Danica Marinac-Dabic

The International Consortium of Orthopaedic Registries: Overview and Summary

FDA Post-Market Efforts and Interest in Orthopaedics The United States Food and Drug Administration (FDA) Center for Devices and Radiological Health (CDRH) monitors both mandatory and voluntary post-market reporting to identify adverse events and problems associated with medical devices. Although the manufacturers of medical devices are required to report deaths, injuries, and malfunctions directly to the FDA, the device users are required to report these events to the manufacturer and are required to report only deaths to the FDA. Voluntary reporting systems such as the MedWatch program, the MAUDE (Manufacturer and User Facility Device Experience) database, and the MedSun (Medical Product Safety Network) enhanced surveillance network provide nationwide medical device surveillance in the U.S. However, these reporting systems have important weaknesses, such as incomplete, inaccurate, or nonvalidated data, reporting biases related to event severity, concerns that reporting may result in adverse publicity or litigation, and general underreporting of events. Most importantly, denominator data are missing, which makes evaluation of the incidence or prevalence of a safety-related event impossible. The FDA’s interest in orthopaedic device safety and in the development of infrastructure for enhanced safety monitoring is natural and timely; the lack of such safety evidence is particularly troubling for the most commonly used implants. Over 700,000 joint replacements involving implantable devices are conducted annually in the U.S. alone, and the annual volume is projected to increase twofold for hip joint replacements and sevenfold for knee joint replacements, to a total of more than 3 million annually, in just the next twenty years. Moreover, these surgical procedures are expected to become more expensive, with costs tripling in just the next five years. Despite remarkable advancements in orthopaedics, including new devices and improved surgical techniques, the value of many therapeutic devices has not been established in clinical trials or in real-world settings. Several factors contribute to this shortcoming: (1) rapidly changing device technology coupled with an enormous number of devices on the market; (2) the need for large numbers of patients and long-term follow-up to adequately evaluate the primary safety end point, which is longterm device failure or need for revision; and (3) the need for prospective data collection, planning, and substantial funding to evaluate short and long-term patient-reported outcomes, which are the primary effectiveness end points. The poor state of research and the resulting inability to learn about a device’s benefits, its potential harms, and the balance between them hinder decision-making by the FDA and other stakeholders such as the Centers for Medicare & Medicaid Services (CMS) and commercial insurers.

The STS-ACC transcatheter valve therapy national registry: a new partnership and infrastructure for the introduction and surveillance of medical devices and therapies.

The Society of Thoracic Surgeons (STS) and American College of Cardiology (ACC) transcatheter valve therapy (TVT) registry is a novel, national registry for all new TVT devices created through a partnership of the STS and the ACC in close collaboration with the Food and Drug Administration, the Center for Medicare and Medicaid Services, and the Duke Clinical Research Institute. The registry will serve as an objective, comprehensive, and scientifically based resource to improve the quality of patient care, to monitor the safety and effectiveness of TVT devices, to serve as an analytic resource for TVT research, and to enhance communication among key stakeholders.

IDEAL framework for surgical innovation 3: randomised controlled trials in the assessment stage and evaluations in the long term study stage

The complexity of surgical procedures often poses challenges for conducting a rigorous and comprehensive evaluation. This paper considers the final two IDEAL stages of surgical innovation. Surgical randomised controlled trials are often challenging to undertake and require careful consideration of the intervention definition, who should deliver it, and the impact of surgeon and patient preferences. In the long term study stage, better monitoring of surgical procedures is needed, along with improved surveillance of devices.

Association Between Endoscopic vs Open Vein-Graft Harvesting and Mortality, Wound Complications, and Cardiovascular Events in Patients Undergoing CABG Surgery

CONTEXT The safety and durability of endoscopic vein graft harvest in coronary artery bypass graft (CABG) surgery has recently been called into question. OBJECTIVE To compare the long-term outcomes of endoscopic vs open vein-graft harvesting for Medicare patients undergoing CABG surgery in the United States. DESIGN, SETTING, AND PATIENTS An observational study of 235,394 Medicare patients undergoing isolated CABG surgery between 2003 and 2008 at 934 surgical centers participating in the Society of Thoracic Surgeons (STS) national database. The STS records were linked to Medicare files to allow longitudinal assessment (median 3-year follow-up) through December 31, 2008. MAIN OUTCOME MEASURES All-cause mortality. Secondary outcome measures included wound complications and the composite of death, myocardial infarction, and revascularization. RESULTS Based on Medicare Part B coding, 52% of patients received endoscopic vein-graft harvesting during CABG surgery. After propensity score adjustment for clinical characteristics, there were no significant differences between long-term mortality rates (13.2% [12,429 events] vs 13.4% [13,096 events]) and the composite of death, myocardial infarction, and revascularization (19.5% [18,419 events] vs 19.7% [19,232 events]). Time-to-event analysis for those patients receiving endoscopic vs open vein-graft harvesting revealed adjusted hazard ratios [HRs] of 1.00 (95% CI, 0.97-1.04) for mortality and 1.00 (95% CI, 0.98-1.05) for the composite outcome. Endoscopic vein-graft harvesting was associated with lower harvest site wound complications relative to open vein-graft harvesting (3.0% [3654/122,899 events] vs 3.6% [4047/112,495 events]; adjusted HR, 0.83; 95% CI, 0.77-0.89; P < .001). CONCLUSION Among patients undergoing CABG surgery, the use of endoscopic vein-graft harvesting compared with open vein-graft harvesting was not associated with increased mortality.

