ORCID Profile
0000-0001-5940-1464
Current Organisation
University of Oxford
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Publisher: National Institute for Health and Care Research
Date: 11-2021
DOI: 10.3310/HTA25660
Abstract: Although routine NHS data potentially include all patients, confounding limits their use for causal inference. Methods to minimise confounding in observational studies of implantable devices are required to enable the evaluation of patients with severe systemic morbidity who are excluded from many randomised controlled trials. Stage 1 – replicate the Total or Partial Knee Arthroplasty Trial (TOPKAT), a surgical randomised controlled trial comparing unicompartmental knee replacement with total knee replacement using propensity score and instrumental variable methods. Stage 2 – compare the risk benefits and cost-effectiveness of unicompartmental knee replacement with total knee replacement surgery in patients with severe systemic morbidity who would have been ineligible for TOPKAT using the validated methods from stage 1. This was a cohort study. Data were obtained from the National Joint Registry database and linked to hospital inpatient (Hospital Episode Statistics) and patient-reported outcome data. Stage 1 – people undergoing unicompartmental knee replacement surgery or total knee replacement surgery who met the TOPKAT eligibility criteria. Stage 2 – participants with an American Society of Anesthesiologists grade of ≥ 3. The patients were exposed to either unicompartmental knee replacement surgery or total knee replacement surgery. The primary outcome measure was the postoperative Oxford Knee Score. The secondary outcome measures were 90-day postoperative complications (venous thromboembolism, myocardial infarction and prosthetic joint infection) and 5-year revision risk and mortality. The main outcome measures for the health economic analysis were health-related quality of life (EuroQol-5 Dimensions) and NHS hospital costs. In stage 1, propensity score stratification and inverse probability weighting replicated the results of TOPKAT. Propensity score adjustment, propensity score matching and instrumental variables did not. Stage 2 included 2256 unicompartmental knee replacement patients and 57,682 total knee replacement patients who had severe comorbidities, of whom 145 and 23,344 had linked Oxford Knee Scores, respectively. A statistically significant but clinically irrelevant difference favouring unicompartmental knee replacement was observed, with a mean postoperative Oxford Knee Score difference of 2 points using propensity score stratification no significant difference was observed using inverse probability weighting. Unicompartmental knee replacement more than halved the risk of venous thromboembolism [relative risk 0.33 (95% confidence interval 0.15 to 0.74) using propensity score stratification relative risk 0.39 (95% confidence interval 0.16 to 0.96) using inverse probability weighting]. Unicompartmental knee replacement was not associated with myocardial infarction or prosthetic joint infection using either method. In the long term, unicompartmental knee replacement had double the revision risk of total knee replacement [hazard ratio 2.70 (95% confidence interval 2.15 to 3.38) using propensity score stratification hazard ratio 2.60 (95% confidence interval 1.94 to 3.47) using inverse probability weighting], but half of the mortality [hazard ratio 0.52 (95% confidence interval 0.36 to 0.74) using propensity score stratification insignificant effect using inverse probability weighting]. Unicompartmental knee replacement had lower costs and higher quality-adjusted life-year gains than total knee replacement for stage 2 participants. Although some propensity score methods successfully replicated TOPKAT, unresolved confounding may have affected stage 2. Missing Oxford Knee Scores may have led to information bias. Propensity score stratification and inverse probability weighting successfully replicated TOPKAT, implying that some (but not all) propensity score methods can be used to evaluate surgical innovations and implantable medical devices using routine NHS data. Unicompartmental knee replacement was safer and more cost-effective than total knee replacement for patients with severe comorbidity and should be considered the first option for suitable patients. Further research is required to understand the performance of propensity score methods for evaluating surgical innovations and implantable devices. This trial is registered as EUPAS17435. This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment Vol. 25, No. 66. See the NIHR Journals Library website for further project information.
