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ObjectivesThe aim of this study is to explore the transparency of reporting primary outcome data within randomized controlled trials in the presence of missing data.Study design and settingA cohort examination of randomized controlled trials published in the four major medical journals (NEJM, JAMA, BMJ, Lancet) in 2013 and the first quarter of 2018. Data were extracted on reporting quality, the number of randomized participants, and the number of participants included within the primary outcome analysis with observed or imputed data.ResultsNinety-one of 159 (57%) studies analyzed from 2013 and 19 of 46 (41%) from 2018 included imputed data within the primary outcome analysis. Of these, only 13 of 91 (14%) studies from 2013 and 1 of 19 (5%) studies from 2018 explicitly reported the number of imputed values in the CONSORT diagram. Results' tables included levels of imputed data in 12 of 91 (13%) studies in 2013 and 4 of 19 (21%) in 2018. Consequently, identification of imputed data was a time-consuming task requiring extensive cross-referencing of all manuscript elements.ConclusionImputed primary outcome data are poorly reported. Participant flow diagrams frequently reported participant status which does not necessarily correlate to availability of data. We recommended that the number of imputed values are explicitly reported within CONSORT flow diagrams to increase transparency.

OBJECTIVE: The Core Outcome Set-STAndards for Development (COS-STAD) contains 11 standards (12 criteria) that are deemed to be the minimum design recommendations for all core outcome set (COS) development projects. Cancer is currently the disease area with the highest number of published COSs and is a major cause of worldwide morbidity and mortality. The aim of this study was to provide a baseline of cancer COS standards.STUDY DESIGN AND SETTING: Systematic reviews of COSs have identified 307 published COS studies. Cancer COSs were eligible for inclusion. Two reviewers independently assessed each of the COSs against the 12 criteria.RESULTS: Forty-nine cancer COSs were included; none met all 12 criteria representing the 11 minimum standards assessed in this study (range = 4-11 criteria, median = 6 criteria). All studies met the four scope standards, eight (16%) met all three standards for stakeholders involved, and two (4%) met all four standards for consensus process standards.CONCLUSION: With the exception of "scope" specification, there is much need for improvement. Poor reporting often made it challenging to assess whether minimum standards were met. The consensus process criteria were most difficult to assess, particularly those that required an assessment of being a priori. This is the first application of COS-STAD criteria to studies that have developed COSs and provides a baseline of cancer COS standards of development.

Objective To establish current practice of the management of learning and clustering effects, by treating center and surgeon, in the design and analysis of randomized surgical trials. Study design and setting The need for more surgical randomized trials is well recognized, and in recent years conduct has grown. Rigorous design, conduct, and analyses of such studies is important. Two methodological challenges are clustering effects, by center or surgeon, and surgical learning on trial outcomes. Sixteen leading journals were searched for randomized trials published within a two-year period. Data were extracted on considerations for learning and clustering effects. Results A total of 247 eligible studies were identified. Trials accounted for learning with 2% using an expertise-based design and 39% accounting for expertise by predefining surgeon credentials. One study analyzed learning. Clustering, by site and surgeon, was commonly managed by stratifying randomization, although one-third of center and 40% of surgeon stratified trials did not also adjust analysis. Conclusion Considerations for surgical learning and clustering effects are often unclear. Methods are varied and demonstrate poor adherence to established reporting guidelines. It is recommended that researchers consider these issues on a trial-by-trial basis, and report methods or justify where not needed to inform interpretation of results.

