How Komodo’s Data Advantages can Support the Assessment of Federal Drug Safety Programs Like Clozapine REMS
As public health decisions incorporate higher volumes of more complex data, the importance of leveraging new data technologies and real-world evidence (RWE) to help inform regulatory outcomes becomes clearer. Regulatory and policy programs must be informed by real-world patient journey data and experiences, and the impact of those programs measured against outcomes. Komodo Health recently published a full-scale epidemiology study that could support key FDA decision-making with an in-depth evaluation of its Risk Evaluation and Mitigation Strategy (REMS) for the drug clozapine. Through research like this, Komodo could support federal regulators and stakeholders with essential insights to assess the true impact of its programs.
Clozapine, a vital antipsychotic medication indicated to treat schizophrenia, is linked to severe neutropenia, a rare but serious adverse event. Severe neutropenia is a condition in which the absolute neutrophil count (ANC) falls below 500 cells per microliter of blood, leaving the body highly vulnerable to infections due to the drastic reduction in white blood cells that fight off pathogens. To manage this risk, the FDA established the Clozapine REMS program in 2015 to oversee prescribing and monitoring, which requires patient ANC testing to track clozapine-induced neutropenia, and updated the program in 2019 to require a dedicated certification from practitioners prescribing and pharmacies dispensing the drug. The program aims to protect patients, but critics have argued that the costs may outweigh the benefits, due to medication interruptions, blocked refills, and testing errors that can lead to misreporting of adverse events and delayed access to treatment. Questions have arisen as to whether the increased barriers and disruptions of this update led to more harm than good.
Recently, the FDA called for a reevaluation of the program to better understand the real-world patient impacts of its risks and benefits. Using real-world data (RWD) from our extensive coverage of over 238 million patients in the Komodo Research Dataset and 73 million lab results in the Komodo Lab Results, we analyzed the impact of the 2019 REMS update (from 2017 through mid-2023) on neutropenia outcomes, looking at trends both before and after the update to identify key insights into the program’s effect on drug safety.
Methodology
The study included adults with at least one observable ANC value between January 2017 and July 2023 and at least one clozapine outpatient pharmacy dispensing up to 30 days prior to testing. Neutropenia was categorized as mild (1000-1499/μL), moderate (500-999/μL), or severe (<500/μL). The lowest monthly ANC value was indexed, with cohort re-entry allowed in subsequent months unless severe neutropenia occurred (requiring ANC recovery to ≥1000/μL). An interrupted time series (ITS) analysis using quasi-Poisson regression was conducted, comparing the pre-REMS update period (Jan 2017-Nov 2018, 3-month anticipatory period implemented) and post-update period (Mar 2019-Jul 2023).
The Clozapine REMS update resulted in an immediate rise in reported cases of mild neutropenia. However, month-to-month changes in the post-update period were minimal, indicating that while the REMS update had an immediate impact, its ongoing effect on neutropenia outcomes was relatively small with each additional month after March 2019. That is to say, the increase in mild neutropenia among clozapine users after the 2019 Clozapine REMS update may reflect earlier detection of neutropenia as intended by the program.
The findings from this study offer critical RWE that may be used as reference to support evaluations of the Clozapine REMS program. Advantageous with our embedded HIPAA-compliant, pseudonymized tokens in the Komodo datasets, clinical information from laboratory results can now be readily accessible and conveniently enhances health services utilization observable from health insurance claims without any sacrifice of privacy preservation. Specifically, using medical and outpatient pharmacy claims from the Komodo Research Dataset linked to personal ANC values from the Komodo Lab Results, we were able to analyze neutropenia outcomes more rapidly and comprehensively than typical claims-based RWE studies or investigations using data linkage via traditional methods — while similar analyses using legacy approaches could take years, Komodo completed this in-depth analysis in two months. This speed and depth are crucial in regulatory decision-making, particularly for federal programs aimed at drug safety, such as REMS. Our study not only provides key stakeholders with timely data but also contributes to the broader conversation about public health efficacy, where patient safety must be balanced with accessible care.
Citizen participation around the Clozapine REMS program reflects public concern that, while designed for safety, such programs may inadvertently limit access to life-saving medications. In this context, the role of RWE is indispensable. By analyzing vast, real-world healthcare data, we enable regulatory bodies like the FDA to measure the program's effectiveness and address key questions about its impact on patient outcomes. Our results demonstrate the full potential of readily available dataset linkage and provide a scientific basis for evaluating health policy and program in the defense of public health.
Looking to the Future
Komodo Health’s groundbreaking approach to healthcare data allows for rapid and accurate linkage of medical and laboratory data, enabling stakeholders to answer critical scientific questions about the program's efficacy. By focusing on the data, we help inform public health decision-making, offering insights into how federal safety initiatives may benefit patients at the population level. With readily accessible, linked datasets, we can accelerate understanding and contribute meaningfully to the ongoing evaluation of federal health programs.
Read the full study on the ISPOR or ISPE 2024 sites, or see more Komodo-driven peer reviewed research, like our recent paper on multiple sclerosis.
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