Publisher: Wiley
Date: 16-08-2019
DOI: 10.1002/JOR.24423
Publisher: National Institute for Health and Care Research
Date: 09-2021
DOI: 10.3310/HTA25530
Abstract: The use of placebo comparisons for randomised trials assessing the efficacy of surgical interventions is increasingly being considered. However, a placebo control is a complex type of comparison group in the surgical setting and, although powerful, presents many challenges. To provide a summary of knowledge on placebo controls in surgical trials and to summarise any recommendations for designers, evaluators and funders of placebo-controlled surgical trials. To carry out a state-of-the-art workshop and produce a corresponding report involving key stakeholders throughout. A workshop to discuss and summarise the existing knowledge and to develop the new guidelines. To assess what a placebo control entails and to assess the understanding of this tool in the context of surgery is considered, along with when placebo controls in surgery are acceptable (and when they are desirable). We have considered ethics arguments and regulatory requirements, how a placebo control should be designed, how to identify and mitigate risk for participants in these trials, and how such trials should be carried out and interpreted. The use of placebo controls is justified in randomised controlled trials of surgical interventions provided that there is a strong scientific and ethics rationale. Surgical placebos might be most appropriate when there is poor evidence for the efficacy of the procedure and a justified concern that results of a trial would be associated with a high risk of bias, particularly because of the placebo effect. The use of placebo controls is justified in randomised controlled trials of surgical interventions provided that there is a strong scientific and ethics rationale. Feasibility work is recommended to optimise the design and implementation of randomised controlled trials. An outline for best practice was produced in the form of the Applying Surgical Placebo in Randomised Evaluations (ASPIRE) guidelines for those considering the use of a placebo control in a surgical randomised controlled trial. Although the workshop participants involved international members, the majority of participants were from the UK. Therefore, although every attempt was made to make the recommendations applicable to all health systems, the guidelines may, unconsciously, be particularly applicable to clinical practice in the UK NHS. Future work should evaluate the use of the ASPIRE guidelines in making decisions about the use of a placebo-controlled surgical trial. In addition, further work is required on the appropriate nomenclature to adopt in this space. Funded by the Medical Research Council UK and the National Institute for Health Research as part of the Medical Research Council–National Institute for Health Research Methodology Research programme.
Publisher: Cold Spring Harbor Laboratory
Date: 12-11-2021
DOI: 10.1101/2021.11.10.21266128
Abstract: To examine temporal trends in incidence of arthroscopic subacromial decompression (ASAD) surgery internationally during conduct and after publication of placebo controlled trials finding no evidence of meaningful benefit of ASAD for shoulder impingement. Observational study of incidence rates. Large routinely collected datasets were used: outpatient data from Belgium and UK, and insurance claims and outpatient data from US. UK data were from Clinical Practice Research Datalink and Belgium and US data were from IQVIA. US and UK data spanned 2005 – 2019 and Belgium data 2011 – 2019. Patients were eligible for inclusion in the study if they had at least one visit recorded in the database in a given year and cases were defined as patients undergoing ASAD for the first time in their records in a given year. We calculated incidence of ASAD over time, overall and stratified by age and sex. Characteristics of patients undergoing ASAD were also assessed over time. UK incidence has fallen since a peak of 4.7 per 10,000 person years in 2011 (when the CSAW trial began) to 1.8 in 2019. US incidence shows no clear pattern and remains consistently higher than the UK, at 11.5 per 100,000 person years in 2019. Changes in incidence patterns were similar across different age groups and sexes. The number of cases in Belgium was too small for meaningful conclusions. We found ASAD rates have fallen in the UK during conduct and after publication of two large surgical RCTs from the UK and Finland that questioned the effectiveness of ASAD for shoulder impingement. A similar impact on clinical practice has not been seen in US. Further work to understand the barriers or concerns preventing international uptake of high quality evidence into clinical practice is needed. This is the most comprehensive study of ASAD incidence we are aware of. Routinely collected datasets were used to assess proportions of the patients undergoing this procedure in several countries Standardised case definitions were used across databases to increase comparability of findings Temporal changes in database coverage and quality of reporting can influence findings. The observed variation in ASAD incidence may not be entirely attributable to changes in ASAD surgery rates.
