Research Effort Aims to Bring Personalized Medicine to Drug Prescriptions

A Columbia University-led multicenter research effort called IndiPHARM: individual metabolome and exposome assessment for pharmaceutical optimization will develop a platform and monitoring system to prevent unwanted interactions between medications and other environmental, genetic, and lifestyle factors, in order to optimize therapeutic efficacy. IndiPHARM is supported by $39.5 million in funding from the Advanced Research Projects Agency for Health (ARPA-H), a federal research funding agency that supports transformative biomedical and health breakthroughs.

The IndiPHARM platform will be designed to measure hundreds of drugs and their metabolites and thousands of chemicals derived from the environment, diet, and lifestyles. Ultimately, the goal is to optimize how medications work by equipping individuals and their doctors with a tool that can answer the question, “Is the drug or combination of drugs I am taking optimized for me?” The platform will also help pharmaceutical suppliers, insurance payors, and providers to anticipate and reduce adverse therapeutic effects, including side effects and inefficiencies, in both individuals and populations.

“This project exemplifies how cutting-edge technologies and scientific collaborations across institutions and sectors can promote human progress and reduce suffering. IndiPHARM promises nothing less than to revolutionize pharmacology and patient care,” says Katrina Armstrong, MD, Interim President, Columbia University, and Chief Executive Officer, Columbia University Irving Medical Center.

Led by Gary Miller, PhD, Vice Dean for Research Strategy and Innovation and Professor of Environmental Health Sciences, at Columbia University Mailman School of Public Health, IndiPHARM also includes investigators from the Mayo Clinic, Harvard Medical School, Emory University, Brown University, and the Jackson Laboratory. The five-year ARPA-H agreement aims to catalyze a commercial venture.

“Medications have the potential to reduce suffering, alleviate symptoms, prevent serious events, and help people live longer and healthier lives. Unfortunately, there is a gap between what drugs are predicted to do and what they actually do in the real world,” says Miller, a globally recognized authority on the exposome. “IndiPHARM is marshaling the technology to bridge this gap.”

Doctors have more than 10,000 prescription drugs in their armamentarium, yet they lack basic information about how these drugs interact with each other and with an individual patient’s biology. Too often doctors and patients must resort to a costly, time-consuming, and sometimes dangerous process of trial and error to find the right medication or medication mixture, at the right dosage. According to the Agency for Healthcare Research and Quality, each year, adverse drug events (ADEs) account for nearly 700,000 emergency department visits and 100,000 hospitalizations.

Why do prescription drugs affect people differently? Individual differences in genetic composition explain only a small fraction of the variability. This suggests that non-genetic factors explain the varied and often suboptimal performance of medications. The field of exposomics, which is focused on measuring the physical, chemical, biological, and psychosocial influences that impact health, has matured to a point where it can help identify the varied factors that impede the effectiveness of a drug or combination of drugs. Miller notes, “As our teams developed the analytical methods for exposomics, we recognized that not only did we have the tools to measure thousands of environmental factors but also thousands of drugs and their metabolites, and that we could do it all at the same time.”

(In related news, this week, the National Institute of Environmental Health Sciences created a new national exposomics coordinating center led by Gary Miller.)  

The APRA-H funding will accelerate these efforts, which include extracting data from electronic health records, obtaining blood samples from well-characterized patients, automating sample prep, optimizing mass spectrometry protocols, streamlining data extraction and bioinformatics, and getting the tools into the clinic. The goal is to identify and prioritize drugs, drug classes, and exposure patterns that can be used to adjust or improve therapies.

By developing tests that can be used across dozens of health conditions, it should be possible to identify situations that interfere with drug therapy and adjust if needed. Are you a fast metabolizer of one of your medications? Are you taking the right dose? How do these drugs interact? Does your diet impact how your mediations work? Are the supplements you are taking interfering with your medications? Are the chemicals you are exposed to at work or in your neighborhood having an impact on your treatment? IndiPHARM will develop and validate a series of rapid, cost-effective tests that will make it possible to answer these questions.

The IndiPHARM team will start by focusing on metabolic conditions such as obesity, pre-diabetes, diabetes, fatty liver disease, and the common conditions that co-occur, including hypertension, high cholesterol, and depression. However, the platform could be used for nearly all human diseases and drug classes. The researchers will start by analyzing data from the LookAHEAD and ACCORD diabetes trials, the Tapestry study at Mayo Clinic, alongside electronic health records from the OHDSI database to identify relationships between drug therapy and treatment outcomes, as well as the complex physiologic states linked to sub-optimal therapy outcomes. Further ahead, they will apply their learnings to develop a test to predict drug efficacy and minimize adverse events.

The IndiPHARM team includes Columbia University (Miller, Randolph Singh, PhD, Serge Cremers, PhD, George Hripcsak, MD); Harvard Medical School (Chirag Patel, PhD); Mayo Clinic (Konstantinos Lazaridis, MD, Arjun Athreya, PhD); Emory University (Doug Walker, PhD, Xin Hu, PhD, Dean Jones, PhD, Young-Mi Go, PhD); Brown University (Kurt Pennell, PhD); Jackson Laboratory (Shuzhao Li, PhD). Members of the team have been working together for over a decade with over 100 collaborative papers and multiple collaborative NIH grants.

The IndiPHARM team has a multifaceted strategy to commercialize the technology generated under the project. Consulting advisors and partners include Columbia Tech Ventures, AlleyCorp, Thermo Fisher, MBX Capital, Amazon Web Services, and others. IndiPHARM is funded through the ARPA-H Health Science Futures Office.