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The Methodology of Clinical Studies Used by the FDA for Approval of High-Risk Orthopaedic Devices
Jordan P Barker1, Stephen D Simon, Jonathan Dubin
11Departments of Orthopaedic Surgery (J.P.B. and J.D.) and Biomedical & Health Informatics (S.D.S.), School of Medicine, University of Missouri - Kansas City, Kansas City, Missouri.
Background:
The purpose of this investigation was to examine the methodology of clinical trials used by the U.S. Food and Drug Administration (FDA) to determine the safety and effectiveness of high-risk orthopaedic devices approved between 2001 and 2015.
Methods:
Utilizing the FDA's online public database, this systematic review audited study design and methodological variables intended to minimize bias and confounding. An additional analysis of blinding as well as the Checklist to Evaluate a Report of a Nonpharmacological Trial (CLEAR NPT) was applied to the randomized controlled trials (RCTs).
Results:
Of the 49 studies, 46 (94%) were prospective and 37 (76%) were randomized. Forty-seven (96%) of the studies were controlled in some form. Of 35 studies that reported it, blinding was utilized in 21 (60%), of which 8 (38%) were reported as single-blinded and 13 (62%) were reported as double-blinded. Of the 37 RCTs, outcome assessors were clearly blinded in 6 (16%), whereas 15 (41%) were deemed impossible to blind as implants could be readily discerned on imaging. When the CLEAR NPT was applied to the 37 RCTs, >70% of studies were deemed "unclear" in describing generation of allocation sequences, treatment allocation concealment, and adequate blinding of participants and outcome assessors.
Conclusions:
This study manifests the highly variable reporting and strength of clinical research methodology accepted by the FDA to approve high-risk orthopaedic devices.
Insights
Clinical trial reporting for high-risk orthopedic devices approved by the FDA shows significant variability. Methodological strength, including blinding and allocation concealment, was often unclear in research supporting device approval.
Area of Science:
- Orthopaedic device research
- Clinical trial methodology
- Regulatory science
Background:
- High-risk orthopaedic devices require rigorous evaluation for safety and effectiveness.
- The U.S. Food and Drug Administration (FDA) oversees the approval process for these critical medical devices.
- Understanding the quality of clinical evidence supporting FDA approvals is essential for patient safety and healthcare policy.
Purpose of the Study:
- To critically assess the clinical trial methodologies used by the FDA for high-risk orthopaedic device approvals.
- To evaluate the period between 2001 and 2015 for trends in research quality.
- To identify potential weaknesses in study design and reporting that could impact the reliability of safety and effectiveness data.
Main Methods:
- Systematic review of 49 clinical trials for high-risk orthopaedic devices approved by the FDA (2001-2015).
- Audited study design and methodological variables to assess bias and confounding.
- Applied the Checklist to Evaluate a Report of a Nonpharmacological Trial (CLEAR NPT) to randomized controlled trials (RCTs), focusing on blinding and allocation concealment.
Main Results:
- Most studies were prospective (94%) and controlled (96%), with a majority being randomized (76%).
- Blinding was inconsistently reported and applied; outcome assessors were clearly blinded in only 16% of RCTs.
- Over 70% of RCTs received an 'unclear' rating for allocation sequence generation, concealment, and participant/assessor blinding via the CLEAR NPT.
Conclusions:
- Significant variability exists in the reporting and methodological rigor of clinical research supporting FDA approval of high-risk orthopaedic devices.
- Gaps in methodological reporting, particularly concerning blinding and allocation concealment, were prevalent.
- The findings highlight a need for standardized, robust research methodologies in the evaluation of orthopaedic implants.
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