Introduction The introduction of biological and synthetic meshes has revolutionised the practice of implant-based breast reconstruction (IBBR) but evidence for effectiveness is lacking. The iBRA (implant Breast Reconstruction evAluation) study is a national trainee-led project that aims to explore the practice and outcomes of IBBR to inform the design of a future trial. We report the results of the iBRA National Practice Questionnaire (NPQ) which aimed to comprehensively describe the provision and practice of IBBR across the UK. Methods A questionnaire investigating local practice and service provision of IBBR developed by the iBRA Steering Group was completed by trainee and consultant leads at breast and plastic surgical units across the UK. Summary data for each survey item were calculated and variation between centres and overall provision of care examined. Results 81 units within 79 NHS-hospitals completed the questionnaire. Units offered a range of reconstructive techniques, with IBBR accounting for 70% (IQR:50–80%) of participating units' immediate procedures. Units on average were staffed by 2.5 breast surgeons (IQR:2.0–3.0) and 2.0 plastic surgeons (IQR:1.0–3.0) performing 35 IBBR cases per year (IQR:20-50). Variation was demonstrated in the provision of novel different techniques for IBBR especially the use of biological (n = 62) and synthetic (n = 25) meshes and in patient selection for these procedures. Conclusions The iBRA-NPQ has demonstrated marked variation in the provision and practice of IBBR in the UK. The prospective audit phase of the iBRA study will determine the safety and effectiveness of different approaches to IBBR and allow evidence-based best practice to be explored., Highlights • Implant breast reconstruction (IBBR) and the range of techniques is poorly evidence based. • We aimed to explore the current practice of IBBR in the UK to inform the design of a future definitive study. • Significant variation was demonstrated in the availability of techniques and patient selection for IBBR. • There is a need for well-designed studies to establish best practice and improve outcomes for patients considering IBBR.

Background: Malnutrition is common in patients undergoing gastric cancer resection, leading to weight loss, although little is known about how this impacts on health related quality of life (HRQL) This study aimed to explore the association between HRQL and weight loss in patients 2 years after curative gastric cancer resection. Methods: Consecutive patients undergoing curative gastric cancer resection and surviving at least 2 years without disease recurrence were recruited. Patients completed the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) and the specific module for gastric cancer (STO22) before and 2 years postoperatively and associations between HRQL scores and patients with and without ≥ 10% body weight loss (BWL) were examined. Results: A total of 76 patients were included, of whom 51 (67%) had BWL ≥ 10%. At 2 years postoperatively, BWL ≥ 10% was associated with deterioration of all functional aspects of quality of life, with persistent pain (21.6%), diarrhoea (13.7%) and nausea/vomiting (13.7%). By contrast, none of the patients with BWL < 10% experienced severe nausea/vomiting, pain or diarrhoea. Conclusions: Disabling symptoms occurred more frequently in patients with ≥ 10% BWL than in those with < 10% BWL, with a relevant negative impact on HRQL. A cause-effect relationship between weight loss and postoperative outcome remains unsolved.

Objective Women considering reconstructive breast surgery (RBS) require adequate information to make informed treatment decisions. This study explored patients' and health professionals' (HPs) perceptions of the adequacy of information provided for decision-making in RBS. Methods Semi-structured interviews with a purposive sample of patients who had undergone RBS and HPs providing specialist care explored participants' experiences of information provision prior to RBS. Results Professionals reported providing standardised verbal, written and photographic information about the process and outcomes of surgery. Women, by contrast, reported varying levels of information provision. Some felt fully-informed but others perceived they had received insufficient information about available treatment options or possible outcomes of surgery to make an informed decision. Conclusions Women need adequate information to make informed decisions about RBS and current practice may not meet women's needs. Minimum agreed standards of information provision, especially about alternative types of reconstruction, are recommended to improve decision-making in RBS.

ObjectiveThe aim of the study was to investigate how doctors considered and experienced the concept of equipoise while recruiting patients to randomized controlled trials (RCTs).Study Design and SettingIn-depth interviews with 32 doctors in six publicly funded pragmatic RCTs explored their perceptions of equipoise as they undertook RCT recruitment. The RCTs varied in size, duration, type of complex intervention, and clinical specialties. Interview data were analyzed using qualitative content and thematic analytical methods derived from grounded theory and synthesized across six RCTs.ResultsAll six RCTs suffered from poor recruitment. Doctors wanted to gather robust evidence but experienced considerable discomfort and emotion in relation to their clinical instincts and concerns about patient eligibility and safety. Although they relied on a sense of community equipoise to justify participation, most acknowledged having “hunches” about particular treatments and patients, some of which undermined recruitment. Surgeons experienced these issues most intensely. Training and support promoted greater confidence in equipoise and improved engagement and recruitment.ConclusionRecruitment to RCTs is a fragile process and difficult for doctors intellectually and emotionally. Training and support can enable most doctors to become comfortable with key RCT concepts including equipoise, uncertainty, patient eligibility, and randomization, promoting a more resilient recruitment process in partnership with patients.

