Refractory depression: mechanisms and evaluation of radically open dialectical behaviour therapy (RO-DBT) [REFRAMED]: protocol for randomised trial.

INTRODUCTION: Only 30-40% of depressed patients treated with medication achieve full remission. Studies that change medication or augment it by psychotherapy achieve only limited benefits, in part because current treatments are not designed for chronic and complex patients. Previous trials have excluded high-risk patients and those with comorbid personality disorder. Radically Open Dialectical Behaviour Therapy (RO-DBT) is a novel, transdiagnostic treatment for disorders of emotional over-control. The REFRAMED trial aims to evaluate the effectiveness and cost-effectiveness of RO-DBT for patients with treatment-resistant depression. METHODS AND ANALYSIS: REFRAMED is a multicentre randomised controlled trial, comparing 7 months of individual and group RO-DBT treatment with treatment as usual (TAU). Our primary outcome measure is depressive symptoms 12 months after randomisation. We shall estimate the cost-effectiveness of RO-DBT by cost per quality-adjusted life year. Causal analyses will explore the mechanisms by which RO-DBT is effective. ETHICS AND DISSEMINATION: The National Research Ethics Service (NRES) Committee South Central - Southampton A first granted ethical approval on 20 June 2011, reference number 11/SC/0146. TRIAL REGISTRATION NUMBER: ISRCTN85784627.

Bradykinin and cysteinyl leukotriene concentrations in cell-salvaged blood before and after passage through negatively charged filters during clinical use in cancer patients: a pilot study.

It has been suggested that giving cell-salvaged blood through a leucocyte depletion filter can cause hypotension due to bradykinin released when factor XII and platelets are activated by the negatively charged surface of the filter. We measured the concentration of bradykinin and cysteinyl leukotrienes in cell-salvaged blood sampled before and after passage through a negatively charged leucodepletion filter in 24 consecutive patients with gynaecological or bowel cancer undergoing elective surgery with cell salvage. In no case was an increase in bradykinin concentration observed after passage through the filter; in 23 patients the post-filtration bradykinin concentration was zero (p = 0.007). The change in the concentration of cysteinyl leukotrienes detected during passage across the filter was not statistically significant (p = 0.1). Our findings do not support the suggestion that either bradykinin or cysteinyl leukotrienes are generated in cell-salvaged blood during passage through leucodepletion filters.

Cancer of Oesophagus or Gastricus - New Assessment of Technology of Endosonography (COGNATE): report of pragmatic randomised trial.

BACKGROUND: Endoscopic ultrasonography is recommended for staging gastro-oesophageal cancers, but has never been evaluated. OBJECTIVE: COGNATE (Cancer of Oesophagus or Gastricus - New Assessment of Technology of Endosonography) therefore aimed to evaluate whether adding 'endoscopic ultrasound' (EUS) to the usual staging algorithm changes treatment, improves (quality-adjusted) survival, and uses resources cost-effectively. DESIGN: Pragmatic parallel-group trial. Patients with gastro-oesophageal cancer received standard staging algorithms. Multidisciplinary teams chose provisional management plans from endoscopic mucosal resection, immediate surgery, surgery after chemotherapy, or chemotherapy and radiotherapy. We used dynamic randomisation to allocate consenting patients remotely by telephone in equal proportions between EUS and not. Thereafter we recorded changes in management plan, use of health-care resources, and three aspects of participant-reported quality of life: generic [measured by European Quality of Life - 5 Dimensions (EQ-5D)], cancer related [Functional Assessment of Cancer Therapy - General scale (FACT-G)] and condition-specific [FACT - Additional Concerns scale (FACT-AC)]. We followed participants regularly until death or the end of the trial - for between 1 and 4.5 years. We devised a quality assurance programme to maintain standards of endosonographic reporting. SETTING: Eight British hospitals, of which two - one Scottish teaching hospital and one English district general hospital - contributed 80% of participants; we combined the other six for analysis. PARTICIPANTS: Patients were eligible if they had a diagnosis of gastro-oesophageal cancer, had not started treatment, were free of metastatic disease, were fit for surgery (even if not planned) and had American Society of Anesthesiologists and World Health Organization grades of less than 3. INTERVENTIONS: Intervention group: standard staging algorithm plus EUS; control group: standard staging algorithm. MAIN OUTCOME MEASURES: Primary: quality-adjusted survival. Secondary: survival; health-related quality of life (EQ-5D, FACT-G and FACT-AC scales); changes in management plan; and complete resection rate. Although blinding participants was neither possible nor desirable, those responsible for analysis remained blind until the Trial Steering Committee had reviewed the definitive analysis. RESULTS: We randomised 223 patients, of whom 213 yielded enough data for primary analysis. EUS improved survival adjusted for generic quality of life with a hazard ratio of 0.705 [95% confidence interval (CI) 0.499 to 0.995], and crude survival with a hazard ratio of 0.706 (95% CI 0.501 to 0.996). The benefits of EUS were significantly greater for those with poor initial quality of life, but did not differ between centres. EUS reduced net use of health-care resources by £2860 (95% 'bootstrapped' CI from -£2200 to £8000). Combining benefits and savings shows that EUS is likely to be cost-effective, with 96% probability of achieving the National Institute for Health and Care Excellence criterion of costing of < £20,000 to gain a QALY. There were no serious adverse reactions attributable to EUS. EUS enhanced the management plan for many participants, increased the proportion of tumours completely resected from 80% (44 out of 55) to 91% (48 out of 53), and improved the survival of those who changed plan; although underpinning the significant differences in outcome, none of these process differences was itself significant. CONCLUSION: Endoscopic ultrasound significantly improves (quality-adjusted) survival, has the potential to reduce health-care resource use (not statistically significant) and is probably cost-effective (with 96% probability). We recommend research into the best time to evaluate new technologies. TRIAL REGISTRATION: ISRCTN1444215. FUNDING: This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 17, No. 39. See the HTA programme website for further project information.

