Background Late-stage isolated medial knee osteoarthritis can be treated with total knee replacement (TKR) or partial knee replacement (PKR). There is high variation in treatment choice and little robust evidence to guide selection. The Total or Partial Knee Arthroplasty Trial (TOPKAT) therefore aims to assess the clinical effectiveness and costeffectiveness of TKR versus PKR in patients with medial compartment osteoarthritis of the knee, and this represents an analysis of the main endpoints at 5 years. Methods Our multicentre, pragmatic randomised controlled trial was done at 27 UK sites. We used a combined expertise-based and equipoise-based approach, in which patients with isolated osteoarthritis of the medial compartment of the knee and who satisfied general requirements for a medial PKR were randomly assigned (1:1) to receive PKR or TKR by surgeons who were either expert in and willing to perform both surgeries or by a surgeon with particular expertise in the allocated procedure. The primary endpoint was the Oxford Knee Score (OKS) 5 years after randomisation in all patients assigned to groups. Health-care costs (in UK 2017 prices) and cost-effectiveness were also assessed. This trial is registered with ISRCTN (ISRCTN03013488) and ClinicalTrials.gov (NCT01352247). Findings Between Jan 18, 2010, and Sept 30, 2013, we assessed 962 patients for their eligibility, of whom 431 (45%) patients were excluded (121 [13%] patients did not meet the inclusion criteria and 310 [32%] patients declined to participate) and 528 (55%) patients were randomly assigned to groups. 94% of participants responded to the follow-up survey 5 years after their operation. At the 5-year follow-up, we found no difference in OKS between groups (mean difference 1•04, 95% CI-0•42 to 2•50; p=0•159). In our within-trial cost-effectiveness analysis, we found that PKR was more effective (0•240 additional quality-adjusted life-years, 95% CI 0•046 to 0•434) and less expensive (-£910, 95% CI-1503 to-317) than TKR during the 5 years of follow-up. This finding was a result of slightly better outcomes, lower costs of surgery, and lower follow-up health-care costs with PKR than TKR. Interpretation Both TKR and PKR are effective, offer similar clinical outcomes, and result in a similar incidence of re-operations and complications. Based on our clinical findings, and results regarding the lower costs and better costeffectiveness with PKR during the 5-year study period, we suggest that PKR should be considered the first choice for patients with late-stage isolated medial compartment osteoarthritis.

Placebo comparisons are increasingly being considered for randomised trials assessing the efficacy of surgical interventions. The aim of this paper is to provide a summary of current knowledge on placebo controls in surgical trials. A placebo control is a complex type of comparison group and, although powerful, presents many challenges in a surgical setting. This review outlines what a placebosurgical control entails and our understanding of the placebo phenomenon in the context of surgery. It considers when placebo-surgical controls are acceptable (and when they are desirable) in terms of ethical arguments and regulatory requirements, how a placebo-surgical control should be designed, how to identify and mitigate risk for participants in placebo surgical trials, how such trials should be conducted and interpreted. Use of placebo control is justified in randomised controlled trials of surgical interventions provided there is a strong scientific and ethical rationale. Surgical placebos may be most appropriate where there is poor evidence on the efficacy of the procedure and a justified concern that results of a trial would be associated with high risk of bias, particularly due to the placebo effect. Feasibility work is recommended to optimise RCT design and conduct. This review forms an outline for best practice and provides guidance, in the form of the ASPIRE (Applying Surgical Placebo in Randomised Evaluations) checklist, for those considering the use of a placebo-control in a surgical randomised controlled trial.