The investigation of surrogate markers for post-market surveillance in primary total hip arthroplasty

The recent catastrophe of metal-on-metal Total Hip Arthroplasty devices have highlighted the need for early identification of failing devices newly introduced in the market. New regulations have come into force with an emphasis on pre-market clinical evidence generation, transparency, and post-marketing surveillance. However, there are significant limitations with current surveillance using joint registries due to reliance on measuring revision rate. Revision is a rare and typically long-term outcome therefore requiring a significant number of patients undergoing surgery and extended follow-up to detect those devices that are outliers. Therefore, surrogate markers of subsequent revision rate are sought to ensure failing devices are detected early. The systematic review investigates which available surrogate markers have been validated against the current National Institute for Health and Care Excellence guidelines for an established device. This study found the only validated surrogate marker was implant migration and wear within two-years post-operatively. The only method for measuring wear and migration for both the femoral and acetabular components was Radiostereometric Analysis. However, this has significant limitations in cost, availability, and the failure to universally predict long-term fixation in all devices. Therefore, alternative surrogate markers that are cost-effective are sought. Chapter 3 investigates analgesic and healthcare utilisation within the first post-operative year as potential surrogate markers of subsequent revision rate in primary hip arthroplasty surgery. Survival analysis demonstrated increased risk of revision for each surrogate marker. Patients in the top quintile of NSAID use had a sub-hazard ratio (SHR) of 2.20 [95%CI 1.35-3.59; p=0.002], patients using Tramadol SHR 2.42 [95%CI 1.74-3.35; p Chapter 4 further investigates whether the novel analgesic and healthcare utilisation surrogate markers can identify differences between device bearings. There was no significant difference in revision rate between metal-on-metal and other bearings in the RACat cohort. However, two surrogate markers were able to identify a difference suggesting that analgesic and healthcare utilisation may potentially be able to identify outliers earlier than revision rate alone. The findings suggest the possible use of these surrogate markers as part of a surveillance programme to identify potentially failing devices early, based on routinely collected data from registries and, where available, linked electronic medical records. Such surrogate markers can be easily collected at low cost with no impact on patients and physicians.</p

Primary hip replacement prostheses and their evidence base: systematic review of literature

OBJECTIVE: To determine the extent to which prostheses with no readily available evidence to support their use are being implanted in primary total hip arthroplasty. DESIGN: Systematic review of the literature. DATA SOURCES: The 9th annual report of the National Joint Registry of England and Wales (NJR) was analysed to identify prostheses with an Orthopaedic Data Evaluation Panel rating of "unclassified" or "pre-entry" used in primary total hip arthroplasty in 2011. A systematic review of those prostheses was carried out using PubMed, Cochrane, Embase, OVID, and Google databases. STUDY SELECTION: Prostheses used in primary total hip arthroplasty as published in the NJR's 9th annual report were analysed. Only literature that included the name of the prosthesis was included. Literature yielded in the search results was excluded if it reported animal, non-orthopaedic, non-total hip arthroplasty, or non-device related studies. RESULTS: The systematic review found that 24% (57/235) of all hip replacement implants available to surgeons in the UK have no evidence for their clinical effectiveness. It also shows that 10,617 (7.8%) of the 136,593 components used in primary hip replacements in 2011 were implanted without readily identifiable evidence of clinical effectiveness. These comprised 157 cemented stems (0.5% of 34,655 implanted), 936 (2.8% of 33,367) uncemented stems, 1732 (7.1% of 24,349) cemented cups, and 7577 (17.1% of 44,222) uncemented cups. CONCLUSIONS: This study shows that a considerable proportion of prostheses available to orthopaedic surgeons have no readily available evidence of clinical effectiveness to support their use. Concern exists about the current system of device regulation, and the need for a revised process for introducing new orthopaedic devices is highlighted

Primary hip replacement prostheses and their evidence base: systematic review of literature

