Present:

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

The FDA realized that after the recent doubling the National Institutes of Health (NIH) budget, 80% of biological and drug products were not making it to the U.S. marketplace. The Critical Path initiative seeks to find the missing links between scientific discovery and marketable products. Products are failing later in the discovery process, predominantly in Phase III clinical trials.

Optimism for a well developed infrastructure was based on new biomedical discoveries including the sequencing of the human genome, genomic and proteomic technologies, advances in medical imaging, nanotechnology, tissue-engineering and new drug discovery. The matching acceleration of product development has been expected but most discoveries have not yet been transformed into new medical products. Because of the lack of investment in medical product development scientific infrastructure, the FDA is using unnecessarily cumbersome and insufficiently predictive product development tools.

With regard to devices, the FDA is seeking to identify and accomplish the science necessary to create tools for efficient product development. Additionally, they are searching for new evaluative methods and tools that assist product development.

For example, the FDA suggested that a study of 40,000 mammography patients was needed to prove that digital techniques were more accurate than conventional screen film. The National Cancer Institute agreed to conduct the study. Four device manufacturers submitted data on 10,000 patients each and shared the combined trial costs. The FDA ensured that data were kept confidential among the companies.

The FDA suggests that remedies for the Critical Path include applying new scientific knowledge to improve the medical product development process, stimulating development of robust applied research programs into Critical Path scientific areas to lead to generalized knowledge, strengthening academic bases for Critical Path sciences, and intensifying FDA involvement in Critical Path research and standards development.

The next steps for the FDA include constructing a national Critical Path opportunities list that will include suggestions received from public comments. The FDA intends to make this list available to the public.

Discussion
Forum members engaged in a lively discussion and agreed that large numbers of reconstructive and rehabilitative devices will be used during the next decade.

Identifying Problems
A research scientist stated that some discoveries are not intended to lead to product development nonetheless; these discoveries add to the body of scientific knowledge. Neither academic centers nor the National Institutes of Health (NIH) address the problems of device development infrastructure. As trials are failing later in the development timeline, costs of failures must be factored into the costs of other drug, biologic, device or combination products that become marketable products.

Forum members noted that it would be beneficial to identify tools that could be utilized to predict either safety or efficacy. For instance, the FDA suggested that predictive software that was capable of modeling human effects of design changes to assess device safety or efficacy is urgently needed. A scientist stated that a highly skilled researcher would be needed to write a software program to accomplish that task. Other Forum members suggested that future development should be modeled on existing tools that currently provide functionality.

Training
Forum members agreed that industry provides the most experience in conducting translational research; academia does not generally conduct this type of research. Orthopaedic surgeons asserted that significant funding would have to be allocated for grants in order for this type of research to occur. All participants agreed that industry, academia and the FDA must share information about medical product development.

Grant Mechanisms
Forum members proposed that the FDA should offer grants to fund evidence-based research. Members commented that the Critical Path document is really about generating competent scientific research. All participants agreed that funding such research will cost multiple millions of dollars.

Post Market Surveillance
An industry representative stated that post marketing information for devices is critical to device design improvements. Manufacturers need to assess wear and design modifications in a large population after devices enter the marketplace.

Efficacy
Forum members discussed problems in proving efficacy in premarket approval applications. A manufacturer’s representative questioned what the appropriate endpoints for achieving efficacy were and how to measure and validate them. A surgeon representative suggested that the FDA should mine their data and identify and determine the threshold for failure of certain orthopaedic devices. Participants agreed that this type of tool would indeed be helpful to physicians, industry, and the FDA. Orthopaedic literature generally will not contain this type of information. Members noted the American Academy of Orthopaedic Surgeons (AAOS) joint registry pilot project is intended in part to demonstrate the usefulness of accumulating information to eventually determine early device failure.

Coordination between Federal Agencies
In the Health Affairs January/February 2004 article “Clinical Use of Medical Devices in the Bermuda Triangle,” Kessler, et. al. explain that a simple but potentially effective approach to disseminating information between federal health agencies is to share minutes from advisory panels. Furthermore, they contend that since these documents are in the public domain, developing an email distribution list would facilitate information transfer among those officials with the potential to take action.

