Maximizing Safety and Integrity in Orthopedic Clinical Trials with RBQM: A Strategic Approach by Denis Katz, MD

Maximizing Safety and Integrity in Orthopedic Clinical Trials with RBQM: A Strategic Approach by Denis Katz, MD

Introduction

Orthopedic clinical trials characterized by complex surgical interventions, device-specific variables, and extended rehabilitation follow-ups are prime candidates for Risk-Based Quality Management (RBQM). RBQM is an adaptive, data-driven quality framework that focuses oversight on what is most critical to participant safety and the validity of trial conclusions. In January 2025, ICH finalized the E6(R3) update to Good Clinical Practice, which explicitly embeds RBQM principles and encourages sponsors to integrate critical-to-quality thinking across the clinical development lifecycle.

Understanding Risk-Based Quality Management

RBQM is now the prevailing approach to clinical trial oversight in regulated drug, biologic, and device development. The core idea is proportionality: monitoring intensity and quality controls are aligned to the risks that matter for subject safety and decision-making endpoints, rather than applying uniform, resource-intensive methods such as blanket 100% source data verification. RBQM centers on identifying Critical-to-Quality (CtQ) factors, establishing Key Risk Indicators (KRIs) and Quality Tolerance Limits (QTLs), and using centralized analytics and targeted on-site activities to address high-priority issues.

Unique Risk Factors in Orthopedic Clinical Trials

The field of orthopedics introduces study-specific complexities that make RBQM particularly valuable:

• Surgical complexity and variability. Procedures range from minimally invasive arthroscopy to total joint arthroplasty, and variations in surgical technique, implant selection/positioning, and intraoperative decision-making are major drivers of outcome heterogeneity.

• Patient heterogeneity. Bone quality, baseline functional status, comorbid disease, and varying expectations for rehabilitation create broad within-cohort variance that must be accounted for in protocol design and risk assessments.

• Imaging and measurement variability. Structural endpoints (radiographs, CT, MRI) and clinician-reported measures often depend on reader interpretation; standardized imaging acquisition, centralized readers, and automated or semi-automated image analytics are critical to reduce measurement noise.

• Longitudinal follow-up and adherence. Rehabilitation, implant survivorship, and late complications require durable monitoring strategies that anticipate protocol deviations and loss to follow-up.

Implementing RBQM in Orthopedic Trials

Successful RBQM implementation must be cross-functional and pragmatic. Core steps include:

• Initial, cross-disciplinary risk identification (surgery, imaging, PROs, safety events) to define CtQs.

• Prioritization and mapping—classify risks by probability and impact and map them to monitoring actions (centralized analytics, targeted SDV, focused on-site visits).

• Technology and validation—select validated ePRO/eCOA platforms, imaging pipelines with audit trails, and central monitoring tools with configurable KRIs.

• Iterative reassessment—use rolling data reviews to scale monitoring intensity up or down; define pre-specified triggers for escalation.

Operationally, the FDA and other regulators recommend that sponsors document the RBQM approach in monitoring plans and quality systems as part of inspection readiness.

Technology and Data Analytics for Orthopedics

Modern RBQM relies on a technology stack that supports systematic risk detection and efficient remediation:

• AI-assisted imaging analysis. Machine-learning tools can automate segmentation, quantify joint spaces or callus formation, and reduce inter-reader variability when integrated into controlled central-reading workflows.

• Machine learning for signal detection. Statistical and ML-based surveillance of multicenter data can flag atypical patterns (safety trends, site-level data drift, missingness) earlier than periodic manual review.

• Wearables and digital biomarkers. Accelerometers, inertial measurement units, and smartphone-derived metrics capture real-world functional outcomes (gait, activity, step counts) that complement clinic-based measures and may provide higher-frequency endpoints for risk monitoring.

Regulatory and Economic Considerations

Regulators now view RBQM as a best practice for ensuring subject safety and data integrity; sponsors are expected to show thoughtful, documented risk assessments and monitoring plans. Industry surveys demonstrate rapid RBQM adoption across trial portfolios, and many organizations report meaningful operational efficiencies from the shift away from non-targeted, exhaustive SDV.

A commonly cited industry estimate is that monitoring and related activities account for a substantial portion of clinical trial budgets. RBQM and centralized monitoring approaches have been associated in the literature and industry analyses with sizable reductions in monitoring effort and cost in many programs, especially when combined with validated automation and eSource capture. Nevertheless, the precise savings will vary by study size, phase, and therapeutic area; therefore, sponsors should use study-specific modeling rather than rely on a single percent reduction figure.

Future Directions

Several trends will shape RBQM in orthopedics over the next several years:

• More quantitative imaging platforms that integrate automated segmentation and standardized metrics to minimize reader variability.

• Predictive analytics that identify patients at elevated risk for complications or poor functional recovery and allow pre-emptive protocol interventions.

• Distributed and hybrid data capture as eSource, ePRO, and wearables mature, they will shift the locus of verification from on-site paper checks to validated digital workflows that are inherently more auditable.

• Blockchain and immutable ledgers are actively being explored for audit trails and provenance, but these technologies remain largely in the pilot and proof-of-concept phase; regulatory expectations and standards for their routine use in pivotal submissions are still evolving.

Conclusion

RBQM is changing how orthopedic studies are planned and monitored by focusing resources on what matters most: critical safety signals and CtQ endpoints. Orthopedic trials where surgical technique, imaging interpretation, and functional outcomes introduce layered risk benefit substantially from RBQM when it is thoughtfully implemented, technologically supported, and documented for regulatory review.