Aim: The aim for this study is to investigate the methodological quality and potential impact on clinical decision making of patient reported outcome (PRO) assessment in randomised controlled trials (RCTs) in the gynecological cancer sites. Methods: A systematic review identified RCTs published between January 2004 and June 2012. Relevant studies were evaluated using a pre-determined extraction form which included: 1) Trial demographics and clinical and PRO characteristics; 2) level of PRO reporting; 3) Bias, assessed using the Cochrane Risk of Bias tool. All studies were additionally analysed in relation to their relevance in supporting clinical decision making. Results: Fifty RCTs enrolling 24991 patients were identified. In eight RCTs (16%) a PRO was the primary endpoint. Twenty-one studies (42%) were carried out in a multi-national context. Where statistically significant PRO differences between treatments were found, it related in most cases to both symptoms and domains other than symptoms (n=17, 57%). The majority of studies (n=42, 84%) did not mention the mode of administration nor the methods of collecting PRO data. Statistical approaches for dealing with missing data were only explicitly mentioned in 9 RCTs (18%). Sixteen RCTs (32%) were considered to be of high-quality and thus able to inform clinical decision making. Higher-quality PRO studies were generally associated with RCTs that were at a low risk of bias. Conclusion: This study showed that RCTs with PROs were generally well designed and conducted. In a third the information was very informative to fully understand the pros and cons of PROs treatment decision-making.

Background The EORTC QLQ-STO22 (STO22) was developed in 2001 to measure quality of life (QOL) of gastric cancer (GC) patients and is a well validated instrument. However, there are some points worth considering. Firstly, the treatment strategies have dramatically changed since 2001. In contrast to 20 years ago, diverse combination regimens with cytotoxic drugs and molecular agents are administered for advanced GC and multidisciplinary approaches including neoadjuvant therapy and minimally invasive surgery are the mainstay of treatment. Thus, the original STO22 might not adequately assess QOL of GC patients currently treated. Secondly, specialists and patients from East Asia were not involved in the development of the STO22. Consequently, QOL issues of East Asian patients might not be reflected in the original ST022. The EORTC QOL group in collaboration with the EORTC Gastrointestinal Tract Cancer Group and the JCOG, aim to update the existing STO22. Methods Updating the STO22 consists of four steps. Pre-phase 1: literature review of studies using the ST022 in East Asia. Phase 1: Compiling an exhaustive list of relevant QOL issues captured from the literature review and interviews with patients and health care professionals. Phase 2: operationalising new issues into items to make a provisional module. Phase 3: Pilot testing the provisional updated ST022 alongside the EORTC QLQ-C30 with patients who meet the eligibility criteria from Europe and East Asia to obtain a response score for each item, together with a rating of relevance and importance. Results This study is in progress and a grant application to the EORTC QOL group is under review. An interim report from pre-phase 1 and phase 1 will be presented at the congress. Conclusions The current STO22 module might need updating to capture the QOL issues related to the new and diverse treatments and to include the East Asian perspective. The updated STO22 would be used more globally across Europe and Asia.

