Randomized clinical trials (RCTs) remain the gold standard for generating high-quality medical evidence. However, surgical disciplines have seen relatively fewer RCTs compared to other medical fields, partly owing to challenges unique to surgical interventions. These include difficulties in standardizing surgical techniques across practitioners and settings, resource constraints, recruitment hurdles, and ethical concerns tied to equipoise. Consequently, a large proportion of clinical practice guidelines in surgery rely on limited evidence, sometimes leading to standard practices that are not optimally effective or potentially harmful. This article explores the potential for pragmatic clinical trials (PCTs) to address these barriers and to promote robust, generalizable evidence production in surgical care, reflecting perspectives from recent FDA initiatives and published guidelines.
The Challenges in Conducting Surgical Randomized Trials
Surgical RCTs face multifaceted obstacles. Standardizing interventions is complicated by surgeons’ differing expertise, preferences, and procedural variations. Funding and infrastructural support are limited, and the lack of regulatory mandates analogous to those for drugs and devices reduces external incentives to conduct RCTs. Ethical concerns centered on equipoise frequently arise, where surgeons’ entrenched beliefs bias against randomization, labeling new techniques as inferior or unsafe despite uncertainties. These challenges contribute to slow recruitment, hesitation around protocol adherence, and skepticism toward trial findings’ applicability, further hindering evidence uptake.
Pragmatic Clinical Trials: Bridging Evidence Gaps
Pragmatic clinical trials offer a design paradigm that balances methodological rigor with applicability to everyday clinical settings. Unlike explanatory trials focused narrowly on detecting efficacy under idealized conditions, PCTs are implemented under routine care environments and incorporate broader patient populations and real-world practice variability. Such designs align with FDA’s mission to enhance evidence efficiency, generalizability, and patient-centeredness. For surgical trials, pragmatic elements may include offering surgeon-investigators latitude in patient enrollment criteria and surgical technique choice, reflecting authentic clinical decision-making while capturing efficacy across heterogeneous practice patterns.
Enhancing Trial Participation and Generalizability
Utilizing pragmatic trial features can mitigate resistance to enrollment by respecting clinician equipoise and judgement. For example, minimal exclusion criteria and allowing patients to be randomized only among treatment arms deemed relevant by their surgeon help ensure that randomization occurs where genuine uncertainty exists. Additionally, permitting procedural flexibility addresses surgeons’ concerns about standardized interventions potentially limiting trial relevance. These strategies promote broader inclusion, enhance external validity, and may expedite recruitment.
Streamlining Data Collection and Outcome Assessment
Data collection burden is a major resource challenge in surgical trials. FDA guidance supports embedding trial activities within routine clinical care, such as leveraging electronic health records (EHRs), registries, or administrative claims data to capture outcomes efficiently. EHR interoperability advancements enable standardized electronic data extraction across diverse health systems, reducing manual data entry and facilitating large pragmatic surgical trials. Moreover, focusing on patient-centric outcomes like quality of life, rather than exclusively surgeon-preferred metrics, addresses key dimensions of treatment impact relevant to patients, as exemplified by the CODA trial comparing antibiotics to appendectomy.
Challenges and Limitations of Pragmatic Approaches
Despite their promise, PCTs do not resolve all surgical trial challenges. Variability in patient characteristics and surgical techniques can dilute treatment effects, potentially biasing results toward null findings and complicating interpretation. Additionally, many hospitals lack registry participation, limiting registry-based trial generalizability, and insufficient surgeon training in pragmatic trial methodologies curtails adoption. Sustained institutional support, funding, and education are essential to build research infrastructure and expertise among surgical investigators.
Conclusion
Pragmatic clinical trials represent a viable path forward to enhance the quality, relevance, and efficiency of evidence generation in surgery. By adopting flexible, real-world trial designs that respect surgical practice variability and aligning outcomes with patient priorities, the surgical community can overcome longstanding RCT barriers. Strategic prioritization of clinically meaningful research questions, investment in trial infrastructure, and cultivating surgeon-trialist expertise are requisite steps. Success in these domains promises measurable advancement in surgical care quality and patient outcomes.
References
Abbasi A, Weltz A, Rivera DR, Nagel S, Mehta GU, Ashar BS, Cunningham SC. Opportunities for Pragmatic Design Elements in Surgical Trials. JAMA Surg. 2025 Oct 1;160(10):1133-1137. doi:10.1001/jamasurg.2025.3041 IF: 14.9 Q1 . PMID: 40864447 IF: 14.9 Q1 ; PMCID: PMC12452089 IF: 14.9 Q1 .