REMCARE: reminiscence groups for people with dementia and their family caregivers - effectiveness and cost-effectiveness pragmatic multicentre randomised trial.

OBJECTIVES: The aim of the REMiniscence groups for people with dementia and their family CAREgivers (REMCARE) study was to assess the effectiveness and cost-effectiveness of joint reminiscence groups for people with dementia and their family caregivers as compared with usual care. DESIGN: A multicentre, pragmatic randomised controlled trial with two parallel arms - an intervention group and a usual-care control group - was carried out. A restricted dynamic method of randomisation was used with an overall allocation ratio of 1 : 1, restricted to ensure intervention groups of a viable size. Assessments, blind to treatment allocation, were carried out at baseline, 3 months and 10 months (primary end point). SETTING: Most participants were recruited through NHS Memory Clinics and Community Mental Health Teams for older people. Assessments were usually carried out in the person's home, and treatment groups were held in a variety of community settings. PARTICIPANTS: A total of 488 individuals (mean age 77.5 years) with mild to moderate dementia (meeting Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition criteria), who were initially living in the community, and who had a relative or other caregiver maintaining regular contact, who could act as an informant and was willing and able to participate in the intervention, were recruited to the study. Most carers were spouses (71%). A total of 350 dyads completed the study. INTERVENTIONS: The intervention consisted of joint reminiscence groups held weekly for 12 consecutive weeks, followed by monthly maintenance sessions for a further 7 months. The sessions followed a treatment manual, and were led by two trained facilitators in each centre, supported by a number of volunteers. Up to 12 dyads were invited to attend each group. MAIN OUTCOME MEASURES: The primary outcome measures were self-reported quality of life for the person with dementia and psychological distress for the carer [General Health Questionnaire-28 item version (GHQ-28)]. Secondary outcome measures included autobiographical memory and activities of daily living for the person with dementia, carer stress for the carer and mood, relationship quality and service use and costs for both parties. RESULTS: The intention-to-treat analysis identified no differences in outcome between the intervention and control conditions on primary or secondary outcomes [self-reported quality of life in Alzheimer's disease: mean difference 0.07, standard error (SE) 0.65; F = 0.48; p = 0.53]. Carers of people with dementia allocated to the reminiscence intervention reported a significant increase in anxiety on a subscale of the GHQ-28 at the 10-month end point (mean difference 1.25, SE 0.5; F = 8.28; p = 0.04). Compliance analyses suggested some benefits for people with dementia who attended more reminiscence sessions; however, carers attending more groups showed increased caregiving stress. Use of health- and social-care services was modest, with no significant difference in service use between conditions. Owing to negligible difference in quality-adjusted life-year gains (derived from European Quality of Life-5 Dimensions) between the conditions the planned full economic analysis was curtailed. CONCLUSIONS: This trial does not provide support for the effectiveness or cost-effectiveness of joint reminiscence groups for people with dementia and their carers. Although there may be some beneficial effects for people with dementia who attend sessions as planned, this must be viewed in the context of raised anxiety and stress in their carers. The reasons for these discrepant outcomes need to be explored further, and may necessitate reappraisal of the movement towards joint interventions. TRIAL REGISTRATION: Current Controlled Trials ISRCTN42430123. FUNDING: This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 16, No. 48. See the HTA programme website for further project information.