BACKGROUND: Definitive chemoradiotherapy (CRT) is an alternative to surgery for the curative treatment of oesophageal carcinoma. The SCOPE1 trial aimed to investigate the addition of cetuximab to cisplatin and fluoropyrimidine-based definitive CRT in patients with localised oesophageal squamous-cell cancer and adenocarcinomas to assess activity, safety, and feasibility of use. METHODS: In this multicentre, randomised, open-label, phase 2/3 trial, we recruited patients aged 18 years and older from UK radiotherapy centres who had non-metastatic, histologically confirmed carcinoma of the oesophagus (adenocarcinoma, squamous-cell, or undifferentiated; WHO status 0-1; stage I-III disease) and been selected to receive definitive CRT. Patients were randomly assigned (1:1) via a central computerised system using stratified minimisation (with an 80:20 random element) to receive CRT alone or CRT with cetuximab (400 mg/m(2) on day 1 followed by 250 mg/m(2) weekly), stratified by recruiting hospital, primary reason for not having surgery, tumour histology, and tumour stage. CRT consisted of cisplatin 60 mg/m(2) (day 1) and capecitabine 625 mg/m(2) twice daily (days 1-21) for four cycles; cycles three and four were given concurrently with 50 Gy in 25 fractions of radiotherapy. The primary endpoint was the proportion of patients who were treatment failure free at week 24 for the phase 2 trial and overall survival for the phase 3 trial, both measured from randomisation. We analysed data by intention to treat. This trial is an International Standard Randomised Controlled Trial, number 47718479. FINDINGS: 258 patients (129 assigned to each treatment group) from 36 UK centres were recruited between Feb 7, 2008, and Feb 22, 2012. Recruitment was stopped without continuation to phase 3 because the trial met criteria for futility, but we continued to follow-up recruited patients until all had reached at least 24-week follow-up (median follow-up of patients who survived was 16.8 months [IQR 11.2-24.5]). Fewer patients were treatment failure free at 24 weeks in the CRT plus cetuximab group (79 of 119 patients [66·4%, 90% CI 58·6-73·6]) than in the CRT only group (93 of 121 patients [76.9%, 69.7-83.0]). The CRT plus cetuximab group also had shorter median overall survival (22.1 months [95% CI 15.1-24.5] vs 25.4 months [20.5-37.9]; adjusted HR 1.53 [95% CI 1.03-2.27]; p=0.035). Patients who received CRT plus cetuximab had more non-haematological grade 3 or 4 toxicities (102 [79%] of 129 patients vs 81 [63%] of 129 patients; p=0.004). The most common grade 3 or 4 toxicities were low white blood cell count (14 [11%] in the CRT plus cetuximab group vs 21 [16%] in the CRT only group), low absolute neutrophil count (15 [12%] vs 24 [19%]), fatigue (26 [20%] vs 25 [19%]), and dysphagia (35 [27%] vs 37 [29%]). INTERPRETATION: The addition of cetuximab to standard chemotherapy and radiotherapy cannot be recommended for patients with oesophageal cancer suitable for definitive CRT. FUNDING: Cancer Research UK.

With the recent trend of improved survival, there has been a marked interest in reviewing and refining the contribution of health related quality of life (HRQoL) outcome measures of treatment in advanced colorectal cancer. However, if HRQoL data are going to be of clinical value and help both physicians and patients make decisions there is a need for a consensus on both the design and methods of measurement of HRQoL in clinical trials, and an acknowledgement of the interpretation of the outcomes in clinical practice. Whilst it is encouraging to find that the quality of HRQoL measurement in clinical research has improved significantly over the last fifteen years, with a growing number of trial-based HRQoL studies, there is still the potential to improve the use of HRQoL in clinical decision making in advanced colorectal cancer. There is also the need to further refine measurement of HRQoL to provide useful data specific to these patients. It is anticipated that developments such as the liver metastases module EORTC (QLQ-LMC21) questionnaire will increase the sensitivity to change of the generic cancer measure, the EORTC QLQ-C30 and will provide essential HRQoL information regarding the use of treatments in both the curative and palliative settings. Furthermore, easy to use simple tools such as the "minimum standard checklist for evaluating HRQoL outcomes in cancer clinical trials" might be of help in guiding investigators on the basis of minimum criteria.

