Abstract
In order to improve epilepsy care, clinical practice guidelines need to focus on implementation and adoption. This summary of an American Epilepsy Society Annual Meeting symposium on implementation science reviews how this field offers a way to improve guideline utilization and help address knowledge-practice gaps. Historical examples in stroke and sepsis care, as well as present day examples in the treatment of status epilepticus, offer insight into how future guidelines can increase systematic uptake of evidence-based practices. The methodological tools of implementation science can also help address resource limitations and inequitable access to care. Future guideline development should incorporate implementation science practices to ensure the delivery of high-quality epilepsy care.
Introduction
The goal of clinical practice guidelines is to distill the best available evidence into recommendations for the end user clinician. Modern guideline development requires thoughtfulness about implementation and adoption. Otherwise, the best written, most detailed summary of the highest level of evidence risks being ignored. What good is the guideline if no one reads or uses it? How can guidelines advance epilepsy care for our patients? In this review, we will discuss the role of guidelines, how implementation science can help guideline utilization, and the importance of incorporating this methodology into future guideline development in epilepsy.
What is Implementation Science?
Implementation science is the scientific study of methods to promote the systematic uptake of evidence-based interventions into routine clinical practice, with the goal of improving the quality, effectiveness, equity, and sustainability of health care delivery. 1 In contrast to traditional efficacy research, which primarily examines whether an intervention works under controlled conditions, implementation science focuses on how, why, and under what circumstances evidence-based practices are successfully adopted, implemented, and maintained in real-world settings. 2
A core principle of implementation science is the recognition that interventions proven effective in one setting may not translate directly to other environments with different resources, organizational structures, patient populations, or sociocultural contexts. As a result, implementation science emphasizes the adaptation of quality improvement (QI) and evidence-based solutions to local conditions while preserving the core components responsible for effectiveness.2,3 This approach acknowledges that barriers such as workforce limitations, infrastructure variability, competing clinical priorities, and health inequities differ across settings and must be addressed through context-specific strategies rather than uniform dissemination alone.
To guide and evaluate implementation efforts, several conceptual frameworks have been developed, among which the RE-AIM framework is one of the most widely used and pragmatic. RE-AIM evaluates interventions across 5 dimensions:
The
What are Past Examples of Successful Guideline Implementation?
The Institute of Medicine first described clinical practice guidelines in 1990 as “recommendations intended to optimize patient care that are informed by a systematic review of evidence and an assessment of the benefits and harms of alternative care options.” 6 The guideline process has evolved over the years with the development of Grading of Recommendations Assessment, Development and Evaluation (GRADE) in 2000, the most widely used framework for developing guideline recommendations. 7 Both the American Epilepsy Society (AES) and the American Academy of Neurology use GRADE.8,9 Although AES is relatively new to guideline development, there are important lessons to be learned from other organizations and the successful implementation of 2 well-known guidelines: Get with the Guidelines (GWTG)—Stroke and the Surviving Sepsis Campaign.
The American Heart Association's (AHA) GWTG-Stroke campaign is the largest QI initiative in neurological care since its inception in 2001 as a pilot registry to identify gaps in stroke scare. In the first 5 years of becoming a national program, QI methodology led to an increase in patients receiving tissue plasminogen activator (tPA) in less than 2 h from 42% to 73%. 10 Subsequent versions of GWTG-Stroke like the Target: Stroke goal focused on a target window to <1 h and moved the needle from 25% of patients receiving tPA in the golden hour to 53% within 3 years of its implementation. 11 The success of these initiatives can be attributed to many factors including but not limited to a multidisciplinary oversight committee of key stakeholders, hospital-led QI initiatives, AHA provided education tools, recognition programs, and detailed data collection which also includes standardized outcomes metrics. Importantly, these efforts are reinforced by timely performance feedback, with monthly team reports and quarterly review to support continuous evaluation and improvement.
