Showing papers in "Health Technology Assessment in 2001"

Quality-of-life measures in chronic diseases of childhood

Abstract: Scope of the report This report is concerned with the evaluation of measures broadly designed to measure quality of life (QoL) in children and adolescents, either by self-report or proxy raters. Four research questions were identified: (1) To what extent are adult measures used in the evaluation of healthcare interventions in children? (2) How appropriate are adult measures for use with children? (3) To what extent do child self-reports correspond with assessments made by parents and carers? (4) How feasible and reliable are proxy measures of QoL in different disease contexts? Objectives (1) To review the state of the art with regard to measurement of QoL for children. (2) To make recommendations regarding the value of currently available measures for different purposes. (3) To identify further research needs. Method Electronic databases were searched for the period 1980-July 1999 for articles relating to measures of QoL, health status or well-being in children (under 18 years) with chronic disease. Handsearching of relevant journals and cross-referencing with reference lists in identified articles was also carried out. Key workers in the field were contacted for additional information, and the Internet was searched for relevant websites. Results Forty-three measures were identified (19 generic and 24 disease-specific). Sixteen measures allowed for completion by children and parent/caregiver; seven only allowed for completion by a proxy, and the remainder (n = 17) allowed only for child completion. The measures were described as QoL (n = 30), health status, (n = 2), perception of illness (n = 1), life satisfaction (n = 1) and quality of well-being (n = 1). RESULTS - TO WHAT EXTENT ARE ADULT MEASURES USED IN THE EVALUATION OF HEALTHCARE INTERVENTIONS IN CHILDREN?: Three studies were identified where adult measures were used with very few changes made for children. In 11 studies involving nine separate measures of QoL, adult measures were used as a model for work with children. RESULTS - HOW APPROPRIATE ARE ADULT MEASURES FOR USE WITH CHILDREN?: Adult measures may fail to tap the specific aspects of QoL that are important to the child. Measures based on adult work impose considerable response burden for children, in terms of length, reading skills and response scale. Wording and format of adult measures may need to be modified to account for children's cognitive and language skills. More basic research is needed to determine the level of response burden that children of different ages can manage. Assessments of difficulty (e.g. reading age) need to be routinely included with information about new measures. RESULTS - TO WHAT EXTENT DO CHILD SELF-REPORTS CORRESPOND WITH ASSESSMENTS MADE BY PARENTS AND CARERS?: Fourteen studies were identified in which concor-dance between child and parent was investigated, often as part of the development of a new measure. There was some evidence for greater concordance between child and parent for physical functioning compared with social and emotional domains, but greater heterogeneity in the latter measures may contribute to inconsistent results. There was no simple relationship between concordance and moderating variables such as age, gender and illness, but this conclusion was addressed only very rarely. RESULTS - HOW FEASIBLE AND RELIABLE ARE PROXY MEASURES OF QOL IN DIFFERENT DISEASE CONTEXTS?: Only five papers fulfilled the review criteria. Evaluation is difficult because authors fail to justify their choice of measures, and do not report critical information such as completion rates or missing data. Use of existing measures can potentially eliminate the time and expense required to develop a comprehensive measure of QoL, but a full battery of standardised tests may be expensive in terms of time for administration and scoring. In addition, battery measures tend to be lengthy and therefore demanding for sick patients. They are not recommended for work with children. RECOMMENDATIONS FOR RESEARCH - MINIMUM CRITERIA FOR NEW MEASURES: A set of procedures needs to be established for the development of new measures. These need to draw on the experience gained in development of child and adult measures to date. Basic research to enhance understanding of how children interpret questions in QoL measures is recommended. We need to understand the differences in meaning of items between children and adults, and between children of different ages. Some attempt to develop measures for children of 6 years or more have been reported, and these should be further developed. (ABSTRACT TRUNCATED)

Design and use of questionnaires: a review of best practice applicable to surveys of health service staff and patients

Abstract: Questionnaires are often used to collect primaryquantitative data from patients and healthcareprofessionals. The aim is to gather valid, reliable,unbiased and discriminatory data from a represen-tative sample of respondents. However, theinformation yielded is subject to error and biasfrom a range of sources. Close attention to issuesof questionnaire design and survey administrationcan reduce these errors.

