Robert N. Whistance

Developing core outcomes sets: methods for identifying and including patient-reported outcomes (PROs)

BackgroundSynthesis of patient-reported outcome (PRO) data is hindered by the range of available PRO measures (PROMs) composed of multiple scales and single items with differing terminology and content. The use of core outcome sets, an agreed minimum set of outcomes to be measured and reported in all trials of a specific condition, may improve this issue but methods to select core PRO domains from the many available PROMs are lacking. This study examines existing PROMs and describes methods to identify health domains to inform the development of a core outcome set, illustrated with an example.MethodsSystematic literature searches identified validated PROMs from studies evaluating radical treatment for oesophageal cancer. PROM scale/single item names were recorded verbatim and the frequency of similar names/scales documented. PROM contents (scale components/single items) were examined for conceptual meaning by an expert clinician and methodologist and categorised into health domains. A patient advocate independently checked this categorisation.ResultsSearches identified 21 generic and disease-specific PROMs containing 116 scales and 32 single items with 94 different verbatim names. Identical names for scales were repeatedly used (for example, ‘physical function’ in six different measures) and others were similar (overlapping face validity) although component items were not always comparable. Based on methodological, clinical and patient expertise, 606 individual items were categorised into 32 health domains.ConclusionThis study outlines a methodology for identifying candidate PRO domains from existing PROMs to inform a core outcome set to use in clinical trials.

The Inflammatory Response to Miniaturised Extracorporeal Circulation: A Review of the Literature

Conventional cardiopulmonary bypass can trigger a systemic inflammatory response syndrome similar to sepsis. Aetiological factors include surgical trauma, reperfusion injury, and, most importantly, contact of the blood with the synthetic surfaces of the heart-lung machine. Recently, a new cardiopulmonary bypass system, mini-extracorporeal circulation (MECC), has been developed and has shown promising early results in terms of reducing this inflammatory response. It has no venous reservoir, a reduced priming volume, and less blood-synthetic interface. This review focuses on the inflammatory and clinical outcomes of using MECC and compares these to conventional cardio-pulmonary bypass (CCPB). MECC has been shown to reduce postoperative cytokines levels and other markers of inflammation. In addition, MECC reduces organ damage, postoperative complications and the need for blood transfusion. MECC is a safe and viable perfusion option and in certain circumstances it is superior to CCPB.

Systematic review and meta-analysis of audio-visual information aids for informed consent for invasive healthcare procedures in clinical practice

OBJECTIVE To systematically review audio-visual (AV) interventions for promoting informed consent (IC) in clinical practice and to consider the impact of reading age adjustment. METHODS Systematic review of randomized controlled trials (RCTs) comparing AV interventions to standard IC in clinical practice. Outcomes included recall (immediate <1 day; intermediate 1-14 days; late >14 days), satisfaction and anxiety. Data were synthesized using random effects meta-analyses. Comparisons were made between studies that did and did not adjust for participant reading age. RESULTS Of 11,813 abstracts screened, 29 RCTs were eligible (30 intervention arms). Interventions included videos (n=17), computer programs (n=5), electronic presentations (n=3), compact discs (n=3) and websites (n=2). Meta-analysis showed AV interventions improved immediate recall (standardized mean difference [SMD] 0.64, 95% confidence interval [CI] 0.45-0.85). Results for intermediate and late recall were too heterogeneous to synthesize. AV interventions did not consistently affect either satisfaction or anxiety. Adjusting the reading age of interventions improved immediate recall (reading age interventions: adjusted SMD 1.21, 95%CI 0.81-1.61; non-reading age adjusted SMD 0.51, 95%CI 0.36-0.66). CONCLUSION AV interventions, especially those adjusted for participant reading age, improve immediate information recall for IC. Practice implications Wider use of AV aids is justified when obtaining IC in clinical practice.

Core Outcomes for Colorectal Cancer Surgery: A Consensus Study.