Stepping outside of neurological care, the Surviving Sepsis Campaign is the most impactful guideline developed in medicine since its first publication in 2004. The goal was to decrease sepsis mortality internationally by 25% over 5 years and early implementation was associated with a 20% relative risk reduction in mortality. 12 Through this process, the initiative also recognized that guideline development must include globally representative stakeholders to ensure that the breadth of published sepsis evidence is captured, that local resources and population demographics are explicitly considered, and that individuals responsible for local implementation are engaged as active contributors. 13 This inclusive approach was essential to minimizing oversight in the generalizability, acceptability, and feasibility of guideline recommendations across diverse health-care settings. Beyond clinical outcomes, the campaign's success lay in its ability to change practice across individuals, institutions, and countries using standardized performance metrics. Similar to GWTG-Stroke, Surviving Sepsis utilized a large coalition of stakeholders, but this time on an international scale. The committee grew to include physicians, advanced practice providers, pharmacists, nurses, and patient representatives. 13 Since its inception, the campaign continues to evolve to include more countries outside of North America and Europe and to translate the guideline into more languages. Importantly, the campaign has also highlighted a central principle of implementation science: guideline recommendations are often derived from specific clinical, demographic, and resource contexts, and their effectiveness, feasibility, and safety may not generalize across settings. Interventions proven beneficial in high-income countries (HICs) may be neutral or even harmful in resource-limited settings, where context-specific drivers of mortality—including underlying pathology, genetics, comorbidities, illness severity at presentation, and access to monitoring and critical care—differ substantially. For example, fluid resuscitation, a cornerstone of sepsis management in HICs, has been associated with increased mortality in randomized trials of adults with sepsis in Africa, suggesting that higher fluid volumes may worsen outcomes in populations with high prevalence of HIV/AIDS, malnutrition, and limited intensive care unit (ICU) access.14,15 These findings underscore the need for contextual adaptation, rather than uncritical adoption, of guideline recommendations. Recognizing this, the incoming committee chair, Dr Coopersmith, has called for implementation science to be embedded into the process of sepsis guideline development as part of the next evolution of guideline development. 16
Prior guideline development in neurology and medicine can serve as a useful roadmap for epilepsy guidelines. However, there will inevitably be unique challenges faced in developing and implementing guidelines. How can current evidence-to-practice gaps in epilepsy care inform the next generation of epilepsy guidelines?
Despite decades of work aimed at optimizing epilepsy care, and despite robust evidence and guideline development, significant gaps in clinical practice persist. Across regions, challenges related to education, stigma, treatment delays, and inequitable access to diagnostic and therapeutic resources continue to undermine patient outcomes.17–19 While many global initiatives have sought to reduce disparities in epilepsy and status epilepticus (SE) care, particularly in low-resource settings where treatment gaps are most pronounced, substantial barriers remain even in HIC. One contributing factor is the persistent evidence–practice gap, driven in part by a slow and leaky research-to-practice pipeline. Traditional conceptualizations assume a linear flow of evidence from research production to clinical implementation; in reality, the process resembles a funnel through which information is progressively lost at each stage. 20
This narrowing begins early, with research agendas shaped by national priorities and funding opportunities, which determine which studies are pursued. Even when research is successfully completed, not all findings reach the public domain. Negative or null results often go unpublished because investigators assume journals will reject them, yet these data may provide critical practice-based insights for clinicians adapting interventions to diverse patient populations. Additional leakage occurs during the creation of systematic reviews and guidelines, in which many published studies are excluded due to methodological criteria that favor highly controlled research settings. This complex situation idealizes the populations and contexts in which interventions are deemed “evidence-based,” even though real-world conditions may differ substantially. Compounding this issue is the time required for evidence to influence practice; estimates suggest that it can take 17 years for merely 14% of original research to benefit patient care, of which approximately 10 years represent the lag between guideline publication and meaningful update in clinical practice. 20
However, beyond structural leakage, another key problem is the assumption that evidence will automatically “flow” into practice. 20 In reality, clinicians, the recipients of research, are not empty vessels. They bring prior experiences, beliefs, and attitudes, and they operate within complex contextual constraints, including workflow pressures, team dynamics, resource limitations, and institutional culture. These factors profoundly shape the receptivity, perceived utility, and actual adoption of guidelines.17–20
Why This Matters: The Role of Implementation Science
Addressing these challenges requires more than disseminating guidelines; it requires building systems capable of delivering evidence-based care reliably and sustainably. Implementation science provides a structured approach for understanding and addressing the system-level, organizational, and behavioral determinants that influence whether evidence-based epilepsy and SE practices are used in real-world settings. 21 Rather than asking whether clinicians know the guidelines, implementation science asks why certain workflows, resources, or contextual barriers impede adoption—and how interventions can be adapted without compromising fidelity to core recommendations.