OBJECTIVE: To determine the extent to which prostheses with no readily available evidence to support their use are being implanted in primary total hip arthroplasty. DESIGN: Systematic review of the literature. DATA SOURCES: The 9th annual report of the National Joint Registry of England and Wales (NJR) was analysed to identify prostheses with an Orthopaedic Data Evaluation Panel rating of "unclassified" or "pre-entry" used in primary total hip arthroplasty in 2011. A systematic review of those prostheses was carried out using PubMed, Cochrane, Embase, OVID, and Google databases. STUDY SELECTION: Prostheses used in primary total hip arthroplasty as published in the NJR's 9th annual report were analysed. Only literature that included the name of the prosthesis was included. Literature yielded in the search results was excluded if it reported animal, non-orthopaedic, non-total hip arthroplasty, or non-device related studies. RESULTS: The systematic review found that 24% (57/235) of all hip replacement implants available to surgeons in the UK have no evidence for their clinical effectiveness. It also shows that 10,617 (7.8%) of the 136,593 components used in primary hip replacements in 2011 were implanted without readily identifiable evidence of clinical effectiveness. These comprised 157 cemented stems (0.5% of 34,655 implanted), 936 (2.8% of 33,367) uncemented stems, 1732 (7.1% of 24,349) cemented cups, and 7577 (17.1% of 44,222) uncemented cups. CONCLUSIONS: This study shows that a considerable proportion of prostheses available to orthopaedic surgeons have no readily available evidence of clinical effectiveness to support their use. Concern exists about the current system of device regulation, and the need for a revised process for introducing new orthopaedic devices is highlighted

The relationship between polyethylene wear and periprosthetic osteolysis in total hip arthroplasty at 12 years in a randomized controlled trial cohort

Polyethylene acetabular components are common in hip arthroplasty. Highly cross-linked polyethylene (HXLPE) has lower wear than ultra-high molecular weight polyethylene (UHMWPE). Evidence suggests that wear particles induce inflammation causing periprosthetic osteolysis contributing to implant loosening with wear rates of 0.05 mm/y were considered safe. We aimed to compare incidence and volume of periacetabular osteolysis between HXLPE and UHMWPE using computed tomography.Initially, 54 hips in 53 patients were randomized to HXLPE or UHMWPE acetabular liner. At 10 years, 39 hips in 38 patients remained for the radiostereometric analysis' demonstrating significantly lower wear in the HXLPE group. At 12 years, 14 hips in 13 patients were lost to follow-up leaving 25 hips for computed tomography assessment. Images were reconstructed to detect osteolysis and where identified, areas were segmented and volumized.Osteolysis was observed in 8 patients, 7 from the UHMWPE group and only 1 from the HXLPE group (Fisher exact, P = .042). There was no correlation between the amount of polyethylene wear and osteolysis volume; however, the radiostereometric analysis-measured wear rate in patients with osteolysis from both groups was significantly higher than overall average wear rate.This data demonstrates lower incidence of periacetabular osteolysis in the HXLPE group of a small cohort. Although numbers are too low to estimate causation, in the context of lower wear in the HXLPE group, this finding supports the hypothesis that HXLPE may not elevate osteolysis risk, and hence does not suggest that HXLPE wear particles are more biologically active than those generated by earlier generations of polyethylene

The relationship between polyethylene wear and periprosthetic osteolysis in total hip arthroplasty at 12 years in a randomized controlled trial cohort