Publisher: BMJ
Date: 09-2022
DOI: 10.1136/BMJOPEN-2021-059175
Abstract: To define the population prevalence of rotator cuff tears and test their association with pain and function loss determine if severity symptom correlates with tear stage severity, and quantify the impact of symptomatic rotator cuff tears on primary healthcare services in a general population cohort of women. Cross-sectional observational study. In iduals were part of the Chingford 1000 Women cohort, a 20-year-old longitudinal population study comprising 1003 women aged between 64 and 87, and representative of the population of the UK. Rotator cuff pathology prevalence on ultrasound, shoulder symptoms using the Oxford Shoulder Score and resultant number of general practitioner (GP) consultations. The population prevalence of full-thickness tears was 22.2%, which increased with age (p=0.004) and whether it was the dominant arm (Relative Risk 1.64, OR 1.58, 95% CI 1.07 to 2.33, p=0.021). Although 48.4% of full-thickness tears were asymptomatic, there was an association between rotator cuff tears and patient-reported symptoms. In iduals with at least one full-thickness tear were 1.97 times more likely than those with bilateral normal tendons (OR 3.53, 95% CI 2.00 to 5.61, p .001) to have symptoms. Severity of symptoms was not related to the severity of the pathology until tears are .5 cm (p=0.009). In the cohort, 8.9% had seen their GP with shoulder pain and a full-thickness rotator cuff tear, 18.8% with shoulder pain and an abnormality and 29.3% with shoulder pain. Rotator cuff tears are common, and primary care services are heavily impacted. As 50% of tears remain asymptomatic, future research may investigate the cause of pain and whether different treatment modalities, aside from addressing the pathology, need further investigation.
Publisher: BMJ
Date: 07-2023
DOI: 10.1136/BMJOPEN-2023-071908
Abstract: To investigate the effect of age-related rotator cuff tears on shoulder strength in a general population cohort. Cross sectional observational study. This study was set in an outpatient clinic setting in Chingford, North East London, and was a component of the 20 year visit of the Chingford 1000 women cohort. In iduals were part of the Chingford 1000 women cohort, a 20-year-old longitudinal population study. This cohort has been extensively characterised as representative of the population of the UK. At the 20 year visit, 446 attended for shoulder assessment and were aged between 64 and 87. Isometric shoulder abduction strength measured using a Nottingham Mecmesin Myometer and the presence of rotator cuff pathology, determined via ultrasound examination (GE voluson i portable ultrasound machine with a 10-16MHz linear probe). Shoulders were classified into normal, abnormal tendon artial tear, full-thickness tears ( and ≤2.5 cm) and full-thickness tears ( .5 cm). Symptoms were defined using the Oxford Shoulder Score, where an abnormal score was defined as symptomatic. 446 women (891 shoulders) aged 71 (range 65–84) were included in the study. Age, the presence of pain and the non-dominant arm were demonstrated to reduce strength. Rotator cuff tears and pathology had no isolated effect on shoulder strength in those aged under 70. However, in the over 70s full-thickness tears and ≤2.5 cm, and .5 cm had mean reductions of 6.3 and 12.7 N, respectively (p .001). Rotator cuff tears of all sizes in those aged under 70 were not associated with a loss of shoulder strength. In those aged over 70, strength was reduced by 30% with small and 40% with large full thickness tears. Loss in strength was associated a loss of ability to perform activities of daily living but only for large tears.