A central principle is to move away from the notion that only generating more evidence will solve the problem. We should also focus on designing protocols and workflows that fit local resource constraints to enable more adherence to guideline recommendations, while simultaneously advocating for structural improvements needed to fully realize those guidelines in practice. Within epilepsy and SE, implementation opportunities include workforce expansion through telehealth and Project ECHO (Extension for Community Healthcare Outcomes) models, earlier referral for epilepsy surgery, improved access to epilepsy monitoring units, community education to reduce stigma, digital tools to expand electroencephalography (EEG) access, and standardized SE pathways to optimize diagnosis, medication administration, and EEG availability.17,18,22
Status Epilepticus as an Exemplar of the Knowledge–Practice Gap
SE is a time-sensitive neurologic emergency in which delays in recognition and treatment correlate with increased morbidity, mortality, and ICU utilization. 23 Although guidelines for SE management have existed for decades, real-world care frequently diverges from evidence-based practice. Multiple studies have documented persistent delays, inadequate benzodiazepine dosing, and inconsistent escalation strategies across prehospital, emergency department (ED), and inpatient settings. 19 Up to 40% of patients receive no prehospital benzodiazepine therapy, 24 and when administered, benzodiazepines are underdosed in up to 78% of cases.25,26 Delays beyond 30 min are common despite the operational definition of SE as a seizure lasting more than 5 min. These delays are associated with progression to refractory SE and higher mortality. 27
Further variability exists in escalation to second- and third-line therapies. The SENSE registry showed substantial non-adherence to treatment protocols, suggesting therapeutic inertia and uncertainty in real-world settings. 26 The STEPPER study demonstrated treatment sequence is a major prognostic factor of failure to resolve SE and that optimizing first-line therapies and adherence to guidelines can potentially influence prognosis. 28 Diagnostic barriers also contribute to the knowledge–practice gap. Continuous EEG (cEEG) is essential for identifying and managing non-convulsive SE; however, access is unevenly distributed, with significant constraints in under-resourced settings. Moreover, SE management spans multiple disciplines—emergency medical services, ED physicians, neurologists, intensivists, pharmacists, and nurses—making it highly sensitive to disruptions in workflow, communication, and team roles. A complexity-science lens helps explain why small breakdowns in coordination can produce substantial variations in care.
Improving SE Care Through Implementation Science
Improving real-world SE care requires aligning evidence-based interventions with system capabilities and clinician behavior. Several initiatives exemplify this approach. The QuITT-SE (Quality Improvement in Time to Treatment of Status Epilepticus) trial is a multicenter, pragmatic, effectiveness-implementation hybrid study designed to reduce delays in first-line treatment for pediatric SE. Recognizing that delayed administration of benzodiazepines is common and associated with worse outcomes, the trial uses implementation science principals embedded in the trial design and allows for local QI work alongside standard interventions in order to improve the timeliness of care rather than testing a new pharmacologic therapy. 29
QuITT-SE employs a stepped-wedge cluster randomized design across multiple pediatric hospitals, allowing each site to serve as its own control while accounting for secular trends. The intervention consists of a standardized, scalable QI bundle that includes prioritizing the use of non-intravenous benzodiazepines, goal treatment within 10 min of seizure onset, co-location of items necessary for treatment, de-implementation of unnecessary assessments, developing electronic health record tools, and multidisciplinary engagement.