Background: The European Organisation for Research and Treatment of Cancer quality of life (EORTC QL) questionnaires are used in international trials and therefore standardised translation procedures are required. This report summarises the EORTC translation procedure, recent accomplishments and challenges. Methods: Translations follow a forward-backward procedure, independently carried out by two native-speakers of the target language. Discrepancies are arbitrated by a third consultant, and solutions are reached by consensus. Translated questionnaires undergo a pilot-testing. Suggestions are incorporated into the final questionnaire. Requests for translations originate from the module developers, physicians or pharmaceutical industry, and most translations are performed by professional translators. The translation procedure is managed and supervised by a Translation Coordinator within the EORTC QL Unit in Brussels. Results: To date, the EORTC QLQ-C30 has been translated and validated into more than 60 languages, with further translations in progress. Translations include all major Western, and many African and Asian languages. The following translation problems were encountered: lack of expressions for specific symptoms in various languages, the use of old-fashioned language, recent spelling reforms in several European countries and different priorities of social issues between Western and Eastern cultures. The EORTC measurement system is now registered for use in over 9000 clinical trials worldwide. Conclusions: The EORTC provides strong infrastructure and quality control to produce robust translated questionnaires. Nevertheless, translation problems have been identified. The key to improvements may lie in the particular features and strengths of the group, consisting of researchers from 21 countries representing 25 languages and include the development of simple source versions, the use of advanced computerised tools, rigorous pilot-testing, certification procedures and insights from a unique cross-cultural database of nearly 40,000 questionnaire responses.

The aim of this study was to identify factors associated significantly with hospitalised cancer patients' satisfaction with care. Patients were recruited from four geographical/cultural groups, including five European countries and Taiwan. They rated their level of satisfaction by completing the EORTC IN-PATSAT32 questionnaire at home. Additionally, data were collected on the sociodemographic and clinical characteristics and the quality of life of the patients, as well as on institutional characteristics. Of 762 patients recruited, 647 (85%) returned a completed questionnaire. The number of nurses and doctors per bed, institution size, geo-cultural origin, ward setting, teaching/non-teaching setting, treatment toxicity, global health status, participation in clinical trials and education level were all associated significantly at the multivariate level with satisfaction with doctor and nurse interpersonal skills, information provision, availability, and/or overall satisfaction. A number of patient-, institutional- and culture-related factors are associated with the perceived quality of cancer care. Future studies, with appropriate sampling frames and stratification procedures, are needed to better understand cross-national and cross-cultural differences in cancer patient satisfaction.

Management decisions for patients with cancer are frequently taken within the context of a multi-disciplinary team (MDT). There is little known, however, about decision-making at team meetings and whether MDT decisions are all implemented. This study evaluated team decision-making in upper gastrointestinal cancer. Consecutive MDT treatment decisions were recorded for patients with oesophageal, gastric, pancreatic and peri-ampullary tumours. Implementation of MDT decisions was investigated by examining hospital records. Where decisions were implemented it was recorded as concordant and discordant if the decision changed. Reasons for changes in MDT decisions were identified. 273 decisions were studied and 41 (15.1%) were discordant (not implemented), (95% confidence interval 11.1-20.0%). Looking at the reasons for discordance, 18 (43.9%) were due to co-morbid health issues, 14 (34.2%) related to patient choice and 8 (19.5%) decisions changed when more clinical information was available. For one discordant decision, the reason was not apparent. Discordant decisions were more frequent for patients with pancreatic or gastric carcinoma as compared to oesophageal cancer (P = 0.001). Results show that monitoring concordance between MDT decisions and final treatment implementation is useful to inform team decision-making. For upper gastrointestinal cancer, MDTs require more information about co morbid disease and patient choice to truly optimize the implementation of multi-disciplinary expertise.