Background Colorectal cancer (CRC) is a major cause of worldwide morbidity and mortality. Surgical treatment is common, and there is a great need to improve the delivery of such care. The gold standard for evaluating surgery is within well-designed randomized controlled trials (RCTs); however, the impact of RCTs is diminished by a lack of coordinated outcome measurement and reporting. A solution to these issues is to develop an agreed standard “core” set of outcomes to be measured in all trials to facilitate cross-study comparisons, meta-analysis, and minimize outcome reporting bias. This study defines a core outcome set for CRC surgery. Methods and Findings The scope of this COS includes clinical effectiveness trials of surgical interventions for colorectal cancer. Excluded were nonsurgical oncological interventions. Potential outcomes of importance to patients and professionals were identified through systematic literature reviews and patient interviews. All outcomes were transcribed verbatim and categorized into domains by two independent researchers. This informed a questionnaire survey that asked stakeholders (patients and professionals) from United Kingdom CRC centers to rate the importance of each domain. Respondents were resurveyed following group feedback (Delphi methods). Outcomes rated as less important were discarded after each survey round according to predefined criteria, and remaining outcomes were considered at three consensus meetings; two involving international professionals and a separate one with patients. A modified nominal group technique was used to gain the final consensus. Data sources identified 1,216 outcomes of CRC surgery that informed a 91 domain questionnaire. First round questionnaires were returned from 63 out of 81 (78%) centers, including 90 professionals, and 97 out of 267 (35%) patients. Second round response rates were high for all stakeholders (>80%). Analysis of responses lead to 45 and 23 outcome domains being retained after the first and second surveys, respectively. Consensus meetings generated agreement on a 12 domain COS. This constituted five perioperative outcome domains (including anastomotic leak), four quality of life outcome domains (including fecal urgency and incontinence), and three oncological outcome domains (including long-term survival). Conclusion This study used robust consensus methodology to develop a core outcome set for use in colorectal cancer surgical trials. It is now necessary to validate the use of this set in research practice.

Outcome reporting in bariatric surgery: An in-depth analysis to inform the development of a core outcome set, the BARIACT Study

Outcome reporting in bariatric surgery needs a core outcome set (COS), an agreed minimum set of outcomes reported in all studies of a particular condition. The aim of this study was to summarize outcome reporting in bariatric surgery to inform the development of a COS. Outcomes reported in randomized controlled trials (RCTs) and large non‐randomized studies identified by a systematic review were listed verbatim and categorized into domains, scrutinizing the frequency of outcome reporting and uniformity of definitions. Ninety studies (39 RCTs) identified 1,088 separate outcomes, grouped into nine domains with most (n = 920, 85%) reported only once. The largest outcome domain was ‘surgical complications’, and overall, 42% of outcomes corresponded to a theme of ‘adverse events’. Only a quarter of outcomes were defined, and where provided definitions, which were often contradictory. Percentage of excess weight loss was the main study outcome in 49 studies, but nearly 40% of weight loss outcomes were heterogeneous, thus not comparable. Outcomes of diverse bariatric operations focus largely on adverse events. Reporting is inconsistent and ill‐defined, limiting interpretation and comparison of published studies. Thus, we propose and are developing a COS for the surgical treatment of severe and complex obesity.

Valve-preserving surgery on the bicuspid aortic valve

Valve repair has emerged as an important intervention for the management of bicuspid aortic valve disease. This systematic review aims to assess the safety, efficacy and durability of bicuspid aortic valve repair. Initial searches yielded 682 abstracts, reduced by de-duplication to 370, of which 56 full papers were accessed and 30 met the inclusion criteria. Overall, 163 unique outcomes for bicuspid aortic valve-preserving surgery were reported on 280 occasions. Bicuspid aortic valve-preserving surgery exhibited low operative mortality (0.0-5.2%), excellent 5-year survival (82-100%) and 43-100% 5-year freedom from reoperation. Bicuspid aortic valve repair is safe and efficacious, but concerns regarding its durability necessitate further standardized outcome assessments.

Early and mid-term outcomes of trans-sternal and video-assisted thoracoscopic surgery for thymoma

OBJECTIVES Video-assisted thoracoscopic surgery (VATS) for thymoma has uncertain safety and effectiveness in comparison with trans-sternal resection. This feasibility study compared short- and mid-term outcomes for patients undergoing these two procedures, highlights weaknesses in current research and makes recommendations for long-term technological evaluations in this field. METHODS Consecutive thymoma cases between 2004 and 2010 were identified. Patients were divided into two groups according to surgical approach (Group I trans-sternal; Group II VATS) and comparisons were made between groups. The primary outcome was overall survival. Secondary outcomes included operative morbidity and mortality, hospital stay, recurrence rate and disease-free survival. RESULTS Thirty-nine patients were included (Group I: n = 22 vs Group II: n = 17). There were no differences between groups at baseline for all measured covariates. No deaths occurred within 30 days of surgery. More patients in Group I developed complications (Group I: n = 10 vs Group II: n = 3; P = 0.093), while hospital stay was shorter in Group II (Group I: 6.4 ± 4.6 days vs Group II: 4.4 ± 1.8 days; P = 0.030). Five-year overall survival (Group I: 93.8 ± 6.1% vs Group II: 83.3 ± 11.2%; P = 0.425), 5-year disease-free survival (Group I: 71.0 ± 15.3% vs Group II: 83.3 ± 11.2%; P = 0.827) and recurrence rates at final follow-up (Group I: n = 2 vs Group II: n = 1; P = 0.363) were similar between the groups. CONCLUSION VATS thymectomy for thymoma is feasible, safe and has comparable mid-term oncological outcomes to trans-sternal thymectomy. Future research is required to evaluate long-term oncological outcomes of VATS thymectomy for thymoma in national registries and randomized, controlled trials.

