Clinical Studies for Vertebral Body Augmentation Devices in Treatment of Insufficiency Fractures
This guidance provides information regarding clinical studies for devices used in spinal vertebral body augmentation to treat insufficiency fractures due to minor trauma, osteoporosis, or other lytic conditions. It covers both vertebroplasty and kyphoplasty procedures using PMMA bone cements and potential future materials like resorbable and permanent polymers.
What You Need to Know? 👇
What are the main clinical indications for vertebral augmentation devices according to FDA guidance?
The FDA recognizes two primary indications: compression fractures secondary to trauma due to osteoporosis, and insufficiency fractures secondary to osteoporosis or other lytic conditions. These devices treat fractures that occur from normal daily activities in weakened bone.
What control group options does FDA recommend for vertebral augmentation device clinical trials?
FDA recommends concurrent, randomized controls including accepted alternative treatments, legally marketed devices, specialized physical therapy, medication and bracing, or sham procedures using analgesics. Crossover studies are possible but require valid analysis at crossover time.
How long should clinical studies for vertebral augmentation devices follow patients?
FDA generally recommends a 2-year follow-up period for spinal fracture studies. These devices are considered permanent spinal implants since they remain in the patient’s spine for 30 days or more, requiring comprehensive long-term safety assessment.
What are the primary effectiveness endpoints FDA expects in vertebral augmentation studies?
Primary effectiveness parameters include pain and function assessment using validated scales (VAS, disability questionnaires), and maintenance or restoration of vertebral height or alignment using specific radiographic criteria. Secondary parameters include quality of life and ambulatory status.
What serious complications should be included in risk analysis for vertebral augmentation devices?
Risk analysis should address hypotension, hypoxemia, cardiac complications, pulmonary embolism, death, cement extravasation, adjacent fractures, neurological complications, and device-related infections. All potential complications from device components, delivery, and patient conditions must be considered.
What patient exclusion criteria does FDA recommend for vertebral augmentation clinical trials?
FDA recommends excluding patients with neurologic deficits, kyphosis >30°, compression >50%, translation >4mm, spinal canal compromise, burst fractures, infection, myelopathy, coagulopathy, pregnancy, and those with asymptomatic or prophylactic treatment needs.
What You Need to Do 👇
Recommended Actions
- Develop comprehensive clinical study protocol with defined inclusion/exclusion criteria
- Establish clear primary and secondary effectiveness parameters
- Implement robust safety monitoring system
- Create detailed risk analysis addressing all potential complications
- Develop comprehensive study monitoring plan
- Consider pre-submission meeting with FDA
- Ensure compliance with design control requirements
- Establish clear patient and study success criteria
- Plan for 2-year follow-up with regular evaluations
- Prepare well-organized submission addressing all special controls
Key Considerations
Clinical testing
- 2-year follow-up study recommended
- Regular interval evaluations with defined windows
- Concurrent randomized control recommended
- Success criteria based on:
- Pain and function improvement
- No secondary interventions
- Comparison to control group
- Inclusion/exclusion criteria must be clearly defined
Human Factors
- Assessment of pain and function using validated scales
- Evaluation of ambulatory status
- Quality of life measurements using validated scales
Safety
- Report all complications (device-related or not)
- Monitor for:
- Infections
- Secondary surgical interventions
- Neurological complications
- Serious adverse events
- Death
- Radiographic evaluations for:
- Material extravasation
- Adjacent fractures
- Osteolysis
- Material fracture
- Disease progression
Other considerations
- Comprehensive monitoring plan required
- Risk analysis must address all potential complications
- Pre-submission meeting with FDA recommended
- Well-organized submissions addressing special controls needed
Relevant Guidances 🔗
- Clinical Data Presentation for Orthopedic Implant Device Submissions
- Design Considerations for Medical Device Pivotal Clinical Studies
- Benefit-Risk Determinations for Medical Device Premarket Review
- Use of Real-World Data to Generate Evidence for Medical Device Regulatory Decisions
Related references and norms 📂
- 21 CFR 888.3027: Classification regulation for PMMA bone cement
- 21 CFR 812.3(d): Definition of permanent implants
- 21 CFR 820.30(g): Design control requirements for risk analysis
Original guidance
- Clinical Studies for Vertebral Body Augmentation Devices in Treatment of Insufficiency Fractures
- HTML
- Issue date: 2004-10-23
- Last changed date: 2020-03-19
- Status: FINAL
- Official FDA topics: Medical Devices, Premarket
- ReguVirta ID: 145fc40721ee0cdc84b40bee42fe3b35