Present:

Members and government liaisons reviewed and approved the summation report from the July 2004 meeting of the Orthopaedic Device Forum (Forum). Participants disclosed potential conflicts of interest.

Donna-Bea Tillman, PhD, Director of the Office of Device Evaluation in the Center for Devices and Radiological Health (CDRH) of the Food and Drug Administration (FDA) presented a Medical Device User Fee Modernization Act (MDUFMA) update.

MDUFMA was signed into law on October 26, 2002. Provisions include user fees for device reviews, establishment inspections conducted by accredited third parties, and new regulatory requirements for reprocessed single-use devices.

The CDRH challenges include: rapid technological changes, increasing complexity of devices, public demand for more control over healthcare, global marketplace and global regulation, and shrinking staff numbers. The influx of resources from the MDUFMA enables the hiring of additional staff. The Medical Device Fellowship Program in FY 04 supported 15 physicians, 42 engineers, 2 physicists, and 5 scientists.

MDUFMA funds are also being allocated to improve information technology infrastructure for tracking, reviewing, collaborating, managing correspondences, and archiving pre-market approval (PMA) submissions. Decision times for PMA submissions are decreasing to less than 320 FDA days, which includes weekends. The CDRH is also meeting first action criteria by sending major deficiency letters within 150 FDA days 84% of the time and other actions 96% of the time within 180 FDA days in FY 04. The goal for a final decision on 510ks is 90 days.

The CDRH workload is changing as they are receiving more of the following: expedited submissions, combination product submissions, modular PMAs and 510k submissions with clinical data. Strategies to surpass the MDUFMA goals include better communication between CDRH staff, and between CDRH and industry. Project managers are assigned submissions and will use information technology to support their process. Guidance documents and open public meetings will assist in providing a transparent process with clearly defined expectations. The CDRH is retrospectively analyzing peer-assessment of sample reviews in a pilot project.

The Division of General Restorative and Neurological Devices (DGRND) of the CDRH/ FDA suggested review of the following common submission problems in clinical trial reporting.

Top 9 PMA Submission Problems

1. Inadequate information about patient accountability
   100 patients may have been enrolled in the trial originally but only 75 were seen in follow-up at later time points. What is known about the missing patients? At each time point where data are reported, which patients are included and which are excluded? What impact does the missing data have on the trial results?
2. Reporting percentages
   If 25% of the patients are noted to have a complication in the trial, is that 25% of the original 100, or 25% of the 75 patients who were seen for longer-term follow-up? Include an explanation of how percentages are determined or provide them with numerators and denominators.
3. Safety information
   
   1. Sometimes the way in which events are defined does not allow for making a useful comparison to the control group. For example, if 3 patients had each of the following events in the treatment group: abscess, sepsis, wound dehiscence, and purulent drainage, and no patient had such an event in the control group, comparing the events in the two groups separately for each event may not illuminate a potential important safety issue.
   2. Specific information on safety event, especially serious safety events, such as duration, method of treatment, and extent of resolution or sequelae, may be very important.
4. Clinical trial protocol
   A copy of the clinical trial protocol according to which the study was conducted should be included. If the protocol was modified after the outset of the study, the FDA often requests the "change history" of the protocol. If protocols are modified, addressing their impact on the analysis of the data and/or clinical interpretation is helpful.
5. An analysis of the trial according to the protocol should be included, even for those cases in which sponsors wish to present alternative or additional analyses.
6. The impact of baseline values and/or demographic differences of the study results are not always discussed in the submission, and may lead to questions in the review process.
7. Sometimes data are submitted without a summary and interpretation of the results. It is important to include a discussion of why the information submitted supports safety and effectiveness of the device for the indication or intended use.
8. If the methods used to compile a table are not clear, the submission may be confusing. For example, the definitions of terms used in a table may be ambiguous and on occasion the same terms are used elsewhere in the submission with a different meaning.
9. A poorly organized submission, with an inaccurate table of contents, without proper pagination (e.g.- repeat page numbers, sections without page numbers) and with tables inaccurately identified, can prolong the review. Although this issue would not lead to a major deficiency, it can make the submission review unnecessarily challenging.

