Triangulation of findings from several different study designs is important in the generation of the best broadly applicable and generalisable evidence to guide the delivery of efficacious and cost-effective health-care interventions.
Jonathan Thomas Evens and Michael Richard Whitehouse at the Musculoskeletal Research Unit, Translational Health Sciences, Bristol Medical School, Southmead Hospital in Bristol write in The Lancet that David Beard and colleagues at the Nuffield department of orthopaedics, rheumatology and musculoskeletal sciences, in the Botnar Research Centre at the University of Oxford, report on an impressive randomised controlled trial that compared the outcomes of partial knee replacement (PKR) and total knee replacement (TKR) for treatment of isolated medial compartment osteoarthritis of the knee in 528 patients (42% female, mean age 65·0 years) who had an American Society of Anesthesiologists score of 1 or 2, an intact anterior cruciate ligament, and correctable varus deformity.
In the TOPKAT study, Beard and colleagues employed a useful expertise-based and equipoise-based delivery unit design, which successfully facilitated recruitment after previous studies reported difficulty.
Before this study, data from large longitudinal datasets, such as registries, have reported a much higher cumulative probability of revision after PKR than after TKR, uncertainty regarding differences in patient-related outcomes between groups, and much lower early postoperative mortality with PKR.
However, these studies have been subject to selection bias, and little was known of the relative cost-effectiveness of the two operations. A randomised controlled trial is thus timely and important. TOPKAT shows that both interventions provide a 5-year benefit for patients regarding Oxford Knee Score; no evidence of any difference was found between the groups (mean difference 1·04, 95% CI −0·42 to 2·50; p=0·159), indicating that both interventions were clinically effective.
The trial was not powered to show the magnitude of difference in number of revisions that has previously been suggested by registries.
The widely generalisable data obtained from the National Joint Registry for England, Wales, Northern Ireland, and the Isle of Man, which were recorded in the same location as this study, report 5-year revision rates of 2·65% (95% CI 2·61–2·68) for TKR and 6·11% (5·94–6·29) for PKR.
However, TOPKAT was only powered to detect a difference of more than 7% (which would equate to almost a 300% increase in the number of revisions between the two groups).
The health economics data are a welcome addition to our knowledge base, and they suggest improved cost-effectiveness with PKR. In TOPKAT’s within-trial cost-effectiveness analysis, PKR was found to be more effective (0·240 additional quality-adjusted life-years, 95% CI 0·046 to 0·434) and less expensive (−£910, −1503 to −317) than TKR during the 5 years of follow-up. Whether this trend will be sustained beyond 5 years remains to be seen. As more implants are revised over time, the relative cost-effectiveness could change; thus, we await the long-term results with interest. Beard and colleagues report the difference in cost-effectiveness as being partly due to increased outpatient attendance in the TKR group; however, the reasons for this increased attendance are not reported. Follow-up protocols are an area of interest and debate at present, particularly whether we should be reviewing postoperative arthroplasty patients as frequently as at present, and this trial further highlights the potential cost implications associated with this follow-up.
It is encouraging to see that the trial compared classes of knee replacement, rather than brands, and it is thus more likely to be generalisable. Surgeons undertaking PKR in the study had to be relatively high-volume surgeons (performing more than ten surgeries per annum compared to the national median of five surgeries per annum, with an upper quartile of more than 13 surgeries per annum), which means that the results might not be fully generalisable but instead show what is attainable if surgery is undertaken by sub-specialists.
We note that the same strict requirement for surgical experience far greater than the national median was not a requirement in the TKR group, and that the most frequently used brand of TKR, the LCS, is no longer available.
This valuable study adds strength to previous data, which suggested no difference in clinical outcomes between PKR and TKR.
Although it is underpowered to show the marked differences in number of revisions or mortality shown by larger cohort studies, it adds important new evidence for the evaluation of the relative cost-effectiveness of these different operations in the first 5 years after surgery. In view of the results of the TOPKAT study, we agree that the potential benefits and drawbacks associated with PKR versus TKR should be discussed as part of the informed consent process with patients meeting the inclusion criteria for this trial.
Further studies that use methods such as discrete choice experiments and qualitative methods to explore the lived experience of patients undergoing PKR and TKR could help patients and surgeons in the difficult choice between PKR and TKR in those patients who are suitable to receive either option. In the meantime, Beard and colleagues should be commended for the successful delivery of an important randomised controlled trial in arthroplasty, an area that has previously been notorious for the lack of such evidence and for the challenges of conducting randomised trials.
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 cost-effectiveness 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 cost-effectiveness 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.
David J Beard, Loretta J Davies, Jonathan A Cook, Graeme MacLennan, Andrew Price, Seamus Kent, Jemma Hudson, Andrew Carr, Jose Leal, Helen Campbell, Ray Fitzpatrick, Nigel Arden, David Murray, Marion K Campbell