PROJECT SUMMARY/ABSTRACT
The objective of this K01 award is to provide Dr. Joshua Wallach, an Assistant Professor of Epidemiology at
the Yale School of Public Health, with the protected time necessary to become an independent expert in
synthesizing, evaluating, and establishing the best evidence to inform clinical practice in the field of alcohol use
disorder (AUD). Although AUD is a common and morbid disease, for which medication treatment is available,
uncertainties about whether and for whom treatments work may be causing AUD medication underutilization.
To advance the evidence base to support AUD medication treatment, research is needed to identify patient
subgroups that are most likely to benefit from each medication used to treat AUD. However, traditional
subgroup analyses often consider only one patient characteristic at a time and are conducted in small clinical
trials with strict exclusion criteria, short durations, and outcomes that may not reflect how patients feel or
function. This proposed K01 will address these limitations by conducting subgroup analyses using multiple
data sources, outcomes, and analytical techniques. In Aim 1, Dr. Wallach will identify and assess the validity of
already published subgroup analyses to establish promising patient subgroups that are most likely to benefit
from each medication used to treat AUD. In Aim 2, existing data from the largest AUD trial in the US (the
COMBINE study) will be used to (a) corroborate promising patient subgroup differences identified in Aim 1 and
(b) explore new differences between patient subgroups, using multiple methods (i.e. traditional and statistical
learning, which can consider multiple characteristics) and outcome measures (abstinence, heavy drinking, and
2-shift reduction in World Health Organization drinking levels). In Aim 3, claims data from OptumLabs, a
database of over 150 million privately insured and Medicare Advantage enrollees, will be used to determine
whether the same, similar, or new differences between patient subgroups are observed in real-world settings
when hospital and ambulatory care outcomes are considered. These aims will clarify uncertainties among
patients and clinicians regarding the adoption of AUD medications, which can decrease the public health
burden associated with AUD. To support these aims, Dr. Wallach’s career development plan will include
training in: (1) AUD medications and addiction medicine, (2) novel statistical learning techniques that can be
used to inform individualized clinical decision making, and (3) pharmacoepidemiology and observational
research methods for real-world medical product evaluation. The candidate has identified an interdisciplinary
team of mentors and advisors, including co-primary mentors Dr. Joseph Ross, a health services researcher
and administrative data expert, and Dr. Stephanie O’Malley, an AUD treatment and addiction medicine expert.
The Yale Schools of Public Health and Medicine provide the ideal environment for career development. This
K01 will prepare Dr. Wallach for an R01 submission, and will facilitate his long-term goal of developing an
innovative research program combining meta-research and real-world evaluation to improve AUD clinical care.