Innovation/ Stagnation
The Chantilly Revisited subcommittee was initiated to examine the mission of the Forum. While many Forum members have experienced a long tenure, the Forum intends to remain an active force in bringing new orthopaedic technologies to patients in a timely fashion. Forum members are encouraged to communicate with their respective organizational leadership in an effort to convey the accomplishments of the Forum and to solicit feedback on future directions.

The Chantilly Revisited subcommittee has developed a list of potential projects to address. The subcommittee initially discussed and worked on a comment in response to the FDA Innovation/Stagnation Critical Path document. Some projects require a legislative solution while others may require educational or regulatory solutions. Coalitions with other medical specialty organizations were discussed as another option to achieve some mutually agreed upon goals.

Research scientists commented that biologics companies have gone out of business for many reasons, not the least of which is a lack of scientific development in the tissue-engineering field. Other barriers to the market include technological, regulatory, and financial issues. The Forum chairman suggested choosing a particular technology, such as radiostereometric analysis (RSA), and proceeding with a test case to examine potential barriers to marketing in the U.S.

In past years, device inventors tested prototypes for devices in a few patients and later assessed the outcomes. Currently, the FDA requires the submission of an investigational device exemption (IDE) regardless of the size of a clinical trial. Some manufacturers commented that the U.S. is lagging behind other countries in terms of device development.

Further, Forum members encouraged collaboration between Health and Human Services (HHS) agencies. The National Institutes of Health (NIH) Roadmap Initiative serves as an appropriate model to identify gaps in biomedical research that the agency as a whole must address. A Forum member suggested that the NIH investigate RSA as a measurement tool to aid in reliable assessments of radiographs.

Orthopaedists acknowledge that study sections are risk averse and that innovation is not often appreciated in grant applications. A scientist encouraged grant submissions to several of the NIH institutes, rather than relegating all applications to one institute.

The Forum will send the draft list of potential projects to the Forum for comment. Subsequently, the AAOS members will share the draft list with the AAOS Board of Directors to sense their prioritization. Potential areas of development include:

Hip Guidance
The "Clinical Trial Design for Hip Replacement Systems" document has been submitted to the FDA. The draft document will be sent out for notice and comment as a guidance document but will likely include more specificity. A mandatory performance standard will be included in the draft guidance.

Orthopaedic surgeons commented that they believe there are a group of devices that are improved by subsequent iterations. While objective performance criteria are not common in orthopaedics, their application may prove to be useful in this guidance document.

Mobile Bearing Knees
Forum members discussed the status of the OSMA mobile bearing knee petition. Prior to reclassification, special controls documents must be developed. Special controls documents, such as guidance documents, will provide a reasonable assurance of safety and effectiveness for the intended use.

OSMA will form a special task force to develop recommendations on revisions to their mobile bearing knee petition. Special controls are needed to address each of the different types of design combinations including mobile bearing total knees and unicompartmental knees.

Standards
The American Society for Testing and Materials, Int. (ASTM) will be held in Washington, DC, November 9-12, 2004. The ASTM spring meeting will be held in Reno, NV on May 17-20, 2005. A symposium on the cleanliness of implants will be featured at the Reno, NV meeting, where issues involving cleaning, analysis, regulatory agencies, and the clinical impact of residues will be discussed.

Forum members reiterated the desire to increase the profile and participation in the use, development and adherence of medical/surgical standards. The AAOS will seek representation with the American Orthopaedic Association, International Orthopaedic Presidents, and Bone and Joint Decade international fellowship.

The Tissue Engineered Medical Products (TEMPS) division of the ASTM is balloting a guidance document on osteoinduction. The cartilage draft guidance has added a section on mechanical testing. Many standards are near completion; therefore TEMPS subcommittees are seeking new challenges. Forum members suggested adding a critical size bone defect model. The AAOS Biological Implants committee will assist in the review and refinement of that standard when it becomes available.

