INCE ITS FOUNDING, UNC’s school of public health S has encouraged innovators who developed new ways of collecting and analyzing information and solving problems. At the heart of that effort has been a synergistic collaboration of the School’s basic measurement science departments—biostatistics, epidemiology, and environmental sciences and engineering—along with other departments that have strong methods and measurement science foci. These include the School’s departments of health policy and management, health behavior, maternal and child health, and nutrition, as well as others outside the School. DATA DRIVEN BY CARING AND CHANGE 48 | CAROLINA PUBLIC HEALTH DATA DRIVEN BY CARING IF YOU ALWAYS DO WHAT YOU’VE ALWAYS DONE, YOU’LL ALWAYS AND GET WHAT YOU’VE ALWAYS GOT. CHANGE —HENRY FORD FALL 2014 | 49 [Above, left to right]: Drs. Jim Grizzle, Bernard Greenberg, Dale Williams and Michel Ibrahim discuss plans for renewal of their research grant on lipids; Drs. Gary Koch and Dennis Gillings conducted clinical trials work from a trailer on School grounds; Dr. Gillings, as a faculty member in 1971. DEVELOPMENT mathematical statistics department at drugs. Under Greenberg’s leadership, UNC-Chapel Hill. In 1949, less than the department developed a roadmap OF BIOSTATISTICS a decade after the School began, she for evaluating new drugs for efficacy. helped establish the Department of Without the clinical trials methodol- METHODS Biostatistics in the UNC–Chapel Hill ogy and infrastructure developed by School of Public Health, selecting her UNC’s biostatisticians, many advances former student, Bernard Greenberg, that benefit individuals might nev- In 1940, UNC system president Frank PhD, to lead it. er have been made. Members of the Porter Graham took a chance in hiring Greenberg, who later became the biostatistics faculty continue to make Gertrude Cox, MS, as the first woman department’s first Kenan Distinguished innovations in clinical trials. professor and department head at Professor, was awarded a National In 1967, NIH’s National Heart N.C. State University. Cox, professor of Institute of General Medical Sciences Institute commissioned Greenberg statistics and head of the Department grant, “Multivariate Analysis for the to develop procedures for conducting of Experimental Statistics, likely met Health Sciences,” with co-principal large, multicenter clinical trials. His Graham’s highest expectations; her investigator S.N. Roy, MSc. With Greenberg Report (see tinyurl.com/ hiring certainly set in motion a series of support from Hotelling and others Greenberg-report) is still a respected events that resulted in one of the finest in the UNC–Chapel Hill statistics document, having established methods biostatistics departments in the world. department, Greenberg also competed to evaluate new drugs and cancer As the UNC system’s graduate successfully for one of the first National treatments that have been used for program in statistics was housed at Institutes of Health (NIH) grants to nearly 50 years. N.C. State, it was incumbent upon Cox train biostatisticians and pioneered The tradition of statistical to develop any additional statistics efforts to establish the practice of innovation for the betterment of programs on other campuses. In 1946, cooperative multicenter trials. humankind continues in a program led she recruited Harold Hotelling, PhD, This groundbreaking, transforma- today by Michael Kosorok, PhD, W.R. formerly on the faculties of Stanford tional research changed the course Kenan Jr. Distinguished Professor and Columbia, to head the new of practice for the evaluation of new and chair of biostatistics, who 50 | CAROLINA PUBLIC HEALTH collaborates with colleagues at UNC, continuously funded NIH coordinating “With that,” Grizzle says, Duke and N.C. State universities, and center in the U.S., having coordinated “biostatisticians changed the world.” SAS (SAS.com), a business analytics studies with hundreds of clinical centers Williams, who succeeded Grizzle software and services company. in the U.S. and abroad. The late H.A. as principal investigator for the study, The National Cancer Institute Tyroler, MD, Alumni Distinguished says that trial “set the stage for the drug (NCI)-funded program, “Statistical Professor of epidemiology, was a vital development that led to statins and Methods for Cancer Clinical Trials,” is contributor to the study group and lipid-lowering compounds.” pioneering new methods that will help provided much insight into the tools Grizzle’s methodology for crossover researchers more effectively discover and methods used by the CSCC. Grizzle, trials is still referred to today, some 50 and evaluate cancer treatments, as well Clarence (Ed) Davis, PhD, retired years later. Another paper by Grizzle, on