Generalized method for adaptive randomization in clinical trials.

A flexible, generalized method of treatment allocation is proposed. The method uses a set of controlling parameters that enables the generic algorithm to produce a family of possible outcomes ranging from simple randomization to deterministic allocation. The method controls balance at stratum level, stratification level and overall without detriment to the predictability of the method. The paper lists the desirable characteristics of allocation methods and shows that the proposed method fulfils the majority and is easy to use in the clinical context, once the coding has been established. An explanation of the method for 2, 3 and 4 treatment group allocations is given. Simulations demonstrate the flexibility of the method.

Rural-urban differences in the effects on mental well-being of caring for people with stroke or dementia.

BACKGROUND: Rural and urban differences in the effects of care-giving are not well documented. This paper reports data on 122 carers for people with stroke or dementia living in rural and urban settings in Wales. METHOD: Carers completed a postal questionnaire, including the SF-12v2 Health Survey. Definitions of rural and urban were based on the Urban/Rural Indicator from the Office of National Statistics (ONS) All Fields Postcode Directory 2004. RESULTS: Carers' mean Mental Component Summary (MCS) score (adjusted for age and sex) was one standard deviation below the population mean (-12.03). Male carers living in urban areas reported better mental health than male carers in rural areas (p<0.05) and female carers in both settings (p<0.05). A full model and a parsimonious model were developed, using MCS scores as outcome variables. In the full model sitting service provision in rural and urban locations was linked to better carer mental health, while support from friends and family was linked to better mental health for urban carers only. CONCLUSION: Our findings indicate the existence of both gender and location differences in carer experiences.

Needle-stick injuries in primary care in Wales.

BACKGROUND: Accidental needle-stick injuries (NSIs) are a hazard for health-care workers and for the general public. OBJECTIVES: To estimate the presentation rate of NSIs to general medical practices, their relation to practice characteristics, and review practice policies for managing NSIs. METHOD: Descriptive study using logistic regression analysis. RESULTS: Annual rates of 2.73 (95% CI 2.08, 3.50) occupational NSIs per 100 clinical practice staff and 2.14 (95% CI 1.39, 3.13) non-occupational NSIs per 100,000 practice population were recorded. Stepwise logistic regressions showed that chance of a practice reporting at least one occupational NSI in previous five years was best predicted by being a single-handed practice (decreased odds). In contrast, the chance of a practice reporting at least one non-occupational NSI was best predicted by being a rural practice (increased odds). About one in five practices possessed no written policy on managing NSIs. Stepwise logistic regressions showed that the chance of a practice owning a NSI policy was best predicted by being located in an LHB area with a coastline (increased odds). CONCLUSION: NSIs are an important public health issue in Wales. We have tried to address the lack of guidance by developing new guidelines in Wales.

Adaptation of the Manchester-Minneapolis Quality of Life instrument for use in the UK population.

