Melanie Calvert

Reporting of Patient-Reported Outcomes in Randomized Trials: The CONSORT PRO Extension

The CONSORT (Consolidated Standards of Reporting Trials) Statement aims to improve the reporting of randomized controlled trials (RCTs); however, it lacks guidance on the reporting of patient-reported outcomes (PROs), which are often inadequately reported in trials, thus limiting the value of these data. In this article, we describe the development of the CONSORT PRO extension based on the methodological framework for guideline development proposed by the Enhancing the Quality and Transparency of Health Research (EQUATOR) Network. Five CONSORT PRO checklist items are recommended for RCTs in which PROs are primary or important secondary end points. These recommendations urge that the PROs be identified as a primary or secondary outcome in the abstract, that a description of the hypothesis of the PROs and relevant domains be provided (ie, if a multidimensional PRO tool has been used), that evidence of the PRO instruments validity and reliability be provided or cited, that the statistical approaches for dealing with missing data be explicitly stated, and that PRO-specific limitations of study findings and generalizability of results to other populations and clinical practice be discussed. Examples and an updated CONSORT flow diagram with PRO items are provided. It is recommended that the CONSORT PRO guidance supplement the standard CONSORT guidelines for reporting RCTs with PROs as primary or secondary outcomes. Improved reporting of PRO data should facilitate robust interpretation of the results from RCTs and inform patient care.

The impact of chronic heart failure on health-related quality of life data acquired in the baseline phase of the CARE-HF study

To assess the quality of life of patients with heart failure, due to left ventricular dysfunction (NYHA class III or IV), taking optimal medical therapy using baseline quality of life assessments from the CArdiac REsynchronisation in Heart Failure (CARE‐HF) trial, and to evaluate the appropriateness of using the EQ‐5D in patients with heart failure.

Effect of the quality and outcomes framework on diabetes care in the United Kingdom: retrospective cohort study

Objectives To examine the management of diabetes between 2001 and 2007 in the United Kingdom and to assess whether changes in the quality of care reflect existing temporal trends or are a direct result of the implementation of the quality and outcomes framework. Design Retrospective cohort study. Setting 147 general practices (annual list size over 1 million) across the UK. Patients People with type 1 or type 2 diabetes. Main outcome measures Annual prevalence of diabetes and attainment of process and clinical outcomes over the three years before and the three years after the introduction of the quality and outcomes framework. Results Significant improvements in process and intermediate outcome measures were observed during the six year period, with consecutive annual improvements observed before the introduction of incentives. However, the current diagnostic case definition for the quality and outcomes framework does not capture up to two thirds of people with type 1 diabetes and a third of people with type 2 diabetes. After the introduction of the quality and outcomes framework, existing trends of improvement in glycaemic control, cholesterol levels, and blood pressure were attenuated, particularly in people with diabetes who did not meet the case definition of the quality and outcomes framework. The introduction of the quality and outcomes framework did not lead to improvement in the management of patients with type 1 diabetes, nor to a reduction in the number of patients with type 2 diabetes who had HbA1c levels greater than 10%. Introduction of the quality and outcomes framework may have increased the number of patients with type 2 diabetes with HbA1c levels of ≤7.5%; odds ratio 1.05 (95% confidence interval 1.01 to 1.09; P=0.02). Conclusions The management of people with diabetes has improved since the late 1990s, but the impact of the quality and outcomes framework on care is not straightforward; upper thresholds may need to be removed or targets made more challenging if people are to benefit. Many patients in whom care may be suboptimal may not be captured in the quality and outcomes framework assessment.