Background A core outcome set (COS) is a standardised set of outcomes which should be measured and reported, as a minimum, in all effectiveness trials for a specific health area. This will allow results of studies to be compared, contrasted and combined as appropriate, as well as ensuring that all trials contribute usable information. The COMET (Core Outcome Measures for Effectiveness Trials) Initiative aims to support the development, reporting and adoption of COS. Central to this is a publically accessible online resource, populated with all available COS. The aim of the review we report here was to identify studies that sought to determine which outcomes or domains to measure in all clinical trials in a specific condition and to describe the methodological techniques used in these studies. Methods We developed a multi-faceted search strategy for electronic databases (MEDLINE, SCOPUS, and Cochrane Methodology Register). We included studies that sought to determine which outcomes/domains to measure in all clinical trials in a specific condition. Results A total of 250 reports relating to 198 studies were judged eligible for inclusion in the review. Studies covered various areas of health, most commonly cancer, rheumatology, neurology, heart and circulation, and dentistry and oral health. A variety of methods have been used to develop COS, including semi-structured discussion, unstructured group discussion, the Delphi Technique, Consensus Development Conference, surveys and Nominal Group Technique. The most common groups involved were clinical experts and non-clinical research experts. Thirty-one (16%) studies reported that the public had been involved in the process. The geographic locations of participants were predominantly North America (n = 164; 83%) and Europe (n = 150; 76%). Conclusions This systematic review identified many health areas where a COS has been developed, but also highlights important gaps. It is a further step towards a comprehensive, up-to-date database of COS. In addition, it shows the need for methodological guidance, including how to engage key stakeholder groups, particularly members of the public.

Little is known about patients' satisfaction with care in oncology hospitals across cultural contexts. Within the EORTC, we developed a 32-item satisfaction with care questionnaire to measure patients' appraisal of hospital doctors and nurses, as well as aspects of care organisation and services. This study assessed the psychometric characteristics of the questionnaire, the EORTC IN-PATSAT32, in a large, international sample of patients with cancer. Patients discharged from a surgery or medical oncology ward in nine countries were invited to complete at home the EORTC IN-PATSAT32 as well as other instruments for psychometric testing. Of 762 eligible patients recruited, 15% failed to return the questionnaire. Of the 647 compliant patients, 63% completed the questionnaires within 15 min and 82% required no help in its completion. Multitrait scaling analysis revealed excellent internal consistency and convergent validity, although some scales within the IN-PATSAT32 were relatively highly correlated. Test-retest data on 113 patients showed high reliability for most scales. Scales of the IN-PATSAT32 and of the QLQ-C30 were not significantly correlated, suggesting that the two questionnaires are assessing quite distinct concepts. The scales of the IN-PATSAT32 were able to discriminate clearly between patients with differing care expectations and differing intentions to recommend their hospital to others. This study supports the acceptability to patients, and the psychometric robustness of the EORTC IN-PATSAT32 questionnaire. Further studies are needed to assess the responsiveness of the questionnaire to changes in the structure and process of care over time.

Over the last decade, health related quality of life (HRQOL) investigations have become an increasingly important part of many cancer clinical trial research programs. This paper presents a review of all HRQOL studies published by the European Organisation for Research and Treatment of Cancer (EORTC), one of the largest clinical trials organisations in Europe. The findings highlight 24 clinical trials that have been published to date, enrolling over 9000 patients. HRQOL is fully integrated into EORTC phase III trials. In many trials, HRQOL provides a valuable source of additional information useful to both clinician and patient when making treatment decisions. Furthermore, several trials have found that the combined use of clinical information along with HRQOL data has led to the development of new standards of care in several different cancer sites. With more than 40 ongoing HRQOL studies in the EORTC, we expect HRQOL to play an even greater role over the coming decade in helping establish the optimal treatment and care approach for cancer patients.

The purpose of this study was to define the measurement properties and clinical validity of the European Organisation for Research and Treatment of Cancer (EORTC) questionnaire module to assess health-related quality of life (HRQL) in gastric cancer. The EORTC gastric cancer module, QLQ-STO 22, was administered with the QLQ-C30, core questionnaire, to 219 patients undergoing treatment with curative or palliative intent before and after treatment. Reliability and validity of the module was tested and patients' debriefing comments analysed. Compliance rates were high, questionnaires well accepted and less than 4% of items had missing data. Multi-trait scaling analyses and face validity refined the module to five scales and four single items. Scales distinguished between clinically distinct groups of patients and demonstrated treatment-induced changes over time. Test-retest scores demonstrated good reliability. The EORTC QLQ-STO 22 demonstrates psychometric and clinical validity that supports its use to supplement the EORTC QLQ-C30 to assess quality of life in patients with gastric cancer undergoing surgery, surgery and chemoradiotherapy, palliative chemotherapy, palliative surgery and best supportive care.