INTRODUCTION: The availability of health-related quality of life (HRQL) measures that are reliable, valid, brief and comprehensible and appropriate for use with UK children is limited. We report the validation of a HRQL measure suitable for UK use in healthy children, children with chronic disease conditions and socially disadvantaged children. PATIENTS: A total of 1238 children took part in the study, including healthy children as controls (n = 824) and five exemplar groups: children diagnosed with asthma (n = 87), diabetes (n = 103) or inflammatory bowel disease (IBD; n = 69), children in remission from cancer (n = 68) and children in public care (n = 87). METHODS: In phase I, the Manchester-Minneapolis Quality of Life instrument (MMQL) Child Form was translated into UK English. In phases II and III, the questionnaire was shortened and validated. RESULTS: MMQL was anglicised and shortened to five components comprising 29 items. Good internal reliability was found with alpha reaching at least 0.69 for all subscales. Construct validity was established through moderate correlations with comparable PedsQL subscales (Pearson's r ranged from 0.38 to 0.58, p<0.01). Discriminant validity was also demonstrated in children with asthma and IBD, children in remission from cancer and children in public care, all of whom reported significantly lower HRQL than healthy children. Children with diabetes showed similar HRQL to their healthy peers. Good reproducibility and moderate responsiveness were demonstrated for the new measure. CONCLUSIONS: The anglicised and shortened MMQL was shown to be valid and reliable and could be a valuable new tool for the assessment of HRQL in children.

Design of trials with dying patients: a feasibility study of cluster randomisation versus randomised consent.

There is little rigorous evidence to underpin clinical guidelines for palliative care. However, research in palliative care is difficult, especially with dying patients. Consent is a major issue, since staff do not wish to invite dying patients to participate in trials. We, therefore, conducted a feasibility study in two units within the North West Wales NHS Trust. We explored two novel approaches to research in palliative care -cluster randomisation and randomised consent. All patients admitted to the two units during the study were asked for permission to use their data for research. We allocated the two units, at random, to use cluster randomisation or randomised consent for three months, and then to crossover to the other design. Of 24 patients dying during cluster-randomised phases, 13 gave consent on admission to use their data and were, thus, eligible to enter the trial; however, defined eligibility criteria reduced these to six active participants. Of 29 patients dying during randomised consent phases, seven gave consent on admission to use their data; although two were eligible for randomisation, neither entered the trial. We judge that cluster randomisation is the more effective design for research with dying patients. Computer simulation, based on data from 1500 dying patients on the Welsh Integrated Care Pathway, shows that crossover cluster trials need much smaller samples than simple cluster trials. Furthermore, this study has shown that crossover cluster trials are entirely feasible. We recommend a 'definitive' trial to test the crossover design more widely.

Short report: encouraging GPs to complete postal questionnaires--one big prize or many small prizes? A randomized controlled trial.

BACKGROUND: Low response rates to surveys are a problem in general practice. There is evidence that offering GPs incentives improves response rates to postal questionnaires. However, there is less evidence about the most effective form of incentive. OBJECTIVE: Our trial aimed to maximize response to a postal questionnaire and to test the most effective form of incentive. METHODS: The study involved a randomized controlled trial of a postal survey RESULTS: The incentive of a lottery for six bottles of champagne generated a response rate of 79%. Furthermore, one chance of six bottles generated 9% more responses than six chances of one bottle. CONCLUSIONS: This study has established that, among incentives for postal questionnaires, one big prize improves the yield more than many small prizes despite the lower odds of winning. It has also confirmed that offering a modest incentive to GPs generates good response rates for postal questionnaires.

Clinical guidelines online: do they improve compliance?

BACKGROUND: The introduction of intranet services in a district general hospital provided an opportunity to put evidence based national guidelines online to facilitate access and promote application of best practice in acute medical care. This study evaluated the effectiveness of this approach. METHOD: Local guidelines were made available online at ward terminals after they had been distributed in paper form. An interrupted time series design was used to evaluate the impact on compliance with three preselected guidelines, which addressed the management of suspected deep vein thrombosis, upper gastrointestinal bleeding, and stroke. This was supplemented by a qualitative assessment of the views of medical staff. RESULTS: There was a significant increase in the adherence to the guidelines for stroke when they were made available online, but this was not demonstrable for deep vein thrombosis or upper gastrointestinal bleeding. Qualitative interviews with junior medical staff and consultants after the study was completed revealed that there was confusion regarding the application of the guidelines for deep vein thrombosis and little active support from the gastroenterologists for the guidelines for upper gastrointestinal bleeding. The stroke guidelines were actively promoted by their author and widely supported. CONCLUSION: Making guidelines available online will not be effective unless they are actively promoted and represent a consensus view.

Estimating the marginal value of 'better' research output: 'designed' versus 'routine' data in randomised controlled trials.

