This is an application for a K23 award for Dr. Gabriela Schmajuk, a rheumatologist and health services research at the University of California, San Francisco (UCSF) and the San Francisco Veterans Affairs Medical Center (SFVAMC). Combined with a training plan focused on advanced biostatistical methods, qualitative techniques, and health policy, the goal of the current study is to use rich administrative and electronic health record data to develop a rational approach to drug toxicity monitoring using methotrexate, the first-line treatment for patients with inflammatory arthritis, as a model drug. Building upon her prior work which evaluated quality measures and patient safety in rheumatoid arthritis and systemic lupus erythematosus (JAMA 2011;305(5):480; Semin Arthritis Rheum 2011;40(6):559), the proposed series of projects will provide a framework to characterize the outcomes of current drug toxicity monitoring practices (including unintended harms) and individualize monitoring strategies that will improve patient outcomes and reduce health resource overuse. Although the National Quality Forum (NQF) recently endorsed several quality measures that address laboratory toxicity monitoring for outpatient drugs used in chronic rheumatic conditions, it is not known whether frequent toxicity monitoring in the absence of patient-reported symptoms leads to improved patient outcomes. On the contrary, stopping a drug due to benign or transient laboratory abnormalities can result in diagnostic and treatment interventions that are inappropriate, burdensome, and expensive. In the case of methotrexate, new NQF measures require testing of liver function tests (LFTs) every 12 weeks with the intent of reducing the incidence of hepatic fibrosis and cirrhosis. But frequent, untargeted monitoring, and the detection of potentially clinically insignificant LFT elevations, may have unintended consequences. For example, patients may have increased pain or disability if methotrexate is unnecessarily stopped, increased costs if they are switched to high-priced biologic agents, or increased harm if methotrexate is substituted by glucocorticoids, which have more long-term toxicities. The uncertainty around the effects of frequent, untargeted toxicity monitoring represents a critical gap in knowledge that hinders efforts to improve patient safety, reduce unintended harms, and maximize the quality of care for patients with rheumatic diseases.
Aims 1 and 2 of this proposal will leverage administrative and clinical data from the Veterans Affairs system to (1) assess current practice patterns and downstream consequences of liver toxicity monitoring among methotrexate users with inflammatory arthritis and (2) develop and validate a prediction rule that identifies patients at low risk of developing LFTx > 2 x the upper limit of normal and thus may be candidates for less frequent monitoring.
Aim 3 will convene focus groups of a diverse group of patients and clinicians to determine attitudes and identify barriers around using a potentially less intensive monitoring schedule for selected low- risk patients. The knowledge gained here will inform the next iteration of patient safety measures in this area, potentially reducing unnecessary testing while promoting screening that is effective. In addition, it will provide preliminary data for a R01 that will implement and test the value of a clinical decision support tool to guide medication toxicity monitoring for methotrexate users. The paradigm developed here can serve as a model for studying monitoring in other common clinical scenarios (for example, for users of anti-hypertensives, statins, or antidiabetic agents) where drug toxicity monitoring plays a key role in medication choice and disease management. Dr. Schmajuk has assembled an exceptional mentorship team with expertise in issues of medication monitoring, quality of care, and rheumatic diseases, as well as experience in using national VA data to address these questions. She will have access to a rich research environment, including the UCSF Arthritis Research Group and the San Francisco VA Geriatrics division, with their respective work-in-progress seminars, biostatisticians, and large faculties with similar research interests to mine. The resources of the SFVAMC and our academic affiliate will provide me with training opportunities, including a second year of VA Quality Scholars Fellowship and enrollment in the UCSF Training in Implementation and Dissemination Sciences Program. Dr. Schmajuk's long term goal is to become a rheumatologist at a leading academic institution where she can pursue an independent research career in health services research. Her research agenda will address the questions of quality of care, drug utilization, and drug safety for patients with rheumatic diseases. This mentored career development award will provide the skills, mentorship, and experience necessary to propel her to independence.
Methotrexate is an oral drug used as the first-line treatment for autoimmune arthritis which can be toxic to the liver in some patients. The goal of this project is to find a method of targeting laboratory monitoring to patients at higher risk for liver damage and thereby improve patient outcomes and reduce total healthcare costs.
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