GW Biostatistics Center Marks 50 Years of Transformational Research

By Kristen Mitchell

This spring, the George Washington University Biostatistics Center is celebrating 50 years of groundbreaking research that has improved the health outcomes and quality of life for millions of people worldwide. The center’s large-scale public health and medical studies, conducted in close partnership with scientists and clinical sites across the United States and internationally, have transformed our understanding and treatment of everything from diabetes complications such as blindness and kidney failure to birth disorders like cerebral palsy.

Biostatistics applies statistical methods to the design, conduct, analyses, interpretation and reporting of research studies that address important research questions in public health and medicine. Such research results in evidence-based strategies to diagnose, prevent and treat diseases. As a national leader in clinical trials and biostatistics methodology research, the center aims to improve public health and clinical practice by conducting transformative scientific research, with a focus on providing leadership and expertise in the execution of clinical trials, observational studies and diagnostic studies.

 

 

 

 

 

Over the past five decades, the center has done just that, having published more than 1,700 papers, including 61 in the New England Journal of Medicine, and been cited countless times in reports to the United States president and Congress. In addition, the center has advanced biostatistical science by developing and implementing innovative approaches for the design, conduct, analysis and reporting of clinical research studies. It provides training and education to GW students relevant to clinical trials and other clinical research, currently employing 20 students.

Scott Evans, director of the Biostatistics Center, and professor and founding chair of the Milken Institute School of Public Health Department of Biostatistics and Bioinformatics, described the center’s role as the nucleus of a much broader research endeavor.

"We hope to have a positive impact on public health and medicine through leading research projects that inform how you diagnose, treat or prevent diseases in patients,” he said. "What is most rewarding to see is the enormous magnitude of the impact that our studies have in the lives of patients, and the role that the center has had in the lives of the people that have worked there."

A Mighty Enterprise

Founded in 1972 as part of the Department of Statistics, the center moved to the Office of the Vice Provost for Research in 2002 before moving to the Milken Institute SPH in 2016, where it is housed today.

Located in Rockville, Maryland, the center is close to the National Institutes of Health (NIH), which has funded 99% of the center’s research. The center’s research contributions align closely with NIH priorities for advancement in health and medicine. It has worked particularly closely with the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), among the largest of the NIH’s 27 institutes.

"The center has helped coordinate and analyze the results of some of the most consequential studies the National Institute of Diabetes and Digestive and Kidney Diseases has funded, leading to widespread improvements in prevention, treatment and outcomes for people with diabetes and many other conditions in NIDDK’s mission,” said Griffin P. Rodgers, director of the NIDDK. “Their contributions and leadership have been invaluable, and I congratulate them on 50 years of outstanding work."

The center had nearly $58 million in research expenditures in fiscal year 2021. Its research activities support more than 100 employees and serve as a strong training ground for GW students including doctoral and master’s degree students.

Katrina Billingsley has worked at the center for 30 years, where as director of administration her team oversees the roughly 200 active subawards on the center’s current projects. The rewarding feeling of knowing you are making a difference is what has kept the center’s long-time staff engaged and motivated over the years, she said.

“When you stop and think about these great things that are happening as a result of everyone working, it really is amazing,” she said.

Lynn R. Goldman, the Michael and Lori Milken Dean of the Milken Institute SPH, applauded the center’s “impressive track record of leading, coordinating and managing ground-breaking clinical trials and large long-term cohort studies that have changed the way we prevent and treat diseases from preterm birth to diabetes to COVID.

“Now, in its 50th year, the Biostatistics Center continues to provide leadership on new research aimed at improving public health and saving lives,” she said.

Groundbreaking research in diabetes

More than 37 million Americans are living with diabetes, according to the Centers for Disease Control and Prevention (CDC). Over the past several decades, the center has led multiple studies that have had an “enormous impact” in the treatment, management, and prevention of diabetes, Evans said.

 

 

 

 

 

 

 

 

 

In the 1980s, GW researchers led the Diabetes Control and Complications Trial (DCCT) involving 28 clinical centers to test the glucose hypothesis—a theory that elevated blood glucose associated with diabetes was responsible for the development and progression of complications that caused blindness, kidney disease and amputation. The study established glycemia as a major risk factor and mechanism for the onset of Type 1 diabetes complications—setting a new worldwide standard for Type 1 diabetes care. The Harvard Health Letter named the DCCT the most significant advancement in medicine in 1993.

The DCCT study led to therapeutic interventions that drastically reduced diabetes-related blindness, renal failure and amputation, and its primary publication has been cited more than 22,000 times. Moreover, the center continues to follow the DCCT cohort through the Epidemiology of Diabetes Interventions and Complications study to better understand the long-term effects of diabetes treatment.

Research professor John Lachin has been working with the center since 1973, serving as director from 1988 to 2000 and 2010 to 2012. As an expert in biostatistics, he contributed to many of the center’s landmark studies.