We recently completed a study which demonstrated that the costs of health technology assessment (HTA) by randomised controlled trial (RCT) can be reduced by substituting routine datasets for data designed and collected specifically for a trial. This cost reduction, however, had the effect of reducing the quality of the research output. In the present study we attempted to tease out the values attached to the 'better' information provided by designed data RCTs using a mock grants committee. Two valuation techniques, implied values and willingness to pay, were used. Ex ante valuations were determined by comparing alternative research proposals - a more costly version using designed data and a cheaper version using routine data. Ex post valuations were determined by comparing results of both versions. The exercise was performed on four exemplar studies. Overall, the committee expressed a general lack of trust towards routine data both ex ante and ex post and placed high values on the better information from the designed data studies - particularly information on preferences. This suggests that currently available routine datasets are not perceived to be able to provide efficient alternatives to designed data for RCTs.

Can randomised trials rely on existing electronic data? A feasibility study to explore the value of routine data in health technology assessment.

OBJECTIVES: To estimate the feasibility, utility and resource implications of electronically captured routine data for health technology assessment by randomised controlled trials (RCTs), and to recommend how routinely collected data could be made more effective for this purpose. DATA SOURCES: Four health technology assessments that involved patients under care at five district general hospitals in the UK using four conditions from distinct classical specialties: inflammatory bowel disease, obstructive sleep apnoea, female urinary incontinence, and total knee replacement. Patient-identifiable, electronically stored routine data were sought from the administration and clinical database to provide the routine data. REVIEW METHODS: Four RCTs were replicated using routine data in place of the data already collected for the specific purpose of the assessments. This was done by modelling the research process from conception to final writing up and substituting routine for designed data activities at appropriate points. This allowed a direct comparison to be made of the costs and outcomes of the two approaches to health technology assessment. The trial designs were a two-centre randomised trial of outpatient follow-up; a single-centre randomised trial of two investigation techniques; a three-centre randomised trial of two surgical operations; and a single-centre randomised trial of perioperative anaesthetic intervention. RESULTS: Generally two-thirds of the research questions posed by health technology assessment through RCTs could be answered using routinely collected data. Where these questions required analysis of NHS resource use, data could usually be identified. Clinical effectiveness could also be judged, using proxy measures for quality of life, provided clinical symptoms and signs were collected in sufficient detail. Patient and professional preferences could not be identified from routine data but could be collected routinely by adapting existing instruments. Routine data were found potentially to be cheaper to extract and analyse than designed data, and they also facilitate recruitment as well as have the potential to identify patient outcomes captured in remote systems that may be missed in designed data collection. The study confirmed previous evidence that the validity of routinely collected data is suspect, particularly in systems that are not under clinical and professional control. Potential difficulties were also found in identifying, accessing and extracting data, as well as in the lack of uniformity in data structures, coding systems and definitions. CONCLUSIONS: Routine data have the potential to support health technology assessment by RCTs. The cost of data collection and analysis is likely to fall, although further work is required to improve the validity of routine data, particularly in central returns. Better knowledge of the capability of local systems and access to the data held on them is also essential. Routinely captured clinical data have real potential to measure patient outcomes, particularly if the detail and precision of the data could be improved.

The development of a new site-specific measure of quality of life for breast problems: the Cardiff breast scales.

The management of women presenting to primary care with symptoms of breast disease is of increasing interest given recent organisational changes aimed at improving accuracy and speed of referrals. As part of a randomised controlled trial, 1063 women were recruited following a primary care consultation for a variety of breast-related problems. In the absence of a suitable outcome measure for such women, a site-specific instrument was developed to complement a generic quality of life scale (SF-36). Items were generated using key informant interviews with health professionals. Draft scale items were piloted using a postal questionnaire and subsequent patient debrief interviews. A sample of respondents were also sent the same questionnaire I month later to assess test-retest reliability. Across the whole sample (n = 848), three factors were identified: 'general well-being', 'concerns' and 'relationships'. These factors accounted for 60% of total variance. Evidence of scale validity, reliability and responsiveness are reported for this new outcome measure for use in women presenting with breast problems.

Shared care in gastroenterology: GPs' views of open access to out-patient follow-up for patients with inflammatory bowel disease.