Polyethylene acetabular components are common in hip arthroplasty. Highly cross-linked polyethylene (HXLPE) has lower wear than ultra-high molecular weight polyethylene (UHMWPE). Evidence suggests that wear particles induce inflammation causing periprosthetic osteolysis contributing to implant loosening with wear rates of 0.05 mm/y were considered safe. We aimed to compare incidence and volume of periacetabular osteolysis between HXLPE and UHMWPE using computed tomography.Initially, 54 hips in 53 patients were randomized to HXLPE or UHMWPE acetabular liner. At 10 years, 39 hips in 38 patients remained for the radiostereometric analysis' demonstrating significantly lower wear in the HXLPE group. At 12 years, 14 hips in 13 patients were lost to follow-up leaving 25 hips for computed tomography assessment. Images were reconstructed to detect osteolysis and where identified, areas were segmented and volumized.Osteolysis was observed in 8 patients, 7 from the UHMWPE group and only 1 from the HXLPE group (Fisher exact, P = .042). There was no correlation between the amount of polyethylene wear and osteolysis volume; however, the radiostereometric analysis-measured wear rate in patients with osteolysis from both groups was significantly higher than overall average wear rate.This data demonstrates lower incidence of periacetabular osteolysis in the HXLPE group of a small cohort. Although numbers are too low to estimate causation, in the context of lower wear in the HXLPE group, this finding supports the hypothesis that HXLPE may not elevate osteolysis risk, and hence does not suggest that HXLPE wear particles are more biologically active than those generated by earlier generations of polyethylene

Primary stability of a short bone-conserving femoral stem: a two-year randomized controlled trial using radiostereometric analysis

Aims The aim of this study was to determine the stability of a new short femoral stem compared with a conventional femoral stem in patients undergoing cementless total hip arthroplasty (THA), in a prospective randomized controlled trial using radiostereometric analysis (RSA). Patients and Methods A total of 53 patients were randomized to receive cementless THA with either a short femoral stem (MiniHip, 26 patients, mean age: 52 years, nine male) or a conventional length femoral stem (MetaFix, 23 patients, mean age: 53 years, 11 male). All patients received the same cementless acetabular component. Two-year follow-up was available on 38 patients. Stability was assessed through migration and dynamically inducible micromotion. Radiographs for RSA were taken postoperatively and at three, six, 12, 18, and 24 months. Results At two years, there was significantly less subsidence (inferior migration) of the short femoral stem (head, 0.26 mm, 95% confidence interval (CI) 0.08 to 0.43, sd 0.38; tip, 0.11 mm, 95% CI -0.08 to 0.31, sd 0.42) compared with the conventional stem (head, 0.62 mm, 95% CI 0.34 to 0.90, sd 0.56, p = 0.02; tip, 0.43 mm, 95% CI 0.21 to 0.65, sd 0.44, p = 0.03). There was no significant difference in dynamically inducible micromotion, rate of complications or functional outcome. Conclusion This study demonstrates that the short femoral stem has a stable and predictable migration. However, longer-term survival analysis still needs to be determined

Primary stability of a short bone-conserving femoral stem: a two-year randomized controlled trial using radiostereometric analysis

Aims The aim of this study was to determine the stability of a new short femoral stem compared with a conventional femoral stem in patients undergoing cementless total hip arthroplasty (THA), in a prospective randomized controlled trial using radiostereometric analysis (RSA). Patients and Methods A total of 53 patients were randomized to receive cementless THA with either a short femoral stem (MiniHip, 26 patients, mean age: 52 years, nine male) or a conventional length femoral stem (MetaFix, 23 patients, mean age: 53 years, 11 male). All patients received the same cementless acetabular component. Two-year follow-up was available on 38 patients. Stability was assessed through migration and dynamically inducible micromotion. Radiographs for RSA were taken postoperatively and at three, six, 12, 18, and 24 months. Results At two years, there was significantly less subsidence (inferior migration) of the short femoral stem (head, 0.26 mm, 95% confidence interval (CI) 0.08 to 0.43, sd 0.38; tip, 0.11 mm, 95% CI -0.08 to 0.31, sd 0.42) compared with the conventional stem (head, 0.62 mm, 95% CI 0.34 to 0.90, sd 0.56, p = 0.02; tip, 0.43 mm, 95% CI 0.21 to 0.65, sd 0.44, p = 0.03). There was no significant difference in dynamically inducible micromotion, rate of complications or functional outcome. Conclusion This study demonstrates that the short femoral stem has a stable and predictable migration. However, longer-term survival analysis still needs to be determined