Assessment of body image in patients undergoing surgery for colorectal cancer

PurposeThis study tested the scale properties and validity of the ten-item body image scale (BIS) in patients undergoing surgery for colorectal cancer (CRC).MethodsPatients completed the BIS and a validated measure of health-related quality of life (European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30) after open or laparoscopic resection. A sample of the patients had also previously completed questionnaires before and after surgery. Multi-trait scaling and factor analysis were used to examine the questionnaire scaling, and tests of reliability, clinical and construct validity were performed.ResultsEighty-two patients (48 male, 59 open, 23 laparoscopic) participated. Scaling analyses suggested a nine-item scale and one single item. This revised scale structure demonstrated good test-retest reliability (r = 0.94) and no overlap with the key domains of the EORTC QLQ-C30 (r < 0.40). Patients with a stoma reported significantly poorer BIS scores than those undergoing simple resection (p = 0.005).ConclusionsThis study provides psychometric and clinical evidence for a revised scale structure for the BIS in CRC, and the questionnaire is suitable to assess body image in CRC clinical trials.

Systematic review: quality of life after treatment for upper gastrointestinal cancer.

Purpose of reviewThe aim of this systematic review is to scrutinize and summarize the design, conduct and reporting standards of articles recently published describing health-related quality of life (HRQL) outcomes of treatment of upper gastrointestinal cancer. Recent findingsSome 2312 abstracts were published between January and July 2009 and initial elimination of papers reduced this number to 22 articles. Of these, 17 were judged to have robust HRQL methodology, but a further seven were excluded due to a high risk of bias in the study design. Ten articles (four randomized trials) were finally included in the review. Studies in curative treatments for oesophagogastric cancer show that surgery and chemoradiation therapy has a major short-term detrimental effect on HRQL, but recovery occurs within 6 months in long-term survivors but those not achieving a survival benefit report very poor HRQL. In advanced oesophageal cancer, 18 mm self-expandable metal stents and nonstent therapies lead to better short-term HRQL scores than nonexpandable stents and are the recommended standard of care. A small survival advantage and improved HRQL is conferred by adjuvant and palliative gemcitabine chemotherapy in patients with pancreatic cancer. SummaryThis review identified few well-designed studies that also included a robust assessment of HRQL. High-quality trials with reliable HRQL methods are required for outcomes to inform health policy and clinical decision-making.

Influence of higher valve gradient on long-term outcome after aortic valve repair.

BACKGROUND To evaluate the effect of higher post-operative valve gradient on freedom from valve re-intervention and death in patients undergoing aortic valve repair (AVr). METHODS Patients who underwent AVr between March 1996 and June 2010 were divided into 2 groups: I: peak gradient (PG) <20 mmHg (n=358) and II: PG ≥20 mmHg (n=113). Age (53.6±16.0 vs. 50.6±16.4 years; P=0.08), impaired LV (n=44, 12.2% vs. n=12, 10.6%: P=0.73) as well as the body surface area (1.97 vs. 1.95 m(2); P=0.4) were similar. Pre-operative AI >2+ was greater in Group II compared to Group I (n=78, 69.0% vs. n=192, 53.6%; P=0.004). Patients in Group II had higher proportion of bicuspid valves (BV) (n=58, 51.3% vs. n=106, 29.6%; P=0.0001) and restrictive valves (n=34, 30.0% vs. n=52, 14.5%; P=0.0001) while Marfan patients were seen only in Group I (n=19; P=0.010). Mean follow-up for Group I and Group II was 123.1±89.7 and 147.1±108.0 months, respectively. RESULTS In-hospital mortality was n=2 (0.5%) for Group I and none for Group II (P=1.0). Valve-sparing was higher in Group I (P=0.0001) but sub-commissural annuloplasty was similar (P=0.15). Shaving and/or decalcification was performed more in Group II (n=68, 60.1% vs. n=117, 32.6%; P=0.0001). Logistic regression analysis identified calcified, restrictive and bicuspid valves as independent predictors of PG ≥20 mmHg (P=0.04 for each). Predictors of re-operation were increased end-diastolic diameter (P=0.03) and younger age (P=0.007), but not PG ≥20 mmHg (P=0.98) (based on logistic regression). Overall 10-year cardiac survival and freedom from AV re-intervention was 82.3±4.6% vs. 89.5±4.2% (P=0.53) and 89.1±3.0% vs. 76.8±8.4% (P=0.02), in Group I and II, respectively (based on Kaplan-Meier analysis). Sub-group analysis showed that Group II patients requiring re-intervention (n=10) were younger (41.8±13.1 vs. 51.0±16.0 years; P=0.08) with similar proportion of bicuspid valves (n=6; 60%; P=0.74). The main reason for AV re-operation was aortic insufficiency (n=7) and AI + stenosis (n=3). CONCLUSIONS Higher gradient after AVr is associated with a reduced freedom from AV re-intervention, especially in younger patients.