Rehabilitation Outcomes for OI:Collaborating on Tracking Evidence/Data

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Danielle H. Melton, MDDirector of Amputee Program at TIRR-MH

Associate ProfessorPhysical Medicine & RehabilitationDepartment of Orthopedic Surgery

Disclosures

TIRR-MH Limb Loss Program DirectorParadigm Outcomes Medical DirectorScience Chair External Collaborative Panel LLPRPrinciple Investigator OPRA HDE UT HoustonPlanning Committee for POP CSP 2017

Amputee Coalition—Scientific Medical Advisory—Limb Loss Prevention Task Force

ACRM Limb Restoration Rehabilitation Co-ChairBCM Masters in Orthotics & ProstheticsMedical Life Care Planning Consultant

Institutional Affiliation

Texas Medical Center (TMC)Largest Medical Complex in the World

University of Texas—Houston, UTHealthMcGovern Medical School Orthopedic Dept--Fasted-growing in US

Memorial Hermann Hospital (MHH)Busiest Level I Trauma Center in WorldOriginal Life Flight, Red Duke

The Institute of Rehabilitation & Research (TIRR-MH)2nd in Nation for Rehab HospitalsUS News & World Report

OI—Holy Grail

Surgeon—”OI is a bad idea. They will all get infected and eventually fail”

or Epic Fail?

Paradigm Shifts

Perspectives of OI

TIRR Amputee Treating

MD

LLPRegistry Science

Chair

Paradigm WC

Medical Director

Risk

30+ yrs tracking dataPhysician DrivenPatient Outcomes

Patient AdvocatePatient SafetyMedical Ethics

Risk TolerantRisk Adverse

Data ElementsEvidence to Prove

5 patients Position PaperOI complications

17-20 patientsSelf-payInsurance IssuesProsthetic reimbursementComponent WarrantyConnector Classification Complication coverage

Interface with different registriesFDA approval, Insurance coverageLong-term Outcomes

Paradigm OI Position Paper

....must be more research with uniform clinical outcomes and functional measures to better confirm the comparative benefits/risks associated with varying OI technology/devices.

…..position is not to recommend the use of the OI surgical option over conventional patient-prosthesis interface

FDA approval

Medical Device Classification

Class 1 Lowest potential for harmOnly requires general controlsEx: elastic bandages, gloves

Class 2 Similar to other devices on the marketRequires general controls & specific controls(labeling, performance standards, postmarket surveillance) Ex: powered wheelchairs, infusion pumps

Class 3 Requires more than general or specific controlsto assure safety and effectiveness Ex: implantable devices*

*Osseointegration Implants are considered Class 3 Devices

FDA Approval

Safe Medical Device Act of 1990Pre-Market Approval (PMA) applications• Must submit for Class 3 device• Must include data from non-clinical and clinical studies• Inspection of manufacturing facilities and laboratories

Exemptions to Clinical Studies• Investigational Device Exemption (IDE)• Humanitarian Device Exemption (HDE)• Custom Device Exemption (CDE)

Unless Exempt, all investigational devices must be approved before the study is initiated

Investigational (IDE)

Investigational Device Exemption (IDE)

• Allows for collection of safety and effectiveness data• Feasibility study• Conducted to support PMA (Pre-Market Approval)• Plan approved by Institutional Review Board (IRB)• Must be approved by the FDA

Humanitarian (HDE)

Humanitarian Device Exemption (HDE)Orphan Drug Act (ODA) 1984Rare condition affecting small numbers of patients (fewer than 4,000 per year) makes it difficult to gather clinical evidence to meet the FDA standard of reasonable assurance and effectivenessLimb Loss, Amputations

Burden of Proof on device developers• Prior to marketing, submit HDE• Demonstrate no similar, legally approved device on market• No other way to bring device to market• Limited applications, Labeled Utilization (defined parameters)

Only 56 devices have been approved via the HDE mechanism since 1990

Custom (CDE)

Custom Device Exemption (CDE)Criteria (device must meet all to be considered for CDE)1. Necessarily deviates from devices available, performance standard or

premarket approval requirement 2. Not available or used by other physicians3. Not available for purchase or for dispensing upon prescription4. Not offered for commercial distribution through labeling or advertising5. Intended individual patient made in a specific form or meets the special

needs of the physicianCDE cases• Can only perform 5 procedures per year in OI context• Does not require FDA approval • FDA recommends patient protection measures followed• IRBs should be familiar with regulatory requirements• No defined labeling parameters

OI Design Systems

Systems/Implant DesignsSystems ImplantsScrew-Fixation OPRA

Press-Fit Fixation ILP(Endo-Exo Femoral Prosthesis OPL (OTN)