Quality of life (QL) is an important outcome measure within clinical trials. This paper describes the development of a QL module for patients with liver metastases from colorectal cancer (CRC) to supplement the European Organization for Research and Treatment of Cancer (EORTC) core QL questionnaire, the EORTC QLQ-C30. Phases 1–3 of the EORTC QL Group guidelines for developing QL modules were followed. The literature search generated 71 QL issues. Semi-structured interviews with eight healthcare professionals and 47 patients from the United Kingdom, France, Germany and Austria reduced the list to 23 issues. Questionnaire items were formulated to be compatible with the EORTC QLQ-C30. The provisional module was further tested in 102 patients resulting in a 21-item module, the QLQ-LMC21 (Liver Metastases Colorectal). A combination of the core questionnaire and the QLQ-LMC21 will provide essential QL information regarding the use of treatments in both the curative and palliative settings.

The redundancy and dysfunction of colonic interpositions is a recognized late complication of esophageal replacement, often occurring decades after the original surgery. A 34-year-old man, whose long-gap esophageal atresia was corrected as a child with large bowel interposition, presented with severe dysphagia and recurrent aspiration pneumonia. Imaging and endoscopy revealed a grossly abnormal and dysfunctional neo-esophagus. Symptoms were refractory to medical therapies, and necessitated occupational retirement on medical grounds. His case illustrates a successful surgical technique for correcting this complication.

One of the problems in assessing patients' quality of life (QL) is the availability of good robust measures that have demonstrated validity, reliability and sensitivity for changes over time, but also have been validated across a large group of culturally diverse nations. The European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Group (QLG) has recognised this and has established a substantial research programme with the aim of developing such tools, with particular relevance to cancer clinical trials. However, the management of a large set of items in multiple languages is difficult and very labour-intensive. Thus, to support the EORTC QLG research agenda, a computerised web-based database of all EORTC QLG measures and individual questionnaire items was developed. This database allows access to a pool of over 500 validated items in some 6000 translated versions. The database speeds up module development, ensures that questionnaires items have similar wording and provides rapid access to multiple translations.

Quality of life (QL) is an important outcome in clinical trials in oncology. There is currently no valid international QL measure for gastric cancer. This paper describes the development of a QL module for gastric cancer to supplement the European Organization for Research and Treatment of Cancer (EORTC) Quality of life (QLQ-C30) questionnaire. Phases I to III of module development were conducted in the United Kingdom, France, Germany and Spain according to EORTC QL Group guidelines. Twenty relevant QL issues were generated from the literature and interviews with health professionals (n=24) and patients (n=58). This produced a 24 item provisional module. Further testing in 115 patients resulted in the QLQ-STO22, containing 22 questions, conceptualised into five scales and four single items, related to disease symptoms, treatment side-effects and emotional issues specific to gastric cancer. The use of the QLQ-C30 supplemented by the QLQ-STO22 will provide a comprehensive QL measure for international trials in gastric cancer.

The European Organization for Research and Treatment of Cancer (EORTC) has taken a leading role in the development of the methodology of quality of life (QL) measurement. In the EORTC Quality of Life Study Group (QLSG) valid instruments to assess QL in a general manner and disease-specific modules have been developed to be used in oncological clinical trials. Statistical and methodological aspects of QL research are discussed. The application of QL assessments in clinical trials represents a subsequent challenge. To improve the practice of QL assessment in clinical trials an 'EORTC model' has been developed. This model requires the collaboration of liaison persons, the EORTC Cooperative Tumour Groups and the EORTC Data Centre Quality of Life Unit (QL Unit). Cooperation between these parties, protocol development and advantages and concerns of the model are mentioned in this paper. Finally, suggestions for improvement are proposed.

