Yale Center for Analytical Sciences (YCAS) observed its 10th anniversary this summer. Instead of celebrating, however, its staff worked harder than ever on a crisis where their skills and experience were desperately needed. “Routine” activities were augmented by efforts to help stem the COVID-19 pandemic that has taken more than half a million lives worldwide so far.
“We have been going non-stop since the start of the pandemic,” said Yanhong Deng, MPH ’10, senior biostatistician and co-director of analytics for the center, which is part of the Department of Biostatistics at the Yale School of Public Health. Biostatistics is the branch of statistics that works with biologic data.
Since March, the bulk of the center’s work has been helping with studies of therapies that could help combat the COVID-19 pandemic. The epidemic was not on the horizon when the center opened in 2010. But Deputy Director James Dziura, MPH ’98, PhD ’01, professor of emergency medicine and of biostatistics and of medicine (endocrinology) said it is ideally suited for this kind of public health emergency.
“We were prepared to deal with this. We have the resources to help design and conduct rigorous evaluations of research questions that relate to COVID-19,” Dziura said. He said YCAS has helped with 10 COVID-19 related therapeutic studies so far and is deeply involved with five of them.
A study that has just started will assess the effectiveness of an anti-viral drug called Camostat in treating COVID-19. Camostat is already used to treat pancreatitis. Participants in the study have COVID-19 but are not so sick that they need in-patient care at a hospital. The study illustrates the challenges of running clinical investigations in the middle of a pandemic. Patients require frequent in-person visits to assess viral load while quarantined and there’s a need to mitigate the risk of spread to other people, including the investigators themselves, Dziura said.
Then there is the challenge of finding participants. Investigators can choose a city where there are many COVID-19 cases for the study. But by the time they organize logistics, coordinate equipment and personnel, and are ready to start work, that location may no longer be a hot spot for the virus.
“It’s a fluid situation that makes conducting these studies a challenge,” Dziura said.
YCAS is also helping researchers find out if a new drug called sobetirome can protect the lung tissue of patients suffering from COVID-19. Naftali Kaminski, MD, Boehringer Ingelheim Pharmaceuticals, Inc. Professor of Medicine (Pulmonary), developed sobetirome several years ago to treat lung fibrosis. But after seeing that it might help with COVID-19 this spring, he and other investigators began preparing for the new study.
The COVID-19 pandemic is a time when the center can put the strengths of its staff to the best possible use. It is also an opportunity for them to learn. Dziura said he and other leaders at YCAS wanted to expand into investigations of new drugs and become experienced working on studies conducted under the oversight of FDA and other regulatory agencies. With governments and researchers scrambling to find effective treatments for COVID-19, the center now has a chance to do that, he said.
YCAS was established in 2010 to meet a growing need for statistical collaboration in clinical investigations fueled by the explosive growth in computer technology. Just five people worked there at the beginning: Director Peter Peduzzi, PhD ’76, Dziura, Deng, Fangyong Li, MPH ’10, MS, and Veronika Shabanova, PhD ’17, MPH ’99. Deng and Li had just graduated from the school of public health, and they are now co-directors of analytics for the center. Shabanova later went on to obtain her PhD at Yale.
"We had a pretty small shop when we started, but we saw a need to expand," said Dziura, an epidemiologist. And expand they did. The center now has 40 people on its staff. More than half of the staff at the center are biostatisticians like Deng and Li.
In the beginning, the center mainly helped investigators at Yale School of Medicine with data analysis. The center is now a leader in the field and its reach goes beyond Yale. Peduzzi said the center collaborates with other institutions in multi-site clinical investigations.
The center recently collaborated with researchers from 10 health care systems across the country on a six-year effort to find ways of preventing falls in the elderly population. Peduzzi said falling is particularly hazardous for older people and of those who fall, about 25% nationwide, 20 to 30% have such serious injuries as fractures. The National Institutes of Health and the Patient-Centered Outcomes Research Institute funded the investigation which had 5,451 participants at a cost of nearly $35 million. Other large, multi-site investigations involving YCAS include testing strategies for caring for people with dementia and testing nonpharmacological approaches for pain management in the U.S. Department of Veterans Affairs and Department of Defense health care systems.
"You need infrastructure to participate in these trials. Ten years ago, Yale did not have that," Peduzzi said.
“Biostatistics is an old field that keeps getting new,” Deng said. “And it’s growing fast because of advances in computer science.”
Gone are the days of putting your study results in an Excel spreadsheet. Now, ever more powerful computer programs collect and analyze vast amounts of data generated by clinical investigations.
"It used to be that you would have to wait for weeks to get results. Now we can deal with millions of pieces of data in seconds," Deng said.
In the past year, YCAS staff consulted on 854 unique projects with 457 Yale Center for Clinical Investigation investigators from 65 Yale departments/centers yielding 102 grant submissions and 162 publications.
Another component of the Center's work is helping investigators at the medical school comply with the federal government’s changing requirements for registering studies.
In the past several years, the Center has begun overseeing Yale’s compliance with mandatory federal clinical trial registration and results reporting on ClinicalTrials.gov. That website is maintained by the National Library of Medicine at the National Institutes of Health and the volume of studies that must be reported is increasing.
Jesse Reynolds, MS, a biostatistician, heads a team at the center that decides which studies at the medical school must register on ClinicalTrials.gov. He said that 1,100 of them are on the site so far.
The ClinicalTrials.gov website has existed since 2000. It is open to the public so researchers as well as patients and their families, can use it. Lisa Calvocoressi, PhD ’03, an epidemiologist with YCAS, said the website makes clinical investigations more transparent and effective.
“Trial registration and results reporting on ClinicalTrials.gov is one of the best things to happen to clinical research,” Calvocoressi said.
“In the past, people found out about new developments through articles published in journals,” she said. “But editors decide what does and does not appear in a journal and studies with positive findings are what tend to be published. But what about studies that do not have positive findings? Without those, you get a skewed view of how effective a drug may be. With access to the ClinicalTrials.gov, where all applicable trials are registered before they begin, we have a much more complete understanding and better transparency than we did previously.”
And there are the center’s many educational offerings for audiences ranging from professionals to high school students.
The center’s offerings include statistics courses for professionals and graduate students, mentorship of postdoctoral fellows, internships for graduate students, and an intensive two-week program for high school students—the Young Scholars Program in Biostatistics and Medical Research. Calvocoressi said the center is offering its Young Scholars program this summer. Previous sessions of the program were on campus and most students were from the New Haven area. But the center is holding it online this summer because of COVID-19 and students from as far away as India will participate. The program will augment its standard curriculum in biostatistics, computer programming languages, and research methods with guest speakers who are involved in ongoing COVID-19 research at Yale.
Even without the COVID-19 pandemic, Peduzzi said he sees plenty of need for the center and what it does.
“We are still building and growing,” he said.