COVID-19 treatment study predicts adverse drug events

One of the many challenges around discovering effective treatments for the COVID-19 virus centers around determining how treatments might impact current medication regimens. Researchers with Tabula Rasa Healthcare (TRHC) have tackled the issue with a novel simulation study that breaks down the potential adverse events of repurposed COVID-19 treatments before patients take them.

Outsourcing-Pharma (OSP) recently discussed the research—published in the Journal of Clinical Medicine​—with two TRHC leaders:

• Jacques Turgeon, chief scientific officer, TRHC
• Veronique Michaud, chief operating officer, TRHC Precision Pharmacotherapy Research and Development Institute

The two researchers told us about the aims of the study, what it revealed and the benefits associated with simulation analysis.

OSP: Could you please tell us more about Tabula Rasa Healthcare—who you are, what you do, key services and specialties, and what sets you apart from the competition? ​

JT: TRHC is a leader in providing patient-specific, data-driven technology and solutions that enable healthcare organizations to optimize performance. We improve patient outcomes, reduce hospitalizations, lower healthcare costs, and manage risk.

Our advanced proprietary solution, MedWise, cumulatively compares how medications interact together, all at the same time.  MedWise, provides pharmacists, a powerful tool to use for risk mitigation and clinical intervention to improve a patient’s drug regimen.

OSP: Similarly, please tell us about the Precision Pharmacotherapy Research and Development Institute.​

JT: The TRHC Precision Pharmacotherapy Research and Development Institute (PPRDI) is committed to the development of proprietary products, as well as their validation and recognition by the scientific and regulatory communities to optimize medication regimens in order to improve patient outcomes, reduce utilization of various healthcare services, lower healthcare costs, and manage risk. The PPRDI’s research vision expands with the emerging research initiatives that include bioinformatics, biomedical engineering systems, nanoscale science, patient-specific information, data-driven technologies and solutions, and translational research.

Based in the Lake Nona Medical City area of Florida, the PPRDI collaborates and partners with major academic and pharmaceutical partners in the region. PPRDI faculty conduct research using pharmacokinetics and pharmacodynamics modelling, computer simulations, and computational modelling using healthcare data from large databanks. The overall objective of this research group is to maintain and update existing products and develop new products associated with medication risk mitigation and medication risk stratification.

OSP: Please tell us about your MedWise technology, i.e. how it works and how it was put to use for this study.​

VM: MedWise helps manage medication regimens and enhance patient safety by identifying accumulative multi-drug interactions. Incorporating our proprietary Medication Risk Mitigation Matrix and MedWise Risk Score (MRS) technology, MedWise delivers point-of-care clinical decision support tools and precision dosing systems.

In the study, we utilized MedWise to determine each patient’s MRS, which is a predictive tool for adverse drug events (ADEs). Next, five repurposed COVID-19 drugs (or drug combinations) were added, one at a time, to patient drug regimens. The drug combinations included hydroxychloroquine, alone and in combination with azithromycin; chloroquine, alone and in combination with azithromycin; and lopinavir + ritonavir.

OSP: Could you provide the most interesting or notable findings of the study—were there any surprises in the results?​

VM: Results demonstrated that the addition of each repurposed drug caused a rightward shift in the frequency distribution of MedWise Risk Score (MRS) values (p < 0.05) which indicates an increase in the risk for adverse drug events. The increase in MRS was due to an increase in the drug-induced Long QT Syndrome (LQTS) or CYP450 drug interaction burden risk scores.

Increases in LQTS risk observed with hydroxychloroquine + azithromycin and chloroquine + azithromycin were of the same magnitude as those estimated when terfenadine or terfenadine + azithromycin, used as positive controls for drug-induced LQTS, were added to drug regimens. Our results agreed with our stated hypotheses.

We were surprised however to see that the magnitude of the effects was similar to that observed with terfenadine, a drug removed from the market because of its risk of sudden death.

OSP: What is the significance and benefit of focusing on older adults taking multiple medications?​

VM: These are the people most at risk for infection by COVID-19.  They have several comorbidities that put them at risk and they take multiple medications that increase their risk of drug-drug interactions and adverse drug events (ADEs). Additionally, this population is typically excluded from clinical studies; through our simulation strategy we are able to gather important data for the population that will most likely need these medications.

OSP: How do you expect the information from this study will be put to use in the life-sciences industry?​

VM: The conclusion of our paper states how our results should be positioned: The simulation-based strategy performed offers a way to assess risk of ADE for drugs to be used in people with underlying medical comorbidities and polypharmacy at risk of COVID-19 infection without exposing them to these drugs.

Our study supports that an appropriate monitoring plan should be put in place such as the use of biodevices to monitor the QT interval in order to decrease risk of developing ADE and optimize drug safety. There are real implications for improving the new product development process to include research in broader populations, including the elderly, without putting them at risk during a clinical trial.

OSP: What else would you like to share about the study that we might not have touched upon in the above questions?​

VM: Our study used a simulation strategy based on a medication risk score assessment used clinically to improve drug safety and reduce risks of ADEs in people with underlying medical comorbidities and polypharmacy. Besides the current repurposed drugs tested, our strategy can be applicable to any new drug being proposed to be used for COVID-19 or other clinical situations.

As we do not know the benefit associated with some drugs, our approach allows for the estimation of risk in patients with polypharmacy without exposing them to these drugs.