Quality of life (QOL) assessments in patients with oesophageal cancer should provide clinically meaningful data that can assist management decision making. This study describes the development of a specific module for oesophageal cancer to use with the European Organisation into Research and Treatment of Cancer (EORTC) QOL questionnaire, the EORTC QLQ-C30. Relevant QOL issues were generated from a literature search and interviews with patients and oesophageal cancer specialists. Issues were formulated into items compatible with those of the EORTC QLQ-C30. The provisional module was pretested in patients from the United Kingdom, Spain and Sweden. The resulting module, the QLQ-OES 24, includes 24 items conceptualised as containing six scales and five single items. The addition of an oesophageal cancer-specific module to the core questionnaire should improve the sensitivity and specificity of the core instrument to allow detection of even small benefits accrued from new treatment modalities.

There is an urgent need for rigorous scientific evaluation of emergent focal therapies of localised prostate cancer. New studies require consistency in design and delivery to produce reliable treatment effects and inform practice. Effective collaboration between stakeholders is also required to conduct high-quality studies and answer important questions. Early work has lacked uniform approaches. Eligibility criteria have been wide ranging. For example, prognostic variables have differed between studies thus invalidating findings; treatment protocols were often incompletely described or delivered, making replication of novel interventions in practice difficult; and a variety of outcomes were measured and reported at discrepant time points by different means, making results impossible to compare or combine and risking selective outcome reporting and bias. The evidence base from current studies, therefore, is poor, and data from the trials cannot be used efficiently in systematic reviews and meta-analyses. The time is right for investment in well-designed studies that yield optimal data, and the key to this is uniform study design and delivery, and real collaboration. The article by van den Bos et al. in this month’s issue of European Urology includes recommendations for a standardised design of trials of focal therapy [1]. This is an important step towards establishing research standards to inform future trials and the evidence base. The standards were identified using a three-stage scientific process for obtaining consensus from experts in the field. First, a list of key design features for a trial in focal therapy for prostate cancer was constructed from literature searches and used to create a questionnaire. The questionnaire had 36 items asking for a

surgery occurred in 3(5.6%) and 4(7.4%) patients in the CT group versus 4(7.8%) and 3(5.9%) patients in the CRT group. Conclusions: Part 1 of the TOPGEAR trial demonstrates preoperative CRT to be safe and feasible. With IDSMC recommendation the trial has proceeded to Part 2 where overall survival will be the primary end point. Current accrual is 170 patients recruited from 55 active sites. No conflict of interest.

Background Breast cancer affects one in eight women and approximately 40% will require a mastectomy. The loss of a breast can dramatically impact upon quality of life. Breast reconstruction is offered to improve outcomes. Making decisions about reconstructive surgery, however, is challenging, and women and health-care professionals need to assess the likely benefits of surgery against the risks of adverse outcomes. Decisions are informed by published outcomes and surgeon and patient preferences. Well-designed studies, such as multicentre, randomised, controlled trials (RCTs) provide the best evidence, but few RCTs have been undertaken in breast reconstruction. The aim of this study was therefore to explore the need for and the feasibility of RCTs in breast reconstruction. Methods Three systematic literature reviews (SRs) were done to critically appraised and summarise the quality of outcome reporting in breast reconstruction. Semistructured qualitative interviews were conducted with women and health-care professionals to explore decision making and attitudes to RCTs in breast reconstruction. The clinical outcomes SR included 123 observational studies and 11 RCTs. The majority were at high-risk of bias, and outcome reporting was heterogeneous. The cosmetic outcome SR included 122 studies. Cosmetic results were assessed by patients and health-care professionals, but the methodology was inconsistent. The patient-reported outcome SR included 62 studies, only 60% of which were considered methodologically robust. Findings 62 interviews with women and health-care professionals showed that decision making in breast reconstruction was complex. A third of women reported decisional regret, and insufficient time and information were identified as barriers to decision making. Inequalities in access to care, however, emerged as the most significant determinant of women's reconstructive experience. Both women and health-care professionals accepted RCTs in breast reconstruction in particular circumstances. Interpretation There is an urgent need for well-designed studies with standardised outcome assessment in breast reconstruction. Selected randomised trials may be feasible, but they are unlikely to address the key questions. Service reorganisation and interventions to improve decision making are needed to improve outcome for women considering breast reconstruction in the UK. Funding University of Bristol.