Automated Surveillance to Detect Postprocedure Safety Signals of Approved Cardiovascular Devices

CONTEXT Ensuring the safety of medical devices challenges current surveillance approaches, which rely heavily on voluntary reporting of adverse events. Automated surveillance of clinical registries may provide early warnings in the postmarket evaluation of medical device safety. OBJECTIVE To determine whether automated safety surveillance of clinical registries using a computerized tool can provide early warnings regarding the safety of new cardiovascular devices. DESIGN, SETTING, AND PATIENTS Prospective propensity-matched cohort analysis of 7 newly introduced cardiovascular devices, using clinical data captured in the Massachusetts implementation of the National Cardiovascular Data Repository CathPCI Registry for all adult patients undergoing percutaneous coronary intervention from April 2003 through September 2007 in Massachusetts. MAIN OUTCOME MEASURE Presence of any safety alert, triggered if the cumulative observed risk for a given device exceeded the upper 95% confidence interval (CI) of comparator control device. Predefined sensitivity analyses assessed robustness of alerts when triggered. RESULTS We evaluated 74,427 consecutive interventional coronary procedures. Three of 21 safety analyses triggered sustained alerts in 2 implantable devices. Patients receiving Taxus Express2 drug-eluting stents experienced a 1.28-fold increased risk of postprocedural myocardial infarction (2.87% vs 2.25%; absolute risk increase, 0.62% [95% CI, 0.25%-0.99%]) and a 1.21-fold increased risk of major adverse cardiac events (4.24% vs 3.50%; absolute increase, 0.74% [95% CI, 0.29%-1.19%]) compared with those receiving alternative drug-eluting stents. Patients receiving Angio-Seal STS vascular closure devices experienced a 1.51-fold increased risk of major vascular complications (1.09% vs 0.72%; absolute increased risk, 0.37% [95% CI, 0.03%-0.71%]) compared with those receiving alternative vascular closure devices. Sensitivity analyses confirmed increased risk following use of the Taxus Express2 stent but not the Angio-Seal STS device. CONCLUSION Automated prospective surveillance of clinical registries is feasible and can identify low-frequency safety signals for new cardiovascular devices.

Comparative assessment of implantable hip devices with different bearing surfaces: systematic appraisal of evidence

Objective To determine comparative safety and effectiveness of combinations of bearing surfaces of hip implants. Design Systematic review of clinical trials, observational studies, and registries. Data sources Medline, Embase, Cochrane Controlled Trials Register, reference lists of articles, annual reports of major registries, summaries of safety and effectiveness for pre-market application and mandated post-market studies at the United States Food and Drug Administration. Study selection Criteria for inclusion were comparative studies in adults reporting information for various combinations of bearings (such as metal on metal and ceramic on ceramic). Data search, abstraction, and analyses were independently performed and confirmed by at least two authors. Qualitative data syntheses were performed. Results There were 3139 patients and 3404 hips enrolled in 18 comparative studies and over 830 000 operations in national registries. The mean age range in the trials was 42-71, and 26-88% were women. Disease specific functional outcomes and general quality of life scores were no different or they favoured patients receiving metal on polyethylene rather than metal on metal in the trials. While one clinical study reported fewer dislocations associated with metal on metal implants, in the three largest national registries there was evidence of higher rates of implant revision associated with metal on metal implants compared with metal on polyethylene. One trial reported fewer revisions with ceramic on ceramic compared with metal on polyethylene implants, but data from national registries did not support this finding. Conclusions There is limited evidence regarding comparative effectiveness of various hip implant bearings. Results do not indicate any advantage for metal on metal or ceramic on ceramic implants compared with traditional metal on polyethylene or ceramic on polyethylene bearings.

A framework for evidence evaluation and methodological issues in implantable device studies.

Implantable medical devices (IMD) are frequently used in interventional medicine. There are a host of complex methodological issues to consider in conducting device studies. A general conceptual framework for evidence evaluation is needed to help investigators conduct comparative studies in this setting. It is known that clinical trials of implants require study design planning and creative execution that are quite different from those in pharmaceutical setting. Important study design issues such as randomization, masking and allocation concealment require unique approaches for each device. In addition, device comparative studies must cope with sources of variability different from pharmaceutical studies. These include operator learning curve effects, hospital-operator-patient interactions, and issues related to device technical characteristics. Observational studies of IMDs are particularly challenging. Selection of comparison groups, adjusting for confounding and addressing learning curve issues needs careful planning. We propose a general framework for IMD evaluation and provide an outline of the methodological issues that require further discussion. We hope this article will inspire and help to inform those interested in advancing comparative safety and effectiveness of IMDs and to plan and pursue future methodological work in this area.