Some Forum members noted that there is a lack of coordination between federal agencies including the National Institutes of Health (NIH), the Centers for Medicare and Medicaid Services (CMS), the FDA, and the National Science Foundation (NSF). Further, the agencies are in need of significant improvements to their information services departments.

Science vs. Regulatory
The FDA Critical Path initiative is a scientific initiative however, orthopaedic device manufacturers and orthopaedic surgeons contend that regulatory issues are a major factor in the declining development of novel products. Forum members suggested that it was impossible to decouple scientific and regulatory considerations in the context of the Critical Path initiative.

An orthopaedic surgeon commented that the risk/benefit ratio is different in orthopaedics than in other medical specialties, for example, cardiology. Neither orthopaedic stakeholders nor society has an assessment for how much risk is worth what benefit.

Forum members continued their discussion about the Innovation/Stagnation FDA white paper. A research scientist admitted some frustration that more policy was not changed and encouraged the Forum to define projects that could be accommodated within the FDA framework and to also define projects where substantive change is warranted. The latter projects may require a legislative solution.

Guidance Documents
Forum members acknowledged that FDA guidance documents are important in bringing new technologies to the U.S. marketplace. However, the recent development of the Clinical Trial Design for Hip Replacement Systems draft document proved to be time consuming. Forum members suggested a prioritization of future guidance documents. A scientist asked that the prioritization be adaptable to accommodate new products or orthopaedic device reclassifications.

A manufacturer’s representative suggested that it would be beneficial to draft a guidance document that precedes clinical usage. For instance, a guidance document should be initiated on tissue engineered medical products or combination products. Tissue engineered products are currently being used in countries beyond the U.S. Furthermore, virtually all U.S. orthopaedic companies are developing a product that includes some type of biological material. The future development of tissue engineered synthetic structures is widely anticipated.

Standards Development
The standards consultant assured the Forum that the tissue engineered medical products standards division (TEMPS) of the American Society for Testing and Materials International (ASTM) had already prioritized tissue standards. Forum members acknowledged that International Standards Organization (ISO) standards attempt to address performance standards. Nonetheless, they are generally of the lowest common denominator and are not generally useful to U.S. companies. A manufacturer’s representative stated that companies are concerned about the ramifications of setting performance standards for devices due to the liability aspects of device failure.

Educational Issues
Forum members stressed the need for education initiatives that would target groups of affiliated stakeholders. Specifically, members asserted that the FDA review staff, AAOS fellowship, and Forum members would be well served to tailor activities to address emerging educational issues.

The FDA continues to experience turnover in their review staff. The Forum will continue to produce educational symposia to address important orthopaedic topics relevant to the review of orthopaedic products.

AAOS and Orthopaedic Research and Education Foundation (OREF) representatives explained that surgeons are eager for information on how to bring products to market. They acknowledged that products would probably enter the U.S. marketplace more quickly if companies presented cleaner data. Therefore, there is a need for better training in how to conduct a clinical trial for both the principal investigator and other surgeon investigators. Researchers mentioned that they speak regularly at the AAOS sponsored clinical trials course. One surgeon suggested that the AAOS present an instructional course lecture at the annual meeting. Surgeons questioned the possibility of creating an OREF regulatory fellowship.

The Forum will work on addressing key educational issues and continue Sunday evening sessions with an invited guest. As many members of the Forum have a long tenure, representatives must work toward mentoring the next representatives appointed to the Forum.

Composition of the Forum
A researcher noted that the assessment of biologicals is a new area to be studied and that interested stakeholders are learning basic science. Forum members discussed that representatives from the Center for Biologics, Evaluation and Research (CBER) and the Centers for Medicaid and Medicare Services (CMS) are requested at every meeting to help with biological and reimbursement issues. Additionally, Forum members suggested that some experts in tissue-engineered products would be useful for future group discussion.