FDA Guidance Update
A Forum subcommittee continued review of the guidance document on Preparation of Investigational Device Exemptions and Premarket Approval for Bone Growth Stimulator Devices. The subcommittee recommended a change of the definition of a non-union. The subcommittee suggested that a nine-month time period is too long for patients to accommodate without treatment. The clinical consensus was to change the timeline to three months to accommodate the standard of care in most cases. Additionally, orthopaedic literature defines a non-union as no demonstrated change in healing on serial radiographs over a three-month period (Brighton, CT, Pollack SR: Treatment of recalcitrant non-union with a capacitively coupled electrical field: A preliminary report JBJS 1985; 67:577-585). Forum members delineated the issues in a memorandum. The amended guidance will be sent to the FDA.

Educational Program
Forum members will continue to move forward with plans to provide educational programs to the FDA staff. Two programs are budgeted for 2005. Bone void fillers and cartilage are possibilities for the spring session while the fall session might address small volume products to include finger and toe devices.

Artificial Disc Guidance
The ad hoc artificial disc subcommittee is nearing completion of the draft guidance. After review by Forum members, the guidance will be labeled a "proposed draft guidance" and sent to the FDA.

Forum Member Transition Issues
The Forum has many long-term members and must assess member transition issues. Forum members discussed developing job descriptions for each member organization and aligning those with overarching Forum goals.

Biologics Issues
The Center for Biologics, Evaluation and Research (CBER) sponsored a Critical Path workshop on October 7, 2004. The goal of the workshop was to provide a forum for stakeholders to discuss possible opportunities for and potential approaches to the development of innovative scientific knowledge and tools to facilitate the development and availability of new biological products including vaccines, blood and blood products, and cellular, tissue and gene therapies. Select breakout sessions focused on tissues and tissue engineered products.

Participants conferred a need to have more clarity on definitions of homologous use as applied to human tissue and bone. Stakeholders requested the development of test methods as new adventitious agents arise in biological substances. Further, stakeholders encouraged the FDA to develop a database to contain pre-clinical biological studies; however, the data is proprietary and will not be publicly available. The National Institutes of Health is developing a database with some information from gene therapy trials.

Military Issues
The AAOS seeking line itemizations for trauma research from the Department of Defense (DoD). Eighty per cent of war injuries are wounds to the extremities. The AAOS is encouraging its fellows to apply for research grants through the DoD.

Forum members discussed that the Society of Military Orthopaedic Surgeons (SOMOS) is now a member of the Council of Musculoskeletal Specialty Societies (COMSS) and may be a valuable resource. Surgeons noted that training programs to learn how to collect useful data as participants in clinical trials would be very useful. After discussion, the Forum decided to initiate a subcommittee to address DoD issues.

Cartilage Guidance
The Forum will assess the cartilage guidance at the spring 2005 meeting. Workgroup participants still have questions on where to define the clinical endpoints.

Pediatric Device Issues
A pediatric stakeholders group met in Washington, DC to assess and provide recommendations to members of the U.S. Congress on ways to increase pediatric device development. Amendments to the Humanitarian Device Exemption are being drafted by members of the stakeholders group.

FDA Update
The "Clinical Trial Consideration: Vertebral Augmentation Devices to Treat Spinal Insufficiency Fractures" guidance document will be posted on the CDRH website.

The first U.S. artificial disc, CHARITETM, was approved on October 26, 2004. The device is indicated for spinal arthroplasty in skeletally mature patients with degenerative disc disease (DDD) at one level from L4-S1. DDD is defined as discogenic back pain with degeneration of the disc confirmed by patient history and radiographic studies. These DDD patients should have no more than 3 mm of spondylolisthesis at the involved level. Patients receiving the CHARITE Artificial Disc should have failed at least six months of conservative treatment prior to implantation of the CHARITE Artificial Disc.

NIAMS

• The National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) funding opportunities for the Muscle Biology Branch, Musculoskeletal Diseases Branch, Multi-Program, and Skin Diseases Branch Program Announcements are located: http://www.niams.nih.gov/rtac/funding/grants/palist.htm
• RESEARCH ON MICROBIAL BIOFILMS
  Several NIH Institutes including the NIAMS and the National Institute of Dental and Craniofacial Research (NIDCR) invite research grant applications to conduct studies on microbial biofilms leading to improved strategies to diagnose, prevent and treat biofilm-associated infectious diseases. Collaborative projects, both domestic and international, that bring together investigators in diverse scientific disciplines studying biofilms, including microbiology, immunology (including mucosal immunology), biochemistry, clinical medicine, pathology, bioengineering, material science, imaging technology, and mathematical modeling are encouraged. http://grants1.nih.gov/grants/guide/pa-files/PA-03-047.html
• The NIAMS intramural research position is available in orthopaedics. For more information: http://www.irp.niams.nih.gov/
• NIAMS is currently recruiting orthopaedists to serve on study sections to review grant applications.

