# Clinical Informatics to Advance Epidemiology and Pharmacogenetics of Serious Cutaneous Adverse Drug Reactions

> **NIH NIH R01** · BRIGHAM AND WOMEN'S HOSPITAL · 2020 · $696,239

## Abstract

Project Summary
 Severe cutaneous adverse reactions (SCARs) are morbid immunologic reactions to drugs that confer a
mortality of 10-50%. Over the last decade, significant promise for prediction and prevention has come from the
discovery that many SCARs are associated with variation within HLA class I alleles. For HLA-B*15:02, this has
led to routine pre-prescription screening for carbamazepine in many Southeast Asian countries and a significant
reduction in cases of carbamazepine SJS/TEN. Despite this progress, there is little known about genetic and
epidemiological risk factors for SCARs related to commonly used drugs such as antibiotics. There is also limited
information about HLA risk for SCARs across the diverse populations present in the United States. Furthermore,
imprecision of clinical phenotyping and lack of standardized coding has led to challenges in finding SCAR cases
in the electronic health record (EHR). Our proposed study aims to address critical challenges and gaps in our
knowledge of antibiotic SCARs.
 In Aim 1, we will leverage advanced informatics and longitudinal EHR data for over 11 million patients from
Partners HealthCare System since the 1980s to identify SCAR cases. We will create, optimize and standardize
reproducible methods for finding SCAR cases and validating a cohort of SCAR patients. This iterative process
will be used to refine and disseminate an electronic phenotype to be validated cross-institutionally.
 In Aim 2, we will analyze SCAR prevalence and conduct a case-control study to identify drug-specific and
patient-specific risk factors for antibiotic-associated SCARs. We will compare clinical sequelae, quality of life and
adherence of SCAR patients compared to controls through validated survey instruments.
 In Aim 3, we will identify candidate HLA and genetic associations from patients with validated antibiotic-
associated SCARs. We will examine difference in genetic risk in minority and health disparity populations and
predict that we will be powered to establish HLA associations for vancomycin DRESS (i.e., drug reaction with
eosinophilia and systemic symptoms) and sulfonamide antimicrobial and beta-lactam SCAR. HLA alone, or
in combination with clinical risk factors, can lead to improved SCAR prevention and early diagnosis. We will
establish a data sharing platform, in the form of an online electronic phenotype and patient registry, that can be
used to enlarge SCAR cohorts for future large-scale genomics studies.
 The roadmap we develop will translate into the development of electronic phenotypes for serious adverse
drug reactions that facilitate genetic discovery. Knowledge gained will be crucial to the translation of genetic data
into clinical decision making. This is in close alignment with NIH’s research mission to accelerate genetic
discovery for iatrogenic and preventable drug-induced diseases that will translate into prevention, earlier
diagnosis and an enhanced mechanistic understanding that may lead ...

## Key facts

- **NIH application ID:** 10018800
- **Project number:** 5R01AI150295-02
- **Recipient organization:** BRIGHAM AND WOMEN'S HOSPITAL
- **Principal Investigator:** Li Zhou
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $696,239
- **Award type:** 5
- **Project period:** 2019-09-16 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10018800

## Citation

> US National Institutes of Health, RePORTER application 10018800, Clinical Informatics to Advance Epidemiology and Pharmacogenetics of Serious Cutaneous Adverse Drug Reactions (5R01AI150295-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10018800. Licensed CC0.

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