OBJECTIVE: The aim of this study was to ascertain GPs' views about open access to out-patient follow-up for patients with inflammatory bowel disease (IBD). METHODS: Semi-structured interviews and a postal survey were carried out in general practices in West Glamorgan UK, each with at least one IBD patient taking part in a randomized trial of open access versus routine follow-up, which has been reported elsewhere. A total of 112 GPs from 53 general practices who referred the 180 study patients to specialist gastroenterological care in Neath or Swansea were included in the study. Main outcome measures were GPs' experience of the trial; preferences between methods of out-patient follow-up; and their views about enhancing open access follow-up. RESULTS: Sixty-nine GPs from 40 practices took part in the practice-specific data collection and 91 returned 156 patient-specific questionnaires. They expressed a strong preference for open access follow-up, for both specific patients (108/156 patients) and IBD patients in general (47/69 GPs). Preference for extending open access follow-up to other chronic conditions was not so strong (21/69 GPs). A substantial number of GPs considered their experience of the trial limited (30/69), and few GPs were aware of the shared care guideline distributed before the trial started (8/69). Few GPs encountered any problems in the management of the study patients (9/69) and <50% of the GPs used a Cumulative Encounter Form (29/69) developed for the study. Most GPs were supportive of giving patients written guidelines (56/69) and establishing a gastroenterological (GI) nurse practitioner (45/69). CONCLUSIONS: Open access follow-up of patients with IBD is supported by GPs. The approach would probably be improved by the distribution of written information to patients, the establishment of a GI nurse practitioner and an integrated approach between the nurse, hospital specialist, GP and patient.

Statistical assessment of the learning curves of health technologies.

OBJECTIVES: (1) To describe systematically studies that directly assessed the learning curve effect of health technologies. (2) Systematically to identify 'novel' statistical techniques applied to learning curve data in other fields, such as psychology and manufacturing. (3) To test these statistical techniques in data sets from studies of varying designs to assess health technologies in which learning curve effects are known to exist. METHODS - STUDY SELECTION (HEALTH TECHNOLOGY ASSESSMENT LITERATURE REVIEW): For a study to be included, it had to include a formal analysis of the learning curve of a health technology using a graphical, tabular or statistical technique. METHODS - STUDY SELECTION (NON-HEALTH TECHNOLOGY ASSESSMENT LITERATURE SEARCH): For a study to be included, it had to include a formal assessment of a learning curve using a statistical technique that had not been identified in the previous search. METHODS - DATA SOURCES: Six clinical and 16 non-clinical biomedical databases were searched. A limited amount of handsearching and scanning of reference lists was also undertaken. METHODS - DATA EXTRACTION (HEALTH TECHNOLOGY ASSESSMENT LITERATURE REVIEW): A number of study characteristics were abstracted from the papers such as study design, study size, number of operators and the statistical method used. METHODS - DATA EXTRACTION (NON-HEALTH TECHNOLOGY ASSESSMENT LITERATURE SEARCH): The new statistical techniques identified were categorised into four subgroups of increasing complexity: exploratory data analysis; simple series data analysis; complex data structure analysis, generic techniques. METHODS - TESTING OF STATISTICAL METHODS: Some of the statistical methods identified in the systematic searches for single (simple) operator series data and for multiple (complex) operator series data were illustrated and explored using three data sets. The first was a case series of 190 consecutive laparoscopic fundoplication procedures performed by a single surgeon; the second was a case series of consecutive laparoscopic cholecystectomy procedures performed by ten surgeons; the third was randomised trial data derived from the laparoscopic procedure arm of a multicentre trial of groin hernia repair, supplemented by data from non-randomised operations performed during the trial. RESULTS - HEALTH TECHNOLOGY ASSESSMENT LITERATURE REVIEW: Of 4571 abstracts identified, 272 (6%) were later included in the study after review of the full paper. Some 51% of studies assessed a surgical minimal access technique and 95% were case series. The statistical method used most often (60%) was splitting the data into consecutive parts (such as halves or thirds), with only 14% attempting a more formal statistical analysis. The reporting of the studies was poor, with 31% giving no details of data collection methods. RESULTS - NON-HEALTH TECHNOLOGY ASSESSMENT LITERATURE SEARCH: Of 9431 abstracts assessed, 115 (1%) were deemed appropriate for further investigation and, of these, 18 were included in the study. All of the methods for complex data sets were identified in the non-clinical literature. These were discriminant analysis, two-stage estimation of learning rates, generalised estimating equations, multilevel models, latent curve models, time series models and stochastic parameter models. In addition, eight new shapes of learning curves were identified. RESULTS - TESTING OF STATISTICAL METHODS: No one particular shape of learning curve performed significantly better than another. The performance of 'operation time' as a proxy for learning differed between the three procedures. Multilevel modelling using the laparoscopic cholecystectomy data demonstrated and measured surgeon-specific and confounding effects. The inclusion of non-randomised cases, despite the possible limitations of the method, enhanced the interpretation of learning effects. CONCLUSIONS - HEALTH TECHNOLOGY ASSESSMENT LITERATURE REVIEW: The statistical methods used for assessing learning effects in health technology assessment have been crude and the reporting of studies poor. CONCLUSIONS - NON-HEALTH TECHNOLOGY ASSESSMENT LITERATURE SEARCH: A number of statistical methods for assessing learning effects were identified that had not hitherto been used in health technology assessment. There was a hierarchy of methods for the identification and measurement of learning, and the more sophisticated methods for both have had little if any use in health technology assessment. This demonstrated the value of considering fields outside clinical research when addressing methodological issues in health technology assessment. CONCLUSIONS - TESTING OF STATISTICAL METHODS: It has been demonstrated that the portfolio of techniques identified can enhance investigations of learning curve effects. (ABSTRACT TRUNCATED)