National and International Postmarket Research and Surveillance Implementation: Achievements of the International Consortium of Orthopaedic Registries Initiative*

Nearly every American will be exposed to a medical device during his or her life, and tens of millions of people will be treated with an implantable device. However, regulatory and public health systems in the United States and internationally have critical gaps. The U.S. Food and Drug Administration (FDA) has released a national medical device postmarket surveillance plan1, in which the agency identifies as a main priority the goal of promoting the development of national and international medical device registries for selected products. Another top priority of the FDA is the creation of a unique device identification (UDI) system for medical devices in response to a 2007 federal law2.

Sex and risk of hip implant failure: assessing total hip arthroplasty outcomes in the United States.

IMPORTANCE The role of sex in relationship to implant failure after total hip arthroplasty (THA) is important for patient management and device innovation. OBJECTIVE To evaluate the association of sex with short-term risk of THA revision after adjusting for patient, implant, surgery, surgeon, and hospital confounders. DESIGN AND SETTING A prospective cohort of patients enrolled in a total joint replacement registry from April 1, 2001, through December 31, 2010. PARTICIPANTS Patients undergoing primary, elective, unilateral THA. MAIN OUTCOME MEASURES Failure of THA, defined as revision procedure for (1) any reason, (2) septic reason, or (3) aseptic reason after the index procedure. RESULTS A total of 35,140 THAs with 3.0 years of median follow-up were identified. Women constituted 57.5% of the study sample, and the mean (SD) patient age was 65.7 (11.6) years. A higher proportion of women received 28-mm femoral heads (28.2% vs 13.1%) and had metal on highly cross-linked polyethylene-bearing surfaces (60.6% vs 53.7%) than men. Men had a higher proportion of 36-mm or larger heads (55.4% vs 32.8%) and metal on metal-bearing surfaces (19.4% vs 9.6%). At 5-year follow-up, implant survival was 97.4% (95% CI, 97.2%-97.6%). Device survival for men (97.7%; 95% CI, 97.4%-98.0%) vs women (97.1%; 95% CI, 96.8%-97.4%) was significantly different (P = .01). After adjustments, the hazards ratios for women were 1.29 (95% CI, 1.11-1.51) for all-cause revision, 1.32 (95% CI, 1.10-1.58) for aseptic revision, and 1.17 (95% CI, 0.81-1.68) for septic revision. CONCLUSIONS After considering patient-, surgery-, surgeon-, volume-, and implant-specific risk factors, women had a 29% higher risk of implant failure than men after THA in this community-based sample.

Risk of revision for fixed versus mobile-bearing primary total knee replacements.

BACKGROUND Mobile-bearing total knee arthroplasty prostheses were developed to reduce wear and revision rates; however, these benefits remain unproven. The purposes of this study were to compare the short-term survivorship and to determine risk factors for revision of mobile-bearing and fixed-bearing total knee replacements. METHODS A prospective cohort study of primary total knee arthroplasties performed from 2001 to 2009 was conducted with use of a community total joint replacement registry. Patient characteristics and procedure details were identified. Cox regression models were used. Bearing type was investigated as a risk factor for revision while adjusted for other risk factors such as age, American Society of Anesthesiologists (ASA) score, body mass index, sex, race, diagnosis, bilateral procedures, cruciate-retaining versus posterior-stabilized components, surgical approach, fixation, patellar resurfacing, hospital and surgeon volumes, and fellowship training. RESULTS The study cohort consisted of 47,339 total knee arthroplasties, with 62.6% of the procedures in women. Fixed bearings were used in 41,908 knees (88.5%) and mobile bearings in 4830 (10.2%). Rotating-platform designs were used in all mobile-bearing total knee arthroplasties (3112 had a Rotating-Platform Press-Fit Condylar posterior-stabilized design; 1053, a Low Contact Stress [LCS] design; and 665, a Rotating-Platform Press-Fit Condylar cruciate-retaining design). Patients who received fixed-bearing total knee arthroplasty systems were older (mean age, 68.1 years) than those who received mobile-bearing total knee arthroplasty systems (mean age, 62.2 years); the difference was significant (p < 0.001). Overall, 515 knees (1.1%) were revised for reasons other than infection. The survival rate was 97.8% (95% confidence interval [CI], 97.4% to 98.0%) at 6.7 years. The adjusted risk of aseptic revision for the LCS total knee replacements was 2.01 times (95% CI, 1.41 to 2.86) higher than that for fixed-bearing total knee replacements (p < 0.001).There was no significant revision risk for the other mobile-bearing total knee arthroplasty systems. There was no association with surgeon and hospital case volumes and the risk of revision total knee arthroplasty. CONCLUSIONS Our study suggests the benefit of potential long-term wear reduction with the LCS implant may not be realized in a community-based setting, where a variety of surgical skills, surgical experience, and diverse patient demographic factors may affect early outcomes. LEVEL OF EVIDENCE Therapeutic Level II.