as treatments for other diseases, and former chair of biostatistics and director analyzing categorical data and whose to more quickly deliver effective new of the CSCC, and Dale O. Williams, co-authors included Frank Starmer, therapies to patients. PhD, took the lead in the first study, PhD, now with the Duke University- The biostatistics department was which found that lowering cholesterol National University of Singapore successful from the start in attracting reduces the risk of heart disease. Graduate Medical School, and financial support through contracts biostatistics professor Gary Koch, PhD, and grants, says Jim Grizzle, PhD, is among the most-cited biostatistics who chaired the department from papers in the world. 1972 to 1987. In 1958, Greenberg undertook In 1955, the NCI awarded the another landmark epidemiological department a contract to become the study—the first large study of statistical coordinating center for the cardiovascular disease that included Southeastern Cooperative Cancer African-Americans. All other large Chemotherapy Study Group (SCCC), trials in the U.S. at the time had only believed to be the first large-scale white participants. The Evans County, clinical trials group in the U.S. (The first Ga., study continued through the such study was published in England 1990s. (See tinyurl.com/evans-county.) in 1949.) Faculty members from 10 “All of these studies had a real medical schools and the coordinating impact on the health of society,” says center collaborated to investigate the Ed Davis. The studies led to insights effectiveness of chemotherapy agents. and treatment options for widespread The department developed some of health problems, such as high the new mathematics necessary to an- cholesterol and congestive heart failure. alyze data from these large-scale, mul- The impact continues with research ticenter trials. In 1957, Greenberg hired in progress now, including the Hispanic Grizzle as a graduate research assistant. Dr. Gary Koch, in the 1980s, stands Grizzle led the Lipid Research Clinics outside his office in ‘Trailer 39.’ Coordinating Center, established in 1971, which was among the first groups to perform distributive data entry. The unit was renamed the Collaborative Studies Coordinating Center (CSCC) in 1986, and is now the oldest, FALL 2014 | 51 Community Health Study/Study of and Drug Administration, both for- the CSCC in 1991, had cumulative Latinos, the largest, long-range study mer biostatistics professors and CSCC oversight of $35 million in grants. to date on this population. An original directors, and is currently overseen by UNC’s School of Public Health $22 million grant from the National Jianwen Cai, PhD, professor and vice extended its international reach, Heart, Lung and Blood Institute chair of biostatistics. Twelve faculty particularly in the 1960s after supported the multi-center study of members, 24 staff members and four Pranab K. Sen, PhD, DSc, Cary C. more than 16,000 Hispanic adults to students from UNC are involved in Boshamer Distinguished Professor, examine the role of acculturation in the study. joined the faculty and strengthened the prevalence of disease. A six-year, Grant funding reflected the ties to universities in India. Sen $21.7 million federal contract was biostatistics department’s success. has contributed significantly to also awarded to conduct a second Grizzle recalled that his department’s methodological studies related to examination of study participants, budget hovered close to $6 million diabetes, environmental health and beginning in October 2014. annually, but the state contributed bioinformatics, as well as clinical trials. The study was initiated by Lloyd only $90,000. The rest came from The lipids study also fostered a Chambless, PhD, now retired, and Lisa grants and contracts. Dale Williams, stream of global interactions, including LaVange, PhD, now at the U.S. Food who succeeded Grizzle as director of ones with eastern European countries, SPEEDING UP DRUG DEVELOPMENT, IMPROVING CLINICAL TRIALS Data pile up fast in large-scale, long-term, multisite clinical trials. As data collection methods evolve, so too must the means by which data are analyzed. Early on, the Gillings School’s biostatistics department developed a reputation for its program in Bayesian statistics, an analysis paradigm that involves determining probability of something based on particular pieces of evidence. The program is led by Alumni Distinguished Professor Joseph G. Ibrahim, PhD, who also directs the UNC Center for Innovative Clinical Trials (CICT) and the department’s graduate studies program. Ibrahim and colleagues in the CICT have conducted leading- edge research on innovative Bayesian clinical trials design, including development of new statistical