The UK IBDQ-a British version of the inflammatory bowel disease questionnaire. development and validation.

Measurement of health-related quality of life (HRQL) is becoming more important in studies of patients with inflammatory bowel disease. The McMaster IBDQ is the most widely used HRQL instrument for these patients. However, its use with patients in the United Kingdom has not been validated. This study develops and validates a UK version of the McMaster IBDQ (UK IBDQ). The UK IBDQ was tested with two samples of patients for its reliability, validity, reproducibility, and responsiveness. The first sample consisted of 180 patients participating in a randomized clinical trial. The second was recruited from members of the National Association for Colitis and Crohns Disease. Reliability of the subscales and the summary score of the UK IBDQ is demonstrated by Cronbach's alpha and item-total correlations. Their validity is demonstrated by their correlations with SF-36 subscales and an empirical index of disease activity. Good intraclass correlations and responsiveness ratios show their reproducibility and responsiveness. The findings support the reliability, validity, reproducibility, and responsiveness of the UK IBDQ and its acceptability to patients in UK.

Open access follow up for inflammatory bowel disease: pragmatic randomised trial and cost effectiveness study.

OBJECTIVE: To evaluate whether follow up of patients with inflammatory bowel disease is better through open access than by routine booked appointments. DESIGN: Pragmatic randomised controlled trial. SETTING: Two district general hospitals in Swansea and Neath, Wales. PARTICIPANTS: 180 adults (78 with Crohn's disease, 77 ulcerative or indeterminate colitis, 25 ulcerative or idiopathic proctitis) recruited from outpatient clinics during October 1995 to November 1996. INTERVENTION: Open access follow up according to patient need. MAIN OUTCOME MEASURES: Generic (SF-36) and disease specific (UK inflammatory bowel disease questionnaire UKIBDQ) quality of life, number of primary and secondary care contacts, total resource use, and views of patients and general practitioners. RESULTS: There were no differences in generic or disease specific quality of life. Open access patients had fewer day visits (0.21 v 0. 42, P<0.05) and fewer outpatient visits ( 4.12 v 4.64, P<0.01), but some patients had difficulty obtaining an urgent appointment. There were no significant differences in specific investigations undertaken, inpatient days, general practitioner surgery or home visits, drugs prescribed, or total patient borne costs. Mean total cost in secondary care was lower for open access patients (P<0.05), but when primary care and patient borne costs were added there were no significant differences in total costs to the NHS or to society. General practitioners and patients preferred open access. CONCLUSIONS: Open access follow up delivers the same quality of care as routine outpatient care and is preferred by patients and general practitioners. It uses fewer resources in secondary care but total resource use is similar. Better methods of ensuring urgent access to outpatient clinics are needed.