A surgeon suggested that a member of an orthopaedic specialty society should attend the Forum depending on the meeting agenda topics to be discussed. A researcher reminded the group that videoconferencing, computer, and phone conferencing are options if a guest is unable to attend in person.

Standards
The ISO meeting is scheduled for September 13-17, 2004 in Vancouver. U.S. representatives are eager to assess the globalization of medical device standards, particularly since the ASTM organization became an international presence. More countries have been added to the European Union; therefore they have added more votes within the ISO voting structure. A few countries are vying for control within the European Union while other countries oppose these attempts to control. Scandinavian countries typically vote similarly to the U.S. contingent while Australia has not defined an allegiance.

The ISO hip wear testing standard continues to be controversial and will not be used within the U.S. While industry contends that it is not an absolute standard, device manufacturers must provide more documentation and justification for deviating from the standard. Countries in the Asian Pacific officially recognize more ISO standards than ASTM standards. China is the largest growing market in the world presently.

ASTM International will meet in Washington, DC on November 9-12, 2004. The F-04 symposium on Titanium, Niobium, Zirconium and Tantalum for Medical and Surgical Applications promises to be enlightening to participants that believe that metal and plastics are outmoded technologies. Symposium faculty will illustrate new material science development for orthopaedic products. Computer guided surgery continues to progress, and the ASTM agreed to convene a subcommittee solely devoted to robotics and computer assisted surgical devices.

MBK
FDA liaisons commented that the FDA will respond to the Orthopaedic Surgical Manufacturers Association (OSMA) on the mobile bearing knee petition and the hip guidance document. Undoubtedly, revisions will be needed. The FDA staff will assess the public transcript and provide an official response to OSMA.

Forum members are encouraged to begin work on another guidance of their choosing. Composite scores or individual parameters are minor points of contention that can be assessed in the future.

Educational Seminars
Previous Forum-developed FDA educational seminars have been deemed successful. The two past seminars included: spinal implants issues and hip and knee device surgical issues. A FDA liaison will assess if funding can be provided for an educational session in 2004 on biological issues including bone graft substitutes and stem cells.

An AAOS representative suggested that since the AAOS 2005 Annual Meeting will be held in Washington, DC, a large contingent of FDA staff might be able to attend symposia and scientific paper presentations.

Artificial Disc Guidance Document
Participation in the development of the Preclinical and Clinical Trial Design for Cervical and Lumbar Disc Replacement Systems has been on an ad hoc basis. Not all subcommittee members have actively participated but activity on the draft versions has increased lately. The wear testing limits will be reduced and cyclic loading will be assessed.

Forum members noted that study design may have an impact on study success and questioned the guidance’s study design parameters. Ad hoc spine subcommittee members readily admit that little medical literature exists on artificial discs. Forum members suggested that the subcommittee reassess the patient population, goals, and complications. Also suggested was a stated rationale for the inclusion of criteria.

Guidance Document Review
A Forum subcommittee reviewed 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).

The subcommittee will decide on a new FDA guidance document to address prior to the next meeting.

Biologics
The ASTM cartilage standard is currently being balloted. The AAOS Biological Implants committee provided input, and the standard is expected to be approved without much controversy. The proposed standard contains guidance on how to pick an animal model and subsequently what information is needed to proceed with a human trial.

The ASTM osteoinduction document is highly controversial and is not expected to succeed. The lack of a known reference standard with which to measure osteoinductivity of products precludes the TEMPS division from drafting an actual standard.

In May 2004, the Centers for Disease Control and Prevention (CDC) reported four deaths attributable to the transplantation of organs from a rabies-infected donor (Update: Investigation of Rabies Infections in Organ Donor and Transplant Recipients-Alabama, Arkansas, Oklahoma, and Texas. Morbidity and Mortality Weekly Report, CDC; July 9, 2004). Fortunately, musculoskeletal tissues were not harvested from this donor.