“The DCCT was the most important thing I'll ever do,” he said. “The fact that the NIH and GW had the confidence in me to be able to play that role is immensely gratifying.”

The center also led the Diabetes Prevention Program (DPP), a major clinical research study that found lifestyle interventions reduced the risk of developing Type 2 diabetes by more than half over three years, particularly for those under age 60. That program was adopted by the CDC and led to the formation of a national program to ​​address prediabetes and Type 2 diabetes in the United States. Like with the DCCT study, GW continues to follow up with the DPP cohort to evaluate the effects on long-term development of diabetes and associated complications. The DPP Study Group is planning to study Alzheimer’s disease and Alzheimer’s disease related dementia in prediabetes and Type 2 diabetes in the DPP cohort. 

Center researchers are currently working on a clinical study focused on medications to control blood glucose levels, the Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness Study (GRADE). Most people with diabetes eventually need two medications to control blood glucose levels, however, it’s unknown which two-drug combination is best. Researchers have been collecting data from 5,000 patients already treated with the most commonly used diabetes drug to answer this question, a seven-year undertaking involving 40 clinical sites. The study results will be published this year.

“We expect that the results of the GRADE study will define diabetes treatment for the next generation,” Evans said.

David Nathan, director of the Diabetes Clinical Research Center at Massachusetts General Hospital and professor at Harvard Medical School, has collaborated with the Biostatistics Center for 40 years on landmark studies including the DCCT, DPP and GRADE. Working with the center has been “endlessly rewarding,” he said.

"Being a coordinating center for one of these studies is highly complicated, and there are only a few centers in the country who do it anywhere near the level that GW does,” he said. “Big answers in medicine and science come out of these kinds of studies and being able to support them as the Biostatistics Center has in the past and continues to do, is incredibly important."

Better health outcomes for mothers and infants

Since 1986, the center has led the scientific and operational coordination of the Maternal Fetal Medicine Units (MFMU) that focuses on clinical questions in maternal-fetal medicine and obstetrics. The MFMU aims to reduce the rates of preterm birth, fetal growth abnormalities, newborn morbidity and maternal complications of pregnancy. It also evaluates maternal and fetal interventions to determine if they are effective and safe.

 

 

 

The MFMU has taken on 33 randomized trials and 26 observational studies since its founding and published more than 380 manuscripts. Many of the center’s studies in this area have defined procedures done during pregnancy to either prevent various complications or optimize outcomes for mothers and infants.

The MFMU works with 32 clinical sites, enabling data collection on 160,000 deliveries per year—4% of annual births in the United States. This racially, ethnically and geographically diverse data allows study results to be generalizable to the country’s population.

In 2008, one of MFMU clinical trials, the Beneficial Effects of Antenatal Magnesium Sulfate (BEAM) trial showed the babies of women who were given magnesium sulfate while pregnant, had significant reduction in moderate to severe cerebral palsy. As a result, the American College of Obstetricians and Gynecologists and the Society for Maternal Fetal Medicine Committee on obstetric practice recommended that magnesium sulfate be given before anticipated early preterm birth. It is now routinely given to pregnant individuals.

The MFMU also conducted the Management of Myelomeningocele (MOMs) clinical trial which compared prenatal vs. postnatal correction of myelomeningocele, the most common and serious form of spina bifida, a spinal birth defect. The study found that prenatal surgery could improve outcomes, a procedure that is now available at several medical centers across the country today.

“The MFMU Network has produced the most studies with the highest impact on outcomes of pregnancy,” said George Saade, chief of obstetrics and maternal fetal medicine at the University of Texas Medical Branch. “The studies have introduced new practices or stopped unnecessary practices, all to the benefit of mothers and their children. Without any doubt, maternal mortality and morbidity rate would be much higher if there was no MFMU Network.” 

Currently the MFMU is conducting a study associated with the NIH’s Helping to End Addiction Long-term (HEAL) initiative to address the opioid crisis. The Center leads the ongoing Opioid Prescription After Cesarean Trial (PACT), comparing an individualized opioid prescription protocol that includes shared decision making to a fixed opioid prescription in pain management, with respect to maternal and infant outcomes.

According to Evans, the MFMU owes much of its success to the leadership and vision of past and current investigators, including Elizabeth Thom, a research professor who died earlier this year at age 72.

 

 

 

“Professor Thom was a giant in the field,” he said. “She was internationally recognized as the pre-eminent biostatistician in maternal-fetal medicine, a distinguished researcher who contributed in immeasurable ways to the improvement of obstetric and perinatal care, and to fetal diagnosis and therapy.”

During her time as a principal investigator of the MFMU, Thom brought in nearly $200 million in research funding to GW and employed over 180 people on her research projects throughout the years.

