Developing best practice for post-marketing orthopaedic device surveillance:
There is little evidence on the performance of statistical/epidemiological methods for the risk-benefit comparative assessment of orthopaedic medical devices. Given the recent publication of new regulation requiring post-marketing device surveillance, there is an urgent need for guidance on best practice to conduct such research. We therefore aim to study the performance (bias and power) of different statistical methods for comparative risk-benefit observational studies of orthopaedic devices used for the treatment of bone and joint disease/s.
Setting/Design: We will conduct cohort, case-control and case-only observational studies using routinely collected data as available from national registries (national joint registry), audits (national hip fracture database), and linked NHS electronic medical records (hospital episode statistics and patient reported outcomes PROMs database).
Exposure/s and outcome/s: Exposure of interest will be different surgical approaches and/or orthopaedic devices including the following use cases: 1.partial vs total knee replacement for knee osteoarthritis; and 2.hemi vs total hip arthroplasty for hip fracture.Outcomes will include patient-reported outcomes, 90-day and 1-year complications, mortality, length of stay, and NHS costs.
Simulation studies: Simulated datasets will be created based on clinical parameters obtained from these use cases to test the performance of the proposed methods under different circumstances (unobserved/unresolved confounding, skewed/missing data, rare or long-term outcome/s, and surgeon-related variables).
Statistical analyses: Pharmaco-epidemiological methods including propensity scores, disease risk scores, instrumental variables, and self-controlled case series will be tested in routinely collected data, and compared to findings from ongoing surgical randomised controlled trials (gold standard). ‘Validated’ methods (ie those not departing significantly from findings in the RCT) will then be tested using simulation studies, created based on the parameters observed in the clinical datasets. The proposed methods will be compared in terms of percentage bias and power.
We will create guidance for best methods for observational post-marketing comparative device research. Findings will be reported to regulatory agencies (MHRA, EU regulator/s, FDA) and key stakeholders (orthopaedic device industry, patient groups, scientific societies, etc).
Candidates will become part of a multi-disciplinary team including relevant clinicians (academic orthopaedic surgeons, rheumatologists, and GPs), experienced epidemiologists, statisticians, and surgical clinical trialists. Formal training will be offered as provided by the department (CSM training courses, Real World Epidemiology Summer School) as well as externally (Aarhus Pharmaco-epidemiology summer school). In addition, 1-2 month visiting research fellowships/visits will be discussed with relevant research partners at Aarhus University (Denmark).
- The effect of patient age at intervention on risk of implant revision after total replacement of the hip or knee: a population-based cohort study. Bayliss LE, Culliford D, Monk AP, Glyn-Jones S, Prieto-Alhambra D, Judge A, Cooper C, Carr AJ, Arden NK, Beard DJ, Price AJ. Lancet. 2017 Apr 8;389(10077):1424-1430.
- Risk of hip, subtrochanteric, and femoral shaft fractures among mid and long term users of alendronate: nationwide cohort and nested case-control study. Abrahamsen B, Eiken P, Prieto-Alhambra D, Eastell R. BMJ. 2016 Jun 28;353:i3365.
- Primary hip replacement prostheses and their evidence base: systematic review of literature. Kynaston-Pearson F, Ashmore AM, Malak TT, Rombach I, Taylor A, Beard D, Arden NK, Price A, Prieto-Alhambra D, Judge A, Carr AJ, Glyn-Jones S. BMJ. 2013 Dec 19;347:f6956.
- Mortality rates at 10 years after metal-on-metal hip resurfacing compared with total hip replacement in England: retrospective cohort analysis of hospital episode statistics. Kendal AR, Prieto-Alhambra D, Arden NK, Carr A, Judge A. BMJ. 2013 Nov 27;347:f6549.