CMS

• The Centers for Medicaid and Medicare Services (CMS) continues to assess the use of spinal fusion in the Medicare population.
• CMS continues to introduce pay-for-performance programs. Through collaborative efforts, CMS is developing and implementing a set of pay-for-performance initiatives to support quality improvement in the care of Medicare beneficiaries.
• CMS will issue a national coverage decision on ultrasonic osteogenic stimulators to aid in fracture healing. Public comments have been received and CMS will post a proposed decision memorandum on January 27, 2005. National decisions must be issued within nine months. Forum members were reminded that 90% of coverage decisions are determined at the local carriers’ office.

Registry
The AAOS is moving forward with the American Joint Replacement Registry (AJRR). Legal review has delayed the initiation of data collection, but the Board of Directors anticipates data collection in the spring of 2005. The pilot project will collect data for one year.

CBER

• The Center for Biologics, Evaluation and Research (CBER) has appointed Edward Otto, PhD, as the new office director of the Office of Cellular, Tissue and Gene Therapies of the FDA.
• CBER and the Center for Devices and Radiological Health (CDRH) are collaborating on a workgroup to define regulatory issues with combination products.

OSMA Update

• Ms. Pamela Adams has been named as the new industry representative to the FDA Orthopaedic and Rehabilitative Device Panel.
• Orthopaedic industry representatives are anticipating Federal Register notices on spinal cages and external fixation devices.
• European Union reclassification on orthopaedic devices has not yet occurred. U.S. industry is still hopeful that the reclassification can be averted.
• OSMA continues to develop modifications to the metal-on-metal hip reclassification petition.
• OSMA may draft a guidance document on demineralized bone graft substitutes.

AAOS BOD Update

• Robert H. Haralson III, MD, MBA is the new AAOS Executive Director of Medical Affairs. Dr. Haralson previously served on the AAOS Board of Directors as Treasurer and was active in the Board of Councilors for many years. Since 1992, he has served on the AAOS CPT-ICD Coding Committee, most recently as chairman.
• The AAOS Board of Directors recently approved a position statement on evidence-based guidelines developed by the Evidence-Based Practice Committee.
  http://www.aaos.org/wordhtml/papers/position/1163.htm
• The AAOS Board of Directors also approved the rating of the levels of evidence based on the rigor of study design as a means to sort through and rate the quality of surgical literature and grades of recommendations for summaries or reviews of orthopaedic surgical studies.
  http://www.aaos.org/wordhtml/research/comittee/evidence/ebpc_3.htm

AAOS Biological Implants Committee
Members of the Biological Implants committee will present "Tissue Engineering Applications for Sports Medicine" at the AAOS Annual meeting in Washington, DC, February 23-27, 2005. The committee will also sponsor a scientific exhibit on xenotransplantation and participate in an exhibit on antibiotic loaded bone cement.

The Biological Implants committee filed comments on allograft tissue storage with the Joint Commission on Accreditation of Healthcare Organizations (JCAHO). Additionally, members will participate in the American Orthopaedic Society for Sports Medicine (AOSSM) workshop on allograft tissue in January 2005.

AAOS Biomedical Engineering Committee
The ASTM fall meeting will be held in Washington, DC on November 9-12, 2004. A symposium on "Titanium, Niobium, Zirconium, and Tantalum for Medical and Surgical Applications" will be presented at ASTM Week with a co-chair representing the AAOS Biomedical Engineering committee.

The ASTM has developed a computer assisted orthopaedic surgery (CAOS) workgroup to draft standards for the emerging field of computer-assisted surgery. Initial work will focus on drafting definitions for standardized terminology for national and international computer assisted orthopaedic surgery standards. CAOS is the topic for the 2006 National Institutes of Health/AAOS symposium.