In Silico Clinical Trials in the Orthopedic Device Industry: From Fantasy to Reality?

The orthopedic device industry relies heavily on clinical evaluation to confirm the safety, performance, and clinical benefits of its implants. Limited sample size often prevents these studies from capturing the full spectrum of patient variability and real-life implant use. The device industry is accustomed to simulating benchtop tests with numerical methods and recent developments now enable virtual "in silico clinical trials" (ISCT). In this article, we describe how the advancement of computer modeling has naturally led to ISCT; outline the potential benefits of ISCT to patients, healthcare systems, manufacturers, and regulators; and identify how hurdles associated with ISCT may be overcome. In particular, we highlight a process for defining the relevant patient risks to address with ISCT, the utility of a versatile software pipeline, the necessity to ensure model credibility, and the goal of limiting regulatory uncertainty. By complementing-not replacing-traditional clinical trials with computational evidence, ISCT provides a viable technical and regulatory strategy for characterizing the full spectrum of patients, clinical conditions, and configurations that are embodied in contemporary orthopedic implant systems.

Using the modified Ponseti method to treat complex clubfoot: Early results.

OBJECTIVES: This study aims to present the results of complex clubfoot patients treated with modified Ponseti method and put forth the warning clinical signs of complex deformities. PATIENTS AND METHODS: A total of 11 patients (10 males, 1 female; mean age 60.1±49.7; range, 2 to 180 days) with 16 complex clubfeet treated with modified Ponseti method were included in this study conducted between January 2016 and June 2019. All the data of the patients were collected prospectively and reviewed retrospectively. Demographic features, clubfoot severity, number of casts, position of each foot before cast removal, ankle dorsiflexion (DF), complications, and additional procedures were noted at all clinical visits. RESULTS: Eleven (11.2%) of 98 patients had complex clubfoot deformity. Six (7.7%) of 78 newly diagnosed patients and five (25%) of 20 referred patients had complex clubfeet. We treated 16 complex clubfeet of 11 patients. The mean follow-up period was 13.3 (range, 10 to 16) months. All deformities were initially corrected using a mean of seven (range, 5 to 8) casts and Achilles tenotomy. Relapses occurred in three (18.75%) patients, but all recovered after recasting. The creases above the heels disappeared in all of the patients, whereas plantar creases persisted on two (12.5%) feet. Pirani scores and DF improved statistically significantly after treatment, and DF improved significantly between tenotomy and the final visit. CONCLUSION: The modified Ponseti method is an effective treatment for complex clubfoot. Classical clinical appearance, treatment-resistant deformities and referred patients should be warning signs for complex clubfoot.

Correlation Between Conditional Approval and Customized Bone Implant Devices.

This report aims to summarize key concerns regarding customized devices and conditional approval during the premarket evaluation of bone implants, and to explore the correlation between them. Based on the experience of approval of the first domestic custom-designed bone implant, we consider the process of gaining conditional approval for urgently-needed medical devices and medical devices for rare diseases, as well as the guidance available for clinical investigation. We also streamlined the scientifically administrative concept of this unique device, from the design and development of premarket technical evaluation to continuous post-market study. The present study found that those two aspects have certain connections, but they are not directly correlated to each other. In contrast to the USA, Canada, Australia and the EU, where regulations and guidelines have been established for the use of customized devices, in this regard, China is still it its infancy. Thus, there is considerable potential for China to develop and perfect the policies relating to customized devices and to develop relevant strategies to ensure their efficacy with the aid of conditional approval. Appropriate scientific conditional approval for mass production of individualized anatomy-matching bone implants could become a valuable approach for precision medicine.

Comparing the Efficacy of Methods for Immobilizing the Cervical Spine.

STUDY DESIGN: This was a prospective simulator study with 16 healthy male subjects. OBJECTIVE: The aim of this study was to compare the relative efficacy of immobilization systems in limiting involuntary movements of the cervical spine using a dynamic simulation model. SUMMARY OF BACKGROUND DATA: Relatively few studies have tested the efficacy of immobilization methods for limiting involuntary cervical movement, and only one of these studies used a dynamic simulation system to do so. METHODS: Immobilization configurations tested were cot alone, cot with cervical collar, long spine board (LSB) with cervical collar and head blocks, and vacuum mattress (VM) with cervical collar. A motion platform reproduced shocks and vibrations from ambulance and helicopter field rides, as well as more severe shocks and vibrations that might be encountered on rougher terrain and in inclement weather (designated as an "augmented" ride). Motion capture technology quantitated involuntary cervical rotation, flexion/extension, and lateral bend. The mean and 95% confidence interval of the mean were calculated for the root mean square of angular changes from the starting position and for the maximum range of motion. RESULTS: All configurations tested decreased cervical rotation and flexion/extension relative to the cot alone. However, the LSB and VM were significantly more effective in decreasing cervical rotation than the cervical collar, and the LSB decreased rotation more than the VM in augmented rides. The LSB and VM, but not the cervical collar, significantly limited cervical lateral bend relative to the cot alone. CONCLUSION: Under the study conditions, the LSB and the VM were more effective in limiting cervical movement than the cervical collar. Under some conditions, the LSB decreased repetitive and acute movements more than the VM. Further studies using simulation and other approaches will be essential for determining the safest, most effective configuration should providers choose to immobilize patients with suspected spinal injuries. LEVEL OF EVIDENCE: 3.