POP

Transverse Pins/Axial Compression Compress

Press-Fit Implants

OPL Osseointegration Prosthetic Limb [Aschoff]/[Al Muderis] AQ Implants (Germany)/Permedica (Italy)

ILP Integral Leg Prosthesis [Al Muderis] AQ Implants (Germany), Orthodynamics (Germany)

POP Percutaneous Osseointegrated Prosthesis [Bloebaum, Kubiak, Gilliland]—VA Utah DJO Surgical (Austin)

OPL-America[Al Muderis*] Zigg (Utah)

OTN Osseointegration The Netherlands[Frokle,Van de Meent] OTNI

Custom Devices [various—Hillock, Hugate, Rozbruch*, Allison] various

FDA Approval

Systematic Reviews

Systematic Reviews

Out of 226 studies:Only 7 studies eligible (5 cohorts, 2 cross sectional)10 different measurementsLimited level of evidence

Recommendations1. OI with Rehab may improve QoL, Function, Activity level2. All clinicians/researchers involved should use and publish data on

QoL, Function, Activity level3. Need agreement on standard set of instruments for consistency

Systematic Reviews

Instruments• Quality of Life (Dx specific, General)• Functional Level

– Pain (residual limb, phantom limb)– ROM, Muscle strength (hip)– Gait Quality (coronal plane)

• Activity—walking ability (TUG, 6MWT)• Energy cost (Physiologic Cost Index)• Indicators of participation (RTW)

System/Implant PropertiesStoma related problemsResidual limb painOsseo-perception

Follow Assessment Times(Meta-analysis)Pre-op, Post-op 1,2,5,10 years

Cost Effective StudiesPost surgery costs (socket comparison, perc. connectors)Implant survivalInfection ratesQoL improvements

Systematic Reviews

Recommendations• Outcome Measures• Complications• Biometrics• Skeletal Changes• Patient Reported OM (QTFA, SF36)• Economics• PFP

Matching Cohorts• Age• Gender• Etiology• Time since amputation• Residual limb length

PRISMA, GRADE system21 relevant studies—observationalQuality6 Moderate (QTFA)15 Low/Very low

Systematic Reviews

14 studies, Therapeutic Level5—II5—III4—IV

Patient selection CriteriaContraindications

Prosthetic Use, Walking, Quality of Life

Study CriterionINCLUSION1. Unilateral trans-femoral amputation2. Unsatisfactory prosthetic rehabilitation3. Above 18 years of age4. Physically & mentally healthy5. Skeletal maturity6. Sufficient bone integration and

clearance for device7. Suitable soft tissues 8. Normal range of flexion and adduction9. Hip muscle strength10. Normal contralateral leg function11. Psychologically suitable12. English for study requirements IRB13. Understanding of risks and benefits14. Accessible to investigational site15. Comply with study protocol, follow-up16. Signed informed consent for IRB

EXCLUSION1. Suboptimal bone viability2. Radiotherapy to target limb at any time3. Chemotherapeutics, cortisone (12 mo)4. Cardiorespiratory limitations (walking)5. Co-morbidity (contraindications)6. Co-morbidity affecting contra-limb

affecting walking7. Allergic to implant components 8. Infection within prior 12 months9. Tobacco use in previous 3 months10. Cognitive impairment11. Unrealistic expectations12. Concurrent medico-legal proceedings13. Currently in other clinical trials

Data Tracking Registry

Limb Loss RegistryNIH FundedMayo Clinic (Ken Kaufmann)

External Collaborative Panel (15)• Industry• Manufacturers• Academic Institutions• Clinicians• Informatics

Osseointegration RegistryFunding for 2 years (Navy)Walter-Reed (Jonathan Fosberg)

Functional Outcomes(PROMIS surveys, PEQ)

Surgical complications• Soft tissue infections• Bone infections• Fractures• Implant removal

Government Oversight Committee: NIH, DoD, VA, CMS and FDA

LLPR

OGA Registry

OGA Registry

OGA Registry

OGA Registry

• C

Complicated OI Issues

Transitioning from Military to Civilian• Prosthetists get paid by componentry based on L-codes• CMS coverage of L-codes• Insurance Coverage follows CMS rules• Miscellaneous code “99” codes (rare reimbursement)• Connectors billed as 99 codes• Are connectors considered class 2 or 3• Complications related to OI covered as Work Related

Perspectives of OI

CliniciansMD, CP,

PT

EvidenceRegistry

WCCMSFDA

Risk Risk TolerantRisk Adverse

Questions/Comments