The trial evaluates both clinical effectiveness outcomes, such as time to benzodiazepine administration, ICU utilization, neurologic outcomes, and cost, and implementation outcomes using the RE-AIM framework. This dual focus allows assessment not only of whether the intervention improves care, but also what contextual features are associated with higher implementation rates. By explicitly integrating implementation science methods into the study design, QuITT-SE addresses a critical gap between guideline recommendations and real-world practice in pediatric SE management. The trial provides an important model for how pragmatic, system-focused interventions can improve time-sensitive neurologic care and offers a generalizable framework for scaling evidence-based SE treatment across health systems.
Similarly, at the University of North Carolina, local observations of treatment variability led to the development of a standardized SE order set within the EPIC electronic medical record. This initiative—From Guidelines to Bedside: Scaling a Status Epilepticus Management Bundle across North Carolina (G2B-SE Bundle)—targets delays, underdosing, and inconsistent sequencing by embedding guideline-aligned decision support directly into clinician workflow. Early implementation demonstrated substantial reductions in time to benzodiazepine and second-line therapy. 30 The project emphasizes tailoring to local resources, especially in rural EDs, and incorporates statewide online education and in-person “road shows” to identify barriers of SE management and support EEG implementation for ongoing SE care. While protocols improve care under existing constraints, the initiative also highlights the need for continued advocacy for equitable access to EEG and neurology resources.
Internationally, similar efforts support the importance of contextually informed implementation. In Colombia, a seizure emergency code modeled after stroke and trauma codes standardized workflows and improved treatment times by clarifying roles, reducing cognitive load, and streamlining escalation pathways. 31 This model was also implemented in a larger scale in collaboration with the Madrid Regional Health Department (SERMAS) in Spain. 32 In Mexico, an adapted SE code accounted for constraints in workforce, EEG availability, medications, and emergency infrastructure. The protocol incorporated time-based targets, simplified medication lists, and visual decision-support tools (posters in ER and neurology rooms), and used a modified 2HELP2B threshold to reflect local epidemiology and resource realities. 33
A multinational initiative also addressed variability in cEEG practice by producing the first structured Spanish translation of the American Clinical Neurophysiology Society ICU EEG nomenclature. Through a 3-phase, qualitative and consensus-driven process involving 45 physicians from nearly all Spanish-speaking countries, the project generated a linguistically inclusive lexicon to support training, research, and clinical implementation, thereby reducing communication barriers and promoting more consistent cEEG interpretation (submitted by Rubinos et al for publication).
Across all these examples, a unifying theme emerges: protocols must be evidence-based, context-sensitive, acceptable to end-users, and multidisciplinary in design. Implementation science provides the methodological tools to describe why resource limitations produce delays and variability—and to use those insights to advocate for system-level change. As SE and epilepsy care continues to evolve globally, integrating implementation frameworks will be essential to closing the gap between research and practice and ensuring equitable, timely, and effective treatment for all patients.
Conclusions
Moving the needle in epilepsy care requires shifting from evidence generation alone to ensuring timely, equitable, and sustained delivery of evidence-based care in real-world settings. Persistent gaps between guidelines and practice highlight the need for implementation science to identify contextual barriers, guide adaptation of proven interventions, and evaluate outcomes beyond clinical effectiveness. Standardized system-level strategies, such as EMR-integrated order sets and targeted education, demonstrate that meaningful improvements in epilepsy care can be achieved by optimizing implementation and not only by developing new therapies. The AES community is uniquely positioned to advance this effort by prioritizing areas with large evidence-to-practice gaps, embedding implementation science principles within local centers, integrating these approaches into research design and guideline development, fostering multicenter learning networks, and advocating for funding mechanisms that support implementation-focused research. Together, these actions are essential to ensuring that high-quality epilepsy care is disseminated through guidelines and delivered consistently and equitably across health systems.
Footnotes
Acknowledgments
The authors would like to thank Dr Craig Coopersmith for sharing his lessons learned from the Surviving Sepsis Campaign at the AES Annual Meeting and informing this discussion on guideline implementation.
Declaration of Conflicting Interests
The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Funding
The authors received no financial support for the research, authorship, and/or publication of this article.