Eliciting public preferences for healthcare: a systematic review of techniques.

Abstract: Background Limited resources coupled with unlimited demand for healthcare mean that decisions have to be made regarding the allocation of scarce resources across competing interventions. Policy documents have advocated the importance of public views as one such criterion. In principle, the elicitation of public values represents a big step forward. However, for the exercise to be worthwhile, useful information must be obtained that is scientifically defensible, whilst decision-makers must be able and willing to use it. Aims and objectives The aim was to identify techniques that could be reasonably used to elicit public views on the provision of healthcare. Hence, the objectives were: (1) to identify research methods with the potential to take account of public views on the delivery of healthcare; (2) to identify criteria for assessing these methods; (3) to assess the methods identified according to the predefined criteria; (4) to assess the importance of public views vis-a-vis other criteria for setting priorities, as judged by a sample of decision-makers; (5) to make recommendations regarding the use of methods and future research. Methods A systematic literature review was carried out to identify methods for eliciting public views. Criteria currently used to evaluate such methods were identified. The methods identified were then evaluated according to predefined criteria. A questionnaire-based survey assessed the relative importance of public views vis-a-vis five other criteria for setting priorities: potential health gain; evidence of clinical effectiveness; budgetary impact; equity of access and health status inequalities; and quality of service. Two techniques were used: choice-based conjoint analysis and allocation of points technique. The questionnaire was sent to 143 participants. A subsample was followed up with a telephone interview. Results The methods identified were classified as quantitative or qualitative. RESULTS - QUANTITATIVE TECHNIQUES: Quantitative techniques, classified as ranking, rating or choice-based approaches, were evaluated according to eight criteria: validity; reproducibility; internal consistency; acceptability to respondents; cost (financial and administrative); theoretical basis; whether the technique offered a constrained choice; and whether the technique provided a strength of preference measure. Regarding ranking exercises, simple ranking exercises have proved popular, but their results are of limited use. The qualitative discriminant process has not been used to date in healthcare, but may be useful. Conjoint analysis ranking exercises did well against the above criteria. A number of rating scales were identified. The visual analogue scale has proved popular within the quality-adjusted life-year paradigm, but lacks constrained choice and may not measure strength of preference. However, conjoint analysis rating scales performed well. Methods identified for eliciting attitudes include Likert scales, the semantic differential technique, and the Guttman scale. These methods provide useful information, but do not consider strength of preference or the importance of different components within a total score. Satisfaction surveys have been frequently used to elicit public opinion. Researchers should ensure that they construct sensitive techniques, despite their limited use, or else use generic techniques where validity has already been established. Service quality (SERVQUAL) appears to be a potentially useful technique and its application should be researched. Three choice-based techniques with a limited application in healthcare are measure of value, the analytical hierarchical process and the allocation of points technique, while those more widely used, and which did well against the predefined criteria, include standard gamble, time trade-off, discrete choice conjoint analysis and willingness to pay. Little methodological work is currently available on the person trade-off. RESULTS - QUALITATIVE TECHNIQUES: Qualitative techniques were classified as either individual or group-based approaches. Individual approaches included one-to-one interviews, dyadic interviews, case study analyses, the Delphi technique and complaints procedures. Group-based methods included focus groups, concept mapping, citizens' juries, consensus panels, public meetings and nominal group techniques. Six assessment criteria were identified: validity; reliability; generalisability; objectivity; acceptability to respondents; and cost. Whilst all the methods have distinct strengths and weaknesses, there is a lot of ambiguity in the literature. Whether to use individual or group methods depends on the specific topic being discussed and the people being asked, but for both it is crucial that the interviewer/moderator remains as objective as possible. The most popular and widely used such methods were one-to-one interviews and focus groups. (ABSTRACT TRUNCATED)

Subgroup