Decreasing an Offloading Device's Size and Offsetting Its Imposed Limb-Length Discrepancy Lead to Improved Comfort and Gait.

OBJECTIVE: Patient adherence is a challenge in offloading diabetic foot ulcers (DFUs) with removable cast walkers (RCWs). The size and weight of an RCW, changes to gait, and imposed limb-length discrepancies may all discourage adherence. This study sought to determine whether RCW size and provision of a contralateral limb lift affected users' comfort and gait. RESEARCH DESIGN AND METHODS: Twenty-five individuals at risk for DFUs completed several 20-m walking trials under five footwear conditions: bilateral standardized shoes, a knee-high RCW with shoe with or without an external shoe lift contralaterally, and an ankle-high RCW with shoe with or without an external shoe lift contralaterally. Perceived comfort ratings were assessed through the use of visual analog scales. Spatial and temporal parameters of gait were captured by an instrumented walkway, and plantar pressure was measured and recorded using pedobarographic insoles. RESULTS: The bilateral shoes condition was reported to be most comfortable; both RCW conditions without the lift were significantly less comfortable (P < 0.01). In contrast to the ankle-high RCW, the knee-high RCW resulted in significantly slower walking (5.6%; P < 0.01) but greater offloading in multiple forefoot regions of the offloaded foot (6.8-8.1%; P < 0.01). Use of the contralateral shoe lift resulted in significantly less variability in walking velocity (52.8%; P < 0.01) and reduced stance time for the offloaded foot (2.6%; P = 0.01), but it also reduced offloading in multiple forefoot regions of the offloaded foot (3.7-6.0%; P < 0.01). CONCLUSIONS: Improved comfort and gait were associated with the ankle-high RCW and contralateral limb lift. Providing this combination to patients with active DFUs may increase offloading adherence and subsequently improve healing.

Spinal devices in the United States-investigational device exemption trials and premarket approval of class III devices.

BACKGROUND CONTEXT: Recently, there has been increased public awareness of regulatory actions by the United States Food and Drug Administration (FDA) on spinal devices. There has also been increased scrutiny of the pivotal clinical trials of these devices. PURPOSE: To investigate the premarket approval (PMA) of class III spinal devices in the United States since the turn of the century. To explore clinically relevant issues that affect the interpretation of investigational device exemption trials. STUDY DESIGN: Literature review. METHODS: From 2000 to 2015, data on PMA applications for spinal devices were obtained from two sources. First, meetings of FDA's Orthopaedic and Rehabilitation Devices Panel were identified from the Federal Register. Second, the FDA database of approved PMA applications was queried. For each device, two authors reviewed all archival data. There was no external source of funding. RESULTS: Twenty-one devices met the study criteria. There were 76.2% that received approval and 47.6% that went to panel. Arthroplasty devices were most common (52.4%), least likely to go to panel (3 of 11), and most likely to be approved after panel (3 of 3). Biologic devices were most likely to go to panel (3 of 3) and least likely to be approved after panel (1 of 3). Before and after 2009, there was no decrease in the number of spinal devices approved. All 21 devices were studied in a pivotal clinical trial. All trials except one were randomized controlled trials, and all trials except one were two-arm noninferiority designs. CONCLUSIONS: There has been no decrease in the number of new FDA-approved class III spinal devices since the turn of the century. The majority of devices have been for cervical arthroplasty. By contrast, biologic devices were most likely to go to panel and least likely to be approved after panel. The pivotal trials for nearly all devices were randomized, two-arm, noninferiority trials.

Market approval processes for new types of spinal devices: challenges and recommendations for improvement.

BACKGROUND: Spinal pathology and related symptoms are among the most common health problems and are associated with high health care costs and productivity losses. Due to the aging population, these costs are further increasing every year. Another important reason for the increasing costs is the market approval of new technologies, such as spinal devices that are usually more expensive than the existing technologies. Previous cases of medical device failure led to concern about possible deficiencies in the market approval process. OBJECTIVE: The objective is to provide an overview of U.S. Food and Drug Administration (FDA) regulation regarding spinal implants to delineate the challenges and opportunities that spine surgery currently faces. METHODS: In this paper, two cases of market entries of spinal devices are presented and evaluated to illustrate these deficiencies. RESULTS: Spinal implant regulation is facing several challenges. New spinal devices should increase patient outcomes and safety at reasonable societal costs. The main challenge is to have a rigorous evaluation before dissemination, while still leaving room for innovative behavior that thrusts the healthcare practice forward. CONCLUSION: We have provided recommendations to enhance spinal implant regulation and improve and ensure the patient's safety and the future of spine surgery.