Members discussed the possibility of producing a biologics workshop that could be adapted for submission to the journal Clinical Orthopaedic and Related Research (CORR). The Chair of the Forum Biologics subcommittee suggested that it would be appropriate to submit timely biological articles to the AAOS Bulletin and the Journal of the American Academy of Orthopaedic Surgeons (JAAOS).

The Biologics subcommittee distributed a survey to the Forum to gain some perspective on the top three emerging biological issues. Results will be tabulated, and the subcommittee will define projects accordingly.

Reimbursement Issues
A research scientist acknowledged that Advanced Tissue Sciences (ATS), Inc. attributes their company’s demise to a lack of reimbursement for their product. Forum members suggested that tissue engineers address CMS code issues while the product is being developed. A surgeon mentioned that a seminar specifically generated for the CMS staff might be helpful as an educational tool. Another member asserted that it would also be beneficial to educate third party payers. Forum members agreed that more dollars are needed to fund CMS programs. As quality is beginning to be assessed by CMS, it is unknown if emerging technologies will be paid and to what extent. A manufacturer’s representative stated that it is easier to navigate the device approval process in Canada.

Regulatory Issues
Another industry representative explained that companies are not opposed to IDE/PMA studies. Finances must be calculated into their business plan, and regulatory predictability is imperative. Companies relate that more predictive endpoints are needed to prove efficacy and that radiostereometric analysis (RSA) might show demonstrative proof of an acceptable endpoint. Manufacturers contend that regulatory and reimbursement issues are still problematic.

FDA Update
CDRH
Bone cements are being cleared for the treatment of pathological fractures of vertebral bodies due to osteoporosis with a kyphoplasty or vertebroplasty procedure.

The Center for Devices and Radiological Health (CDRH) is preparing the proposal to reclassify spinal cages and preparing the necessary draft special controls guidance. Documents are still in the division but will be sent through the appropriate procedural channels prior to public notice in the Federal Register. PROSTALACTM (prosthesis of antibiotic loaded acrylic cement) was granted an humanitarian device exemption (HDE) in March 2001. The reclassification of bone cements allowed manufacturers to submit 510(k)s instead of a Humanitarian Device Exemption (HDE) or PMAs.

CBER
The pending Good Tissue Practice (GTP) final rule is expected in early 2005. CBER is currently drafting a guidance document on gene therapy.

CBER is seeking input from medical professional organizations, biological product manufacturers, and others with interests in facilitating development of the biological products that CBER regulates. A public workshop on their “Innovation/Stagnation” initiative will be held on October 7, 2004 to provide a forum for stakeholders to discuss opportunities for and potential approaches to the development of innovative scientific knowledge and tools to facilitate development. The workshop will address key technologies and the scientific knowledge needed to contribute to an evaluation of the safety and efficacy of cellular, tissue, and gene therapies, and innovative development processes to manufacture them.

The workshop is part of the FDA-wide initiative, “Innovation/Stagnation: Challenge and Opportunity on the Critical Path to New Medical Products'' launched in March 2004, in response to the recent slowdown in innovative medical therapies submitted to FDA for approval. The FDA has described an urgent need to create the scientific and technological “tools” to modernize the medical product development process--the Critical Path--to make medical product development more predictable and less costly. The AAOS Biological Implants Committee will participate in the workshop.
http://www.fda.gov/cber/meetings/criticalpath100704.htm

Biological Implants Committee
Faculty from the AAOS Biological Implants committee will present a symposium on tissue engineering applications in sports medicine at the AAOS 2005 Annual meeting. Members are attending the Medical Technology Leadership Forum (MTLF) on July 29-30, 2004 on the regulation of combination products. The AAOS will file a comment to the FDA on the mode of action for combination products proposed rule prior to the deadline of August 20, 2004.

Biomedical Engineering Committee
The AAOS Biomedical Engineering committee proposed to the AAOS Council on Research that follow-up evidence on new technologies should be presented at AAOS Annual Meetings. The request was supported by the Council and will be assessed by the Program committee.

