward to teaching these high school students how to refine an unmet clinical need.”

The Medical Innovation and Entrepreneurship High School work-based learning program is one of many projects that will launch from the partnership between the CHOC Research Institute and University Lab Partners. The effort brings together clinical skills, business development skills, hospital management, technology strategy, product ideation, and technology development to help support the larger Orange County biotech and medtech community.

“This partnership is a powerful collaboration that will help generate the energy needed to transform the healthcare industry through leading technology products and platforms. This immersive program transforms career exploration and discovery for Orange County students interested in pursuing an exciting career in innovation” said Karin Koch, ULP’s ecosystem director. 

Learn more about the CHOC Children’s Research Institute.