“The lives of countless mothers and babies are much better because of Thom’s work and influence,” said Saade. “Thom was the foundation and engine of the MFMU Network. I cannot think of any other person who had more impact on obstetrical care than Thom, directly through her work in the MFMU Network and other trials, as well as indirectly through training of hundreds of researchers. Her impact will continue to resonate for generations.”

Thom’s legacy and work is being continued by the MFMU’s current principal investigator, Rebecca Clifton, associate research professor of epidemiology.

Fighting viruses and bacteria

In addition to its landmark studies in diabetes and maternal-fetal medicine, the center is helping address other health crises that have gained public attention in the last decade. When it became clear in spring 2020 that the SARS-CoV-2 virus was going to have an enormous impact on society, the center was galvanized, Evans said.

“We were motivated to contribute in any way that we could,” he said.

 

 

In the early months of the COVID-19 pandemic, the center launched three projects to design, conduct, analyze and report COVID-19 studies. Housed under the COVID-19 Community Research Partnership, the first project, funded by the State of North Carolina, aims to learn more about COVID-19 by studying patients in five health care systems throughout the state.

GW serves as the data coordinating center for the project and works with investigators at the Wake Forest School of Medicine. The second project, funded by the CDC, is an expansion of the surveys to multiple states, including Maryland, Louisiana and Mississippi. The cohort now has more than 60,000 patients.

In a third project, funded by the NIH, the center joined with researchers across the country to better understand how COVID-19 affects pregnancy outcomes. Findings from that study uncovered that pregnant people who experienced severe symptoms of COVID-19 had a higher risk of complications during and after pregnancy compared to asymptomatic COVID-19 patients.

The center is also engaged in other infectious disease research such as antibiotic-resistant bacteria “superbug” infections—one of the most serious health threats to global health. According to the CDC, more than 2.8 million people in the United States acquire serious bacterial infections that are resistant to antibiotics designed to treat those infections annually, resulting in at least 35,000 deaths. According to the Interagency Coordination Group on Antimicrobial Resistance, drug-resistant diseases already cause at least 700,000 deaths globally per year.

Antibiotic resistance also threatens the safety and effectiveness of many medical treatments and procedures that rely on having effective antibiotics such as chemotherapy for cancer, dialysis for renal failure, neonate care, and surgeries such as organ transplantation.

A deadly superbug outbreak at the NIH Clinical Center in 2011 led to the formation of the Antibacterial Resistance Leadership Group (ARLG), a collaborative clinical research network that would prioritize, design and execute clinical research to reduce the public health threat of antibacterial resistance. Evans serves as director of the statistical and data management center of the ARLG, which is conducting several clinical trials, observational studies and diagnostics studies.

Principal investigator of the ARLG Henry “Chip” Chambers, III, a professor of medicine and chief of the division of infectious diseases at San Francisco General Hospital, said the methodological contributions in biostatistics have been among the most important and impactful contributions to the ARLG.

“The methods developed by Evans and his team are transforming how we think about the design and analyses of clinical trials,” Chambers said. “We are able to gain a much deeper understanding of the effects of interventions on patients, resulting in better research studies and ultimately more-informed patient care in the setting of antibiotic resistance.”

Future research

The center is diversifying its focus on new disease areas and the types of studies it executes in the years to come, Evans said, while also continuing to advance research in historical strength areas. It is doing this by fostering strong relationships with GW colleagues across various schools, centers, laboratories and disciplines, and creating new collaborations with external partners.

“We've made a lot of progress in a number of different disease areas,” he said. “We want to continue to build upon that success.”

One example is a recent collaboration with the Milken Institute SPH department of exercise and nutrition sciences on an award from the National Cancer Institute to establish the Coordinating Center for the Exercise and Nutrition Interventions to Improve Cancer Treatment-Related Outcomes in Cancer Survivors Consortium. The consortium will conduct research on exercise and medical nutrition interventions designed to improve cancer treatment-related outcomes. Evans and Kim Robien, associate professor at Milken Institute SPH, will serve as the principal investigators.

The center’s researchers are currently developing initiatives focused on cardiovascular disease, Evans said, the leading cause of death in the United States. The expansion of the DPP study to Alzheimer's disease may open the door to more research opportunities to this top NIH priority. The center will be able to expand its scope of work as new faculty are brought on board.

Evans is also interested in pursuing new types of studies that harness advancements in electronic medical records, as was done in the center’s COVID-19 research. Technology advancements change the type of data available for analysis.

“We're trying to evolve to take full advantage of the rapid growth in technologies, availability of different types of data that are available for study, and the changing regulations,” Evans said.

Lachin, the researcher and former center director, said he’s watched as the university has become more focused on its role as a major research institution over the past 50 years.

“We've contributed greatly as a research center to support that growth,” he said. “I hope the center continues to grow.”