Taking a Concept to Commercialization: Designing Relevant Tests to Address Safety.

Taking a product from concept to commercialization requires careful navigation of the regulatory pathway through a series of steps: (A) moving the idea through proof of concept and beyond; (B) evaluating new technologies that may provide added value to the idea; (C) designing appropriate test strategies and protocols; and (D) evaluating and mitigating risks. Moving an idea from the napkin stage of development to the final product requires a team effort. When finished, the product rarely resembles the original design, but careful steps throughout the product life cycle ensure that the product meets the vision.

[The introduction of new medical devices]. / De introductie van nieuwe medische implantaten.

Regulation of the introduction of new or improved medical devices is fundamentally different from that of new drugs and is inadequate in its current form. This was recently demonstrated by large-scale problems with medical devices in various specialist fields. Steps have been taken by scientific professional associations, regulating authorities and industry to prevent these problems from happening in the future. However, these steps have not yet been implemented or have not been sufficiently well implemented, and have not been completely coordinated. The practitioner therefore needs to remain extremely critical when using new medical devices.

Risk assessment of accidental exposure of surgeons to blood during orthopedic surgery. Are we safe in surgical gloves?

AIM: To analyze tears in sterile surgical gloves used by surgeons in the operating theatre of the Trauma and Orthopedic Surgery Department, Copernicus Memorial Hospital, Lódz, Poland. MATERIALS AND METHOD: This study analyzes tears in sterile surgical gloves used by surgeons by ICD-9 and ICD-10 codes. 1,404 gloves were collected from 581 surgical procedures. All gloves were tested immediately following surgery using the test method described in Standard EN455-1 (each glove was inflated with 1,000 ± 50 ml of water and observed for leaks for 2-3 min.). RESULTS: Analysis of tears took into consideration the role of medical personnel (operator, first assistant, second assistant) during surgical procedure, the type of procedure according to ICD-9 and ICD-10 codes, and the elective or emergency nature of the procedure. The results of the study show that these factors have a significant influence on the risk of glove tears. Significant differences were observed in tear frequency and tear location depending on the function performed by the surgeon during the procedure. CONCLUSION: The study proved that the role performed by the surgeon during the procedure (operator, first assistant, second assistant) has a significant influence on the risk of glove tearing. The role in the procedure determines exposure to glove tears. Implementing a double gloving procedure in surgical procedures or using single gloves characterized by higher tear resistance should be considered.

Temperature control with internally applied cooling in solid material drilling: an experimental, biomechanical study.

PURPOSE: The purpose of this study was to evaluate the different temperature levels while drilling solid materials and to compare different cooling solutions for possible temperature control. An additional purpose was to develop an internal cooling device which can be connected to routinely used manual drilling devices in trauma surgery. METHODS: Drilling was performed on a straight hip stem implanted in bovine femora without cooling, with externally applied cooling and with a newly developed internal cooling device. Temperature changes were measured by seven thermocouples arranged near the borehole. Additionally, thermographic scans were performed during drilling. RESULTS: Drilling without cooling leads to an immediate increase in temperature to levels of thermal osteonecrosis (over 200 °C). With externally applied cooling temperatures were decreased, but were still up to a tissue damaging 85 °C. Internally applied cooling led to a temperature decrease to tissue-preserving levels during the drilling procedure (24.7 °C). CONCLUSION: Internal cooling with HPC-drillers lowered the measured temperatures to non-tissue damaging temperatures and should avoid structural tissue damage.

Cultura de seguridad clínica en cirugía ortopédica y traumatología. Influencia de una intervención formativa / Patient safety culture in orthopaedics surgery. Influence of a training activities plan

Objetivo: Conocer las características de la cultura de seguridad clínica en cirugía ortopédica y traumatología, valorando la influencia de una intervención formativa en su tendencia evolutiva. Población y metodología: Estudio observacional ecológico con intervención formativa. La población objeto de estudio fueron los profesionales del Servicio de Cirugía Ortopédica y Traumatología del Hospital Clínic Universitario de Barcelona. Se utilizó la versión española del cuestionario HSOPS para valorar la cultura de seguridad clínica. Resultados: El porcentaje de respuestas válidas obtenidas fue superior al 60% en las dos mediciones de la cultura realizadas. Las 12 dimensiones consideradas mejoraron su tendencia. El trabajo en equipo dentro del servicio se identificó como una dimensión de fortaleza del modelo. Conclusiones: La intervención formativa ha consolidado una tendencia favorable. La mejora de la cultura de seguridad clínica requiere tiempo y actuaciones periódicas (AU)