Publisher: National Institute for Health and Care Research
Date: 04-2020
DOI: 10.3310/HTA24200
Abstract: Late-stage medial compartment knee osteoarthritis can be treated using total knee replacement or partial (unicompartmental) knee replacement. There is high variation in treatment choice and insufficient evidence to guide selection. To assess the clinical effectiveness and cost-effectiveness of partial knee replacement compared with total knee replacement in patients with medial compartment knee osteoarthritis. The findings are intended to guide surgical decision-making for patients, surgeons and health-care providers. This was a randomised, multicentre, pragmatic comparative effectiveness trial that included an expertise component. The target s le size was 500 patients. A web-based randomisation system was used to allocate treatments. Twenty-seven NHS hospitals (68 surgeons). Patients with medial compartment knee osteoarthritis. The trial compared the overall management strategy of partial knee replacement treatment with total knee replacement treatment. No specified brand or subtype of implant was investigated. The Oxford Knee Score at 5 years was the primary end point. Secondary outcomes included activity scores, global health measures, transition items, patient satisfaction (Lund Score) and complications (including reoperation, revision and composite ‘failure’ – defined by minimal Oxford Knee Score improvement and/or reoperation). Cost-effectiveness was also assessed. A total of 528 patients were randomised (partial knee replacement, n = 264 total knee replacement, n = 264). The follow-up primary outcome response rate at 5 years was 88% and both operations had good outcomes. There was no significant difference between groups in mean Oxford Knee Score at 5 years (difference 1.04, 95% confidence interval –0.42 to 2.50). An area under the curve analysis of the Oxford Knee Score at 5 years showed benefit in favour of partial knee replacement over total knee replacement, but the difference was within the minimal clinically important difference [mean 36.6 (standard deviation 8.3) ( n = 233), mean 35.1 (standard deviation 9.1) ( n = 231), respectively]. Secondary outcome measures showed consistent patterns of benefit in the direction of partial knee replacement compared with total knee replacement although most differences were small and non-significant. Patient-reported improvement (transition) and reflection (would you have the operation again?) showed statistically significant superiority for partial knee replacement only, but both of these variables could be influenced by the lack of blinding. The frequency of reoperation (including revision) by treatment received was similar for both groups: 22 out of 245 for partial knee replacement and 28 out of 269 for total knee replacement patients. Revision rates at 5 years were 10 out of 245 for partial knee replacement and 8 out of 269 for total knee replacement. There were 28 ‘failures’ of partial knee replacement and 38 ‘failures’ of total knee replacement (as defined by composite outcome). Beyond 1 year, partial knee replacement was cost-effective compared with total knee replacement, being associated with greater health benefits (measured using quality-adjusted life-years) and lower health-care costs, reflecting lower costs of the index surgery and subsequent health-care use. It was not possible to blind patients in this study and there was some non-compliance with the allocated treatment interventions. Surgeons providing partial knee replacement were relatively experienced with the procedure. Both total knee replacement and partial knee replacement are effective, offer similar clinical outcomes and have similar reoperation and complication rates. Some patient-reported measures of treatment approval were significantly higher for partial knee replacement than for total knee replacement. Partial knee replacement was more cost-effective (more effective and cost saving) than total knee replacement at 5 years. Further (10-year) follow-up is in progress to assess the longer-term stability of these findings. Current Controlled Trials ISRCTN03013488 and ClinicalTrials.gov NCT01352247. This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment Vol. 24, No. 20. See the NIHR Journals Library website for further project information.
Publisher: National Institute for Health and Care Research
Date: 06-2019
DOI: 10.3310/HTA23320
Abstract: There is no good evidence to support the use of patient-reported outcome measures (PROMs) in setting preoperative thresholds for referral for hip and knee replacement surgery. Despite this, the practice is widespread in the NHS. Can clinical outcome tools be used to set thresholds for hip or knee replacement? What is the relationship between the choice of threshold and the cost-effectiveness of surgery? A systematic review identified PROMs used to assess patients undergoing hip/knee replacement. Their measurement properties were compared and supplemented by analysis of existing data sets. For each candidate score, we calculated the absolute threshold (a preoperative level above which there is no potential for improvement) and relative thresholds (preoperative levels above which in iduals are less likely to improve than others). Owing to their measurement properties and the availability of data from their current widespread use in the NHS, the Oxford Knee Score (OKS) and Oxford Hip Score (OHS) were selected as the most appropriate scores to use in developing the Arthroplasty Candidacy Help Engine (ACHE) tool. The change in score and the probability of an improvement were then calculated and modelled using preoperative and postoperative OKS/OHSs and PROM scores, thereby creating the ACHE tool. Markov models were used to assess the cost-effectiveness of total hip/knee arthroplasty in the NHS for different preoperative values of OKS/OHSs over a 10-year period. The threshold values were used to model how the ACHE tool may change the number of referrals in a single UK musculoskeletal hub. A user group was established that included patients, members of the public and health-care representatives, to provide stakeholder feedback throughout the research process. From a shortlist of four scores, the OHS and OKS were selected for the ACHE tool based on their measurement properties, calculated preoperative thresholds and cost-effectiveness data. The absolute threshold was 40 for the OHS and 41 for the OKS using the preferred improvement criterion. A range of relative thresholds were calculated based on the relationship between a patient’s preoperative score and their probability of improving after surgery. For ex le, a preoperative OHS of 35 or an OKS of 30 translates to a 75% probability of achieving a good outcome from surgical intervention. The economic evaluation demonstrated that hip and knee arthroplasty cost of £20,000 per quality-adjusted life-year for patients with any preoperative score below the absolute thresholds (40 for the OHS and 41 for the OKS). Arthroplasty was most cost-effective for patients with lower preoperative scores. The ACHE tool supports but does not replace the shared decision-making process required before an in idual decides whether or not to undergo surgery. The OHS and OKS can be used in the ACHE tool to assess an in idual patient’s suitability for hip/knee replacement surgery. The system enables evidence-based and informed threshold setting in accordance with local resources and policies. At a population level, both hip and knee arthroplasty are highly cost-effective right up to the absolute threshold for intervention. Our stakeholder user group felt that the ACHE tool was a useful evidence-based clinical tool to aid referrals and that it should be trialled in NHS clinical practice to establish its feasibility. Future work could include (1) a real-world study of the ACHE tool to determine its acceptability to patients and general practitioners and (2) a study of the role of the ACHE tool in supporting referral decisions. The National Institute for Health Research Health Technology Assessment programme.
Publisher: National Institute for Health and Care Research
Date: 02-2021
DOI: 10.3310/HTA25130
Abstract: A rotator cuff tear is a common, disabling shoulder problem. Symptoms may include pain, weakness, lack of shoulder mobility and sleep disturbance. Many patients require surgery to repair the tear however, there is a high failure rate. There is a need to improve the outcome of rotator cuff surgery, and the use of patch augmentation (on-lay or bridging) to provide support to the healing process and improve patient outcomes holds promise. Patches have been made using different materials (e.g. human/animal skin or tissue and synthetic materials) and processes (e.g. woven or mesh). The aim of the Patch Augmented Rotator Cuff Surgery (PARCS) feasibility study was to determine the design of a definitive randomised controlled trial assessing the clinical effectiveness and cost-effectiveness of a patch to augment surgical repair of the rotator cuff that is both acceptable to stakeholders and feasible. A mixed-methods feasibility study of a randomised controlled trial. MEDLINE, EMBASE and the Cochrane Library databases were searched between April 2006 and August 2018. The project involved six stages: a systematic review of clinical evidence, a survey of the British Elbow and Shoulder Society’s surgical membership, a survey of surgeon triallists, focus groups and interviews with stakeholders, a two-round Delphi study administered via online questionnaires and a 2-day consensus meeting. The various stakeholders (including patients, surgeons and industry representatives) were involved in stages 2–6. The systematic review comprised 52 studies only 15 were comparative and, of these, 11 were observational (search conducted in August 2018). These studies were typically small (median number of participants 26, range 5–152 participants). There was some evidence to support the use of patches, although most comparative studies were at a serious risk of bias. Little to no published clinical evidence was available for a number of patches in clinical use. The membership survey of British Elbow and Shoulder surgeons [105 (21%) responses received] identified a variety of patches in use. Twenty-four surgeons (77%) completed the triallist survey relating to trial design. Four focus groups were conducted, involving 24 stakeholders. Differing views were held on a number of aspects of trial design, including the appropriate patient population (e.g. patient age) to participate. Agreement on the key research questions and the outline of two potential randomised controlled trials were achieved through the Delphi study [29 (67%)] and the consensus meeting that 22 participants attended. The main limitation was that the findings were influenced by the participants, who are not necessarily representative of the views of the relevant stakeholder groups. The need for further clinical studies was clear, particularly given the range and number of different patches available. Randomised comparisons of on-lay patch use for completed rotator cuff repairs and bridging patch use for partial rotator cuff repairs were identified as areas for further research. The value of an observational study to assess safety concerns of patch use was also highlighted. These elements are included in the trial designs proposed in this study. The systematic review is registered as PROSPERO CRD42017057908. This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment Vol. 25, No. 13. See the NIHR Journals Library website for further project information.
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for Andrew Carr.