At the 2005 AAOS Annual Meeting faculty from the Biomedical Engineering committee will present a symposium on less and minimally invasive total joint replacement, an instructional course lecture on robotics, and scientific exhibits on highly cross linked polyethylenes and the development of standards for computer assisted orthopaedic surgery.

NIH
The National Institutes of Health (NIH) budget for FY 2005 is approximately 28 billion dollars with the National Institute of Arthritis and Skin Diseases (NIAMS) budgeted at 500 million dollars. The NIAMS has funded significant research endeavors over the past five years. Grant applications have increased significantly while approximately 20% of the grant applications are currently receiving funding. Active program announcements include: Precursor Cells in Skeletal Muscle Repair and Hypertrophy, Pathogenesis and Treatment of Inflammatory Muscle Disease, Functional Tissue Engineering of Musculoskeletal Tissues, and Orthopaedic Implant Wear. The NIAMS Advisory Council has selected Dr. Jack Parr as the patient representative.

CMS
The coverage and analysis division at CMS is assessing the efficacy of spinal fusion procedures in the Medicare population. CMS staff members are conducting a meta-review and have met with interested stakeholders. CMS hopes to meet with all interested stakeholders in the future after they have gathered sufficient data.

CMS staff attended the June 2, 2004 FDA Panel meeting for the assessment on the premarket application on the DePuy Charite artificial disc. CMS will hold a meeting to address possible codes for certain procedures, including a code for total joint revision surgeries. A memorandum of understanding is being drafted between the FDA and CMS to share pre-investigational device exemption (IDE) data.

AAOS BOD
Robert H. Haralson III, MD, MBA, an AAOS fellow since 1972, joined the Academy as executive director of medical affairs. The Chairman of the Orthopaedic Device Forum will invite Dr. Haralson to the Forum’s November 2004 meeting.

Capitol Hill Research Lobby Day was deemed successful in 2004 due to the inclusion of 15 orthopaedic patients who visited legislators with their orthopaedic surgeons. The patient representatives will meet in August 2004 at the AAOS headquarters to discuss the feasibility of developing a national orthopaedic patient advocacy organization.

AAOS secured orthopaedic research funding language in the FY2005 Department of Defense Appropriations bill, which passed both the House and Senate and awaits President Bush's signature. The bill, through the Peer Reviewed Medical Research Program (PRMRP), was appropriated for 21 health research topics and encourages funding of $50 million for "orthopaedic extremity trauma research", to be distributed through a grant process. Grant applications are typically due in March of each year. Currently, 80% of war injuries are orthopaedic injuries.

The AAOS and the American Association of Neurological Surgeons (AANS), along with other high-risk medical specialty societies founded the Doctors for Medical Liability Reform (DMLR). The DMLR’s Protect Patients Now initiative seeks to educate and inform patients, physicians, business leaders and legislators about the destructive effects of this to our nation’s healthcare and our national economy. States that are facing serious healthcare and economic crises will be highlighted throughout the initiative. The DMLR website is:
http://www.ProtectPatientsNow.org

The AAOS Board unanimously approved the business and implementation plans for an AAOS Expert Witness Professional Compliance program. Under this program, AAOS fellows and members would be permitted to file complaints against other fellows or members regarding all ethical issues for which the AAOS Board has adopted Professional Principles. Among the first of these minimum-standard principles will be expert witness testimony. The new professional compliance program will give substantial due process to those charged with violating Professional Principles.

OSMA
The OSMA metal on metal task force is active and assessing some first generation orthopaedic devices.

AdvaMed continues to be concerned about the reclassification of total joint replacement devices to Class III medical devices as proposed by the United Kingdom’s Medical Devices Agency and France’s Agence Francaise de Securite Sanitaire des Produits de Sante.

Registry
The American Joint Replacement Registry pilot project has selected Barnes-Jewish hospital in St. Louis, Missouri as the first location to collect data. Sharp Memorial Hospital in San Diego will be the second site. Legal agreements are currently being addressed as well as IRB approval. Public funding will eventually be required for a national effort.