Cost-effectiveness of cardiac resynchronization therapy: results from the CARE-HF trial

AIMS Whilst the CArdiac REsynchronization in Heart Failure (CARE-HF) trial has shown that cardiac resynchronization therapy (CRT) leads to reduced morbidity and mortality, the cost-effectiveness of this therapy remains uncertain. The aim of this study was to evaluate the incremental cost per quality adjusted life year (QALY) gained and incremental cost per life year gained of CRT plus medical therapy compared to medical therapy alone. METHODS AND RESULTS This prospective analysis based on intention to treat data from all patients enrolled in the CARE-HF trial at 82 clinical centres in 12 European countries. A total of 813 patients with New York Heart Association class III or IV heart failure due to left ventricular systolic dysfunction and cardiac dyssynchrony were randomized to CRT plus medical therapy (n = 409) vs. medical therapy alone (n = 404). During a mean follow-up of 29.4 months CRT was associated with increased costs (4316, 95% CI: 1327-7485), survival (0.10 years, 95% CI: -0.01-0.21), and QALYs (0.22, 95% CI: 0.13-0.32). The incremental cost-effectiveness ratio was 19 319 per QALY gained (95% CI: 5482-45 402) and 43 596 per life-year gained (95% CI: -146 236-223 849). These results were sensitive to the costs of the device, procedure, and hospitalization. CONCLUSION Treatment with CRT appears cost-effective at the notional willingness to pay threshold of 29 400 (20,000 pounds sterlings) per QALY gained.

Patient-reported outcomes in randomized clinical trials: Development of ISOQOL reporting standards

PurposeTo develop expert consensus on a suite of reporting standards for HRQL outcomes of RCTs.MethodsA Task Force of The International Society of Quality of Life Research (ISOQOL) undertook a systematic review of the literature to identify candidate reporting standards for HRQL in RCTs. Subsequently, a web-based survey was circulated to the ISOQOL membership. Respondents were asked to rate candidate standards on a 4-point Likert scale based on their perceived value in reporting studies in which HRQL was a study outcome (primary or secondary). Results were synthesized into draft reporting guidelines, which were further reviewed by the membership to inform the final guidance.ResultsForty-six existing candidate standards for reporting HRQL results in RCTs were synthesized to produce a 40 item survey that was completed electronically by 161 respondents. The majority of respondents rated all 40 items to be either ‘essential’ or ‘desirable’ when HRQL was a primary RCT outcome. Ratings changed when HRQL was a secondary study outcome. Feedback on the survey findings resulted in the Task Force generalizing the guidance to include patient-reported outcomes (PROs). The final guidance, which recommends standards for use in reporting PROs generally, and more specifically, for PROs identified as primary study outcomes, was approved by the ISOQOL Board of Directors.ConclusionsISOQOL has developed a suite of recommended standards for reporting PRO results of RCTs. Improved reporting of PROs will enable accurate interpretation of evidence to inform patient choice, aid clinical decision making, and inform health policy.

Impact of wound edge protection devices on surgical site infection after laparotomy: multicentre randomised controlled trial (ROSSINI Trial).

Objective To determine the clinical effectiveness of wound edge protection devices in reducing surgical site infection after abdominal surgery. Design Multicentre observer blinded randomised controlled trial. Participants Patients undergoing laparotomy at 21 UK hospitals. Interventions Standard care or the use of a wound edge protection device during surgery. Main outcome measures Surgical site infection within 30 days of surgery, assessed by blinded clinicians at seven and 30 days and by patient’s self report for the intervening period. Secondary outcomes included quality of life, duration of stay in hospital, and the effect of characteristics of the patient and operation on the efficacy of the device. Results 760 patients were enrolled with 382 patients assigned to the device group and 378 to the control group. Six patients in the device group and five in the control group did not undergo laparotomy. Fourteen patients, seven in each group, were lost to follow-up. A total of 184 patients experienced surgical site infection within 30 days of surgery, 91/369 (24.7%) in the device group and 93/366 (25.4%) in the control group (odds ratio 0.97, 95% confidence interval 0.69 to 1.36; P=0.85). This lack of benefit was consistent across wound assessments performed by clinicians and those reported by patients and across all secondary outcomes. In the secondary analyses no subgroup could be identified in which there was evidence of clinical benefit associated with use of the device. Conclusions Wound edge protection devices do not reduce the rate of surgical site infection in patients undergoing laparotomy, and therefore their routine use for this role cannot be recommended. Trial registration Current Controlled Trials ISRCTN 40402832

The Heart Failure Revascularisation Trial (HEART)

Revascularization is frequently advocated to improve ventricular function and prognosis for patients with heart failure due to coronary artery disease, especially when there is evidence of extensive myocardial viability.