Objective: The purpose of this paper is to measure patient safety culture in orthopaedics surgery and to assess the influence of a training activities plan. Methodology: We performed an ecological observational study with a training intervention. Study population included all professionals of Orthopaedics and Traumatology Service of the Clinic Hospital of Barcelona. We used the Spanish version questionnaire HSOPS in order to evaluate safety culture among staff. Results: The percentage of valid questionnaires obtained was above 60% in the two surveys of patient safety culture. The twelve dimensions considered have improved trend. Teamwork climate inside the unit has been identified as a stronghold dimension. Conclusions: The training intervention developed has consolidate a positive trend. The improvement of the patient safety culture needs time and continual actions (AU)

[Clinical trials investigating the therapeutic benefit of medical devices in orthopaedics and trauma surgery: practice examples plus commentary]. / Studien zum therapeutischen Nutzen von Medizinprodukten in O+U: Kommentierte Praxisbeispiele.

Patients recognise relevant symptoms of the two leading diseases in orthopaedics and trauma surgery: osteoarthritis and fractures. Treatment effects can be demonstrated by patient reported outcomes. Total hip arthroplasty as an example for standard treatment regimen achieves large treatment effects. It is hard to demonstrate an additional benefit against standard treatment while observing ceiling effects. Alternative instruments are needed. Navigated total knee arthroplasty is done for better control of the postoperative axis as well as to reduce the revision burden. The time interval needed to demonstrate the decrease in revision has not yet passed. Additional benefits of total knee navigation have been observed for certain patient populations and for the training of physicians. These benefits have not been investigated so far. Using registries, expert opinions and case series the desired benefit from the use of medical devices can be shown. Safety is one major aspect of innovative medical devices as an additional benefit. The safety paradigm needs intense investigation in the future. The IDEAL Statement provides the clinical researcher with the methodological framework. The METEOR Statement focused on the medical problem and the possible benefit with using innovative medical devices. Within these recommendations a broad number of study types can be employed to demonstrate the benefits for patients.

Material properties of common suture materials in orthopaedic surgery.

Suture materials in orthopaedic surgery are used for closure of wounds, repair of fascia, muscles, tendons, ligaments, joint capsules, and cerclage or tension band of certain fractures. The purpose of this study was to compare the biomechanical properties of eleven commonly used sutures in orthopaedic surgery. Three types of braided non-absorbable and one type of braided absorbable suture material with different calibers (n=77) underwent biomechanical testing for maximum load to failure, strain, and stiffness. All samples were tied by one surgeon with a single SMC (Seoul Medical Center) knot and three square knots. The maximum load to failure and strain were highest for #5 FiberWire and lowest for #0 Ethibond Excel (p<0.001). The stiffness was highest for #5 FiberWire and lowest for #2-0 Vicryl (p<0.001). In all samples, the failure of the suture material occurred at the knot There was no slippage of the knot in any of the samples tested. This data will assist the orthopaedic surgeon in selection and application of appropriate suture materials and calibers to specific tasks.

Comparison of patellar mobility in female adults with and without patellofemoral pain.

STUDY DESIGN: Case control study. OBJECTIVE: To compare the patellar mobility of female adult subjects with and without patellofemoral pain (PFP). BACKGROUND: Although abnormal patellar mobility is believed to be one of the causes of PFP, there is currently no published evidence to support this contention. In part, this lack of evidence is because a reliable clinical measurement method to measure patellar mobility and objective criteria to define abnormal patellar mobility have not been established. METHODS AND MEASURES: The study sample was comprised of 22 females with PFP (PFP group) and 22 females who had no knee pain (control group), matched by age, height, and body mass index to the subjects with PFP. Patellar mobility was measured objectively using a specially designed apparatus. Measurements of lateral and medial patellar displacement, patellar mobility balance (lateral minus medial patellar displacement), lateral patellar mobility index (lateral patellar displacement divided by patellar width), and medial patellar mobility index (medial patellar displacement divided by patellar width) were used. RESULTS: Lateral and medial patellar mobility values were not significantly different between the individuals in the PFP and control groups. When normal patellar mobility was arbitrarily defined as the average mobility +/- 2 SDs, based on the data from the control group, normal lateral patellar displacement was within a range of 7.2 to 17.6 mm and normal medial patellar displacement was within a range of 6.8 to 14.0 mm. The intraclass correlation coefficient for intratester and intertester reliability of lateral and medial patellar displacement measurements varied from 0.80 to 0.97. CONCLUSION: Although there were no significant differences in patellar mobility between females with and without PFP, these measurements give reference information about normal patellar mobility for this group. LEVEL OF EVIDENCE: Diagnosis, level 5.