Department of Statistics
Presents the
Robert W. Makuch Distinguished Lecture in Biostatistics
Featuring
Lee-Jen Wei
Professor of Biostatistics
Harvard University
Lost in Translation
abstract
Over the years, the process of designing, monitoring, and analyzing clinical studies for evaluating new treatments has gradually fallen into a fixed pattern. Clinical trialists have sometimes been slow to utilize new methodologies–perhaps to avoid potential delays in the review process for drug approval or manuscript submission. The underlying attitude toward innovation in drug development is in sharp contrast to that in other technologically-driven fields. Scientific investigation is an evolving process. What we have learned from previous studies about methodological shortcomings should help us better plan and analyze future trials. Unfortunately, use of inefficient or inappropriate procedures persists even when better alternatives are available. In this talk, we will explore various methodological issues and potential solutions to them. A goal of the clinical study is to obtain robust, clinically interpretable treatment effect estimate with respect to risk-benefit perspectives at the patient’s level via efficient and reliable quantitative procedures. We will discuss how to achieve this goal via various real trial examples. This talk is related to the so-called “translational statistics and data science.”
DATE: Friday, April 14, 2023
TIME: 12:00 pm-1:00 pm EST
Location: AUST 434
WebEx Address: https://uconn-cmr.webex.com/uconn-cmr/j.php?MTID=mf12a26e8ee595beaa1510a7e2d23af3f
Coffee will be served at 11:30 am in AUST 326
L.J. Wei's research is in the area of developing statistical methods for the design and analysis of clinical trials. In 1977-78 he introduced the "urn design" for two-arm sequential clinical studies. This design has been utilized in several large-scaled multi-center trials, for example, the Diabetes Control and Complications Trial sponsored by the NIH and the Matching patients to Alcoholism Treatments sponsored by NIAAA.
In 1979, he proposed a response adaptive design, a randomized version of Marvin Zelen's play the winner rule, was used in the ECMO trial, a well-known study which evaluated extracorporeal membrane oxygenation for treating newborns with persistent pulmonary hypertension. Currently several trials sponsored by private industry are using this particular design to relax the ethical problem arising in using the conventional 50-50 randomization treatment allocation rule clinical studies. To monitor trials sequentially for economic and ethical reasons, in 1982 Wei and his colleagues presented a rather flexible monitoring scheme, which has become a classical reference for the literature in interim analysis for clinical trials.
Dr. Wei has developed numerous methods for analyzing data with multiple outcome or repeated measurements obtained from study subjects. In particular, his "multivariate Cox procedures" to handle multiple event times have become quite popular. He and his colleagues are also responsible for developing alternative models to the Cox proportional hazards model for analyzing survival observations.
A very important issue in statistical inference is to check whether the model used to fit the data is appropriate or not. Currently, Wei and his colleagues are developing graphical and numerical methods for checking the adequacy of the Cox proportional hazards model, other semi-parametric survival models, parametric models, and random effects models for repeated measurements. The new procedures are much less subjective than the conventional eye-ball methods based on ordinary residuals plots.
Since the cost of computing has been drastically reduced, some analytically intractable statistical problems can be handled numerically. Presently, Wei and his colleagues are working on various resampling methods for quantile regression, rank regression, and regression models for censored data.
Dr. Wei is also a senior statistician at the Statistical and Data Analysis Center. He works closely with the medical investigators in Pediatrics AIDS clinical trials for evaluating new treatments for HIV patients.
Robert Makuch is a Professor in the Department of Biostatistics at the Yale School of Public Health and Director of the Regulatory Affairs Track. A graduate of the University of Connecticut (BA), University of Washington (MA – mathematics), and Yale University (MPhil, PhD), Professor Makuch worked at the National Cancer Institute (NCI) and the World Health Organization’s International Agency for Research on Cancer early in his career. He also worked for six months at the National Cancer Research Center in Tokyo, Japan.
He also was heavily involved in HIV research from the mid 80's through the early-mid 90's. He participated on the data monitoring committee for the original AZT vs. placebo randomized clinical trial in AIDS patients, and served on numerous committees for the NCI and the National Institute of Allergy and Infectious Diseases. He also worked closely with the Food and Drug Administration (FDA), developing and implementing more than 200 HIV studies. He also served as a Special Government Employee (SGE) to the FDA. He returned to Yale in 1986, and has worked extensively on methodologic issues in clinical trials and large population-based studies since. Another area of current interest involves detection of rare adverse drug events, especially in the post-marketing environment.
These areas of methodologic research evolved as a result of his continued interest (since the mid 1980s) in regulatory affairs science. In addition, Makuch developed a regulatory affairs track at YSPH for graduate and post-doctoral level students, and over the past 10 years has been the leader of more than 25 training programs for senior delegations of the Chinese Food and Drug Administration. His areas of medical application include cancer, HIV, arthritis, and cardiovascular disease.
In 2003, Makuch received the American Statistical Association Fellow Award for his numerous contributions to the field. In 2008, Makuch was received a Distinguished Alumni Award from the University of Connecticut. In 2012, Makuch was nominated to serve on the University of Connecticut Dean's Advisory Board for the College of Liberal Arts and Sciences. He also has been a decades-long member of Phi Beta Kappa. He also developed a 5-year biostatistics training program in Japan, in collaboration with the Japanese government. His primary research interests continue to be methodologic issues in the design, conduct, analysis, and interpretation of clinical and large-population/epidemiologic studies. Design and sample size considerations for Phase IV studies is another active research area, in which a new class of hybrid designs has been proposed for scientific and regulatory purposes to detect rare adverse events.
For more information, contact: Tracy Burke at tracy.burke@uconn.edu