Measuring Real-World Guideline Concordance and Outcomes of Major Depressive Disorder Pharmacotherapy
Open Access
- Author:
- Breitzig, Mason
- Graduate Program:
- Epidemiology (PhD)
- Degree:
- Doctor of Philosophy
- Document Type:
- Dissertation
- Date of Defense:
- February 08, 2024
- Committee Members:
- Duanping Liao, Professor in Charge/Director of Graduate Studies
Erika F H Saunders, Co-Chair & Dissertation Advisor
Lan Kong, Outside Field Member
Jeffrey Yanosky, Major Field Member
Duanping Liao, Co-Chair & Dissertation Advisor
Guodong Liu, Outside Field Member
Daniel Waschbusch, Outside Field Member
Nancy Olsen, Outside Unit Member - Keywords:
- Major depressive disorder
Guideline concordance
Pharmacotherapy
Patient-reported outcomes
Quality control metrics
Clinical epidemiology
Real-world clinical data
PCARES - Abstract:
- Major depressive disorder (MDD) is a heterogeneous, multifactorial, and multigenic syndrome with a poorly understood etiology and a diagnosis that remains reliant on overt phenotype. This is despite major depressive episodes impacting over 8.3% of adults in the United States between 2020 and 2021, rapidly rising in prevalence among youth for many years prior, and incurring a national economic burden beyond $334 billion in 2019. Research has turned to basic science and measures of real-world patient progress to combat this mounting burden, especially in the aftermath of COVID-19. Despite notable advancements in the past two decades, the treatment of MDD remains a trial and error process, compelling clinicians to artfully prescribe and treat using observed response, acceptability, and tolerability. Various clinical guidelines seek to lend objectivity to this art, but sparse information on their real-world impact hinders their utility. Furthermore, the development of these guidelines, though a robust and systematic synthesis of evidence-based medicine, is often unidirectional: informed by robust and restrictive clinical trials but rarely incorporating lived experiences and evidence from clinical practice. Guideline concordance, the degree to which clinicians implement the MDD treatment recommendations from clinical guidelines in their daily practice, represents an opportunity to address critical issues with contemporary MDD research and practice via measuring the uptake of clinical guideline recommendations in real-world clinical settings. However, the research on guideline concordance for MDD has been as heterogeneous as the disorder itself. Studies have used various idiosyncratic and often overly simple and independent criteria to evaluate this construct, neglecting to measure a range of nuances and heterogeneity in the treatment guidelines and practice. Furthermore, the literature overlooks the vital connection between clinical guideline recommendations and real-world patient outcomes. Until now, measuring guideline concordance dynamically and thoroughly has been difficult or even unfeasible, but electronic medical records afford new opportunities to overcome this. Measuring guideline concordance stands to improve the care and research of MDD in two distinct ways: (1) elucidating the magnitude of known or suspected treatment gaps and identifying new ones based on the heterogeneity and nuance of MDD presentation within large natural clinical populations; (2) helping researchers and clinicians assign priority to presentations of MDD and their corresponding treatment recommendations. Current treatment paradigms emphasize optimizing care via observation, communication, and measurement. Quantifying which patient subgroups have the most significant risk of poor treatment and which guidelines are most strongly associated with recovery, the ultimate goal of MDD treatment, would provide clinicians with valuable and actionable real-world information on optimizing care. The final boon of measuring guideline concordance is the prospect of providing more timely data on current practices that may help reverse the unidirectionality of clinical guidelines and supplement the rigorous research data therein with information on what works in the real world. This dissertation proposes a novel algorithm for quantifying the degree of guideline concordance in a clinical population of 1,403 patients with MDD from the Penn State Psychiatry Clinical Assessment and Rating Evaluation System registry (PCARES). Chapter 1 describes the historical and present-day epidemiologic burden of MDD. It also discusses the clinical course of MDD and current treatment paradigms. Chapter 2 summarizes the state of the science for guideline concordance: evaluating clinical guidelines, their application in practice, and the knowledge gaps between them. Chapter 3 then describes the research methodology, detailing the novel pharmacotherapy guideline concordance algorithm (GCA-8). Chapters 4-6 present data on the performance of the GCA-8 score in the PCARES cohort and its associations with (1) patient-reported MDD symptom severity compared to older metrics (Chapter 4), (2) sociodemographics and comorbidities (Chapter 5), and (3) patient-reported functioning (Chapter 6). Lastly, Chapter 7 summarizes this research's clinical and public health implications, strengths and limitations, and avenues for future research and the implementation of the GCA-8. In this dissertation research, a new and unique method of measuring pharmacotherapy guideline concordance in the treatment of MDD. The GCA-8 allows researchers and clinicians to quantify the uptake of clinical guidelines across patients with various MDD presentations and treatment approaches. The timeliness of this research is underscored by the renaissance of measurement-based care and the advent of learning health systems. The GCA-8 is a natural addition to the system-wide quality control that these paradigms implement, influencing practice with data from real-world clinical treatment patterns and patient outcomes. In theory, few differences between evidence-based practices and MDD treatment should exist if (1) the guidelines are sufficiently detailed and efficacious for many types of patients, (2) integration of care sufficiently occurs, and (3) concordance is appropriately measured (i.e., as detailed as the guidelines). Measuring guideline concordance allows researchers and clinicians to address these points while providing more information on the various treatment courses for those with MDD. The findings of this dissertation support an innovative quality control metric that is among the first to quantify the link between clinical guideline application, guideline concordance, and patient-reported MDD symptom severity and functioning using a reproducible metric. The results herein also characterize treatment gaps within a naturalistic clinical setting. Finally, as a product of the evidence they are based upon, clinical guidelines may lack resolution regarding the gamut of treatment approaches and MDD presentations experienced in the real world. Measuring guideline concordance has important clinical and public health implications by providing a mechanism to observe how evidence-based practices interact with a broader range of patient and clinician experiences. The future implementation of tools like the GCA-8 can supplement existing care quality measures and (1) detect new response patterns in patient subpopulations, (2) help prioritize patients based on new perspectives of staging, (3) provide a weighting scheme for clinical guideline recommendations, (4) help researchers understand treatment and guideline gaps, and, ultimately, serve as another tool to quell the rising burden of MDD.