The investigation of surrogate markers for post-market surveillance in primary total hip arthroplasty
Keywords: hip replacement
hip arthroplasty
THA
survival
outcome
surrogate marker

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<0.001], those using atypical analgesics SHR 2.59 [95%CI 1.70-3.95; p<0.001], patients visiting their primary care physician more than four times had a SHR of 2.10 [95%CI 1.29-3.42; p=0.003], patients referred to the Orthopaedic department SHR 1.90 [95%CI 1.16-3.13; p=0.011], and those referred to the Physiotherapy department SHR 2.07 [95%CI 1.29-3.32; p=0.003].
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.