of finding new uses for existing drugs. Photo: Pixabay
Scientists have developed a machine-learning method that
crunches massive amounts of data to help determine which existing
medications could improve outcomes in diseases for which they are
The intent of this work is to speed up drug repurposing, which
is not a new concept â think Botox injections, first approved to
treat crossed eyes and now a migraine treatment and top cosmetic
strategy to reduce the appearance of wrinkles.
But getting to those new uses typically involves a mix of
serendipity and time-consuming and expensive randomized clinical
trials to ensure that a drug deemed effective for one disorder will
be useful as a treatment for something else.
The Ohio State University researchers created a framework that
combines enormous patient care-related datasets with high-powered
computation to arrive at repurposed drug candidates and the
estimated effects of those existing medications on a defined set of
Though this study focused on proposed repurposing of drugs to
prevent heart failure and stroke in patients with coronary artery
disease, the framework is flexible â and could be applied to most
âThis work shows how artificial intelligence can be used to
âtestâ a drug on a patient, and speed up hypothesis generation
and potentially speed up a clinical trial,â said senior
Zhang, assistant professor of computer science and
engineering and biomedical
informatics at Ohio State. âBut we will never replace the
physician â drug decisions will always be made by
The research is published today (Jan. 4, 2021) in Nature Machine
Drug repurposing is an attractive pursuit because it could lower
the risk associated with safety testing of new medications and
dramatically reduce the time it takes to get a drug into the
marketplace for clinical use.
Randomized clinical trials are the gold standard for determining
a drugâs effectiveness against a disease, but Zhang noted that
machine learning can account for hundreds â or thousands â of
human differences within a large population that could influence
how medicine works in the body. These factors, or confounders,
ranging from age, sex and race to disease severity and the presence
of other illnesses, function as parameters in the deep learning
computer algorithm on which the framework is based.
That information comes from âreal-world evidence,â which is
longitudinal observational data about millions of patients captured
by electronic medical records or insurance claims and prescription
âReal-world data has so many confounders. This is the reason
we have to introduce the deep learning algorithm, which can handle
multiple parameters,â said Zhang, who leads the Artificial
Intelligence in Medicine Lab and is a core faculty member in
the Translational Data Analytics
Institute at Ohio State. âIf we have hundreds or thousands of
confounders, no human being can work with that. So we have to use
artificial intelligence to solve the problem.
âWe are the first team to introduce use of the deep learning
algorithm to handle the real-world data, control for multiple
confounders, and emulate clinical trials.â
The research team used insurance claims data on nearly 1.2
million heart-disease patients, which provided information on their
assigned treatment, disease outcomes and various values for
potential confounders. The deep learning algorithm also has the
power to take into account the passage of time in each patientâs
experience â for every visit, prescription and diagnostic test.
The model input for drugs is based on their active ingredients.
Applying what is called causal inference theory, the researchers
categorized, for the purposes of this analysis, the active drug and
placebo patient groups that would be found in a clinical trial. The
model tracked patients for two years â and compared their disease
status at that end point to whether or not they took medications,
which drugs they took and when they started the regimen.
âWith causal inference, we can address the problem of having
multiple treatments. We donât answer whether drug A or drug B
works for this disease or not, but figure out which treatment will
have the better performance,â Zhang said.
Their hypothesis: that the model would identify drugs that could
lower the risk for heart failure and stroke in coronary artery
The model yielded nine drugs considered likely to provide those
therapeutic benefits, three of which are currently in use â
meaning the analysis identified six candidates for drug
repurposing. Among other findings, the analysis suggested that a
diabetes medication, metformin, and escitalopram, used to treat
depression and anxiety, could lower risk for heart failure and
stroke in the model patient population. As it turns out, both of
those drugs are currently being tested for their effectiveness
against heart disease.
Zhang stressed that what the team found in this case study is
less important than how they got there.
âMy motivation is applying this, along with other experts, to
find drugs for diseases without any current treatment. This is very
flexible, and we can adjust case-by-case,â he said. âThe
general model could be applied to any disease if you can define the
The research was supported by the National Center for Advancing
Translational Sciences, which funds the Center for Clinical and Translational
Science at Ohio State.