Effects of cardiac resynchronization therapy on long-term quality of life: An analysis from the CArdiac Resynchronisation-Heart Failure (CARE-HF) study

BACKGROUND Cardiac resynchronization therapy (CRT) improves quality of life (QoL) when measured 3 to 6 months after implantation, but whether these effects are sustained is unknown. The CArdiac Resynchronisation-Heart Failure study is the only long-term randomized trial of CRT with repeated measures of QoL. METHODS Quality of life was measured at baseline and 3 months using generic European Quality of Life-5 Dimensions and disease-specific (Minnesota Living with Heart Failure) questionnaires and at 18 months and study-end using the latter instrument. Median follow-up was 29.6 (interquartile range 23.6-34.6) months. RESULTS At baseline, patients had a substantially impaired QoL (mean European Quality of Life-5 Dimensions score 0.60, 95% confidence interval [CI] 0.58-0.62) compared to an age-matched general population (0.78, 95% CI 0.76-0.80). Quality of life improved to a greater extent in patients assigned to CRT at each time point (P < .0001). By 18 months, the mean difference in disease-specific QoL score was 10.7 (95% CI 7.6-13.8) in favor of CRT, mostly due to improved physical functioning. Differences were sustained thereafter. Quality-adjusted life-years at 18 months increased by 0.13 (95% CI 0.07-0.182) and by 0.23 (95% CI 0.13-0.33) at study-end (both P < .0001). Little heterogeneity of effect across subgroups was observed. CONCLUSION Cardiac resynchronization therapy improves long-term QoL and survival in patients with moderate to severe heart failure. The effects appear sustained, and therefore, the gain in quality-adjusted life years with CRT should be even greater during longer term follow-up.

Glucose-Insulin-Potassium Reduces the Incidence of Low Cardiac Output Episodes After Aortic Valve Replacement for Aortic Stenosis in Patients With Left Ventricular Hypertrophy Results From the Hypertrophy, Insulin, Glucose, and Electrolytes (HINGE) Trial

Background— Patients undergoing aortic valve replacement for critical aortic stenosis often have significant left ventricular hypertrophy. Left ventricular hypertrophy has been identified as an independent predictor of poor outcome after aortic valve replacement as a result of a combination of maladaptive myocardial changes and inadequate myocardial protection at the time of surgery. Glucose-insulin-potassium (GIK) is a potentially useful adjunct to myocardial protection. This study was designed to evaluate the effects of GIK infusion in patients undergoing aortic valve replacement surgery. Methods and Results— Patients undergoing aortic valve replacement for aortic stenosis with evidence of left ventricular hypertrophy were randomly assigned to GIK or placebo. The trial was double-blind and conducted at a single center. The primary outcome was the incidence of low cardiac output syndrome. Left ventricular biopsies were analyzed to assess changes in 5′ adenosine monophosphate–activated protein kinase (AMPK), Akt phosphorylation, and protein O-linked &bgr;-N-acetylglucosamination (O-GlcNAcylation). Over a 4-year period, 217 patients were randomized (107 control, 110 GIK). GIK treatment was associated with a significant reduction in the incidence of low cardiac output state (odds ratio, 0.22; 95% confidence interval, 0.10 to 0.47; P=0.0001) and a significant reduction in inotrope use 6 to 12 hours postoperatively (odds ratio, 0.30; 95% confidence interval, 0.15 to 0.60; P=0.0007). These changes were associated with a substantial increase in AMPK and Akt phosphorylation and a significant increase in the O-GlcNAcylation of selected protein bands. Conclusions— Perioperative treatment with GIK was associated with a significant reduction in the incidence of low cardiac output state and the need for inotropic support. This benefit was associated with increased signaling protein phosphorylation and O-GlcNAcylation. Multicenter studies and late follow-up will determine whether routine use of GIK improves patient prognosis. Clinical Trial Registration— URL: http://www.controlled-trials.com. Reference number: ISRCTN 05758301.

Prevalence of ECG abnormalities in an international survey of patients with suspected or confirmed heart failure at death or discharge

Most patients suspected of having heart failure (HF) will get a 12‐lead electrocardiogram (ECG) but its utility for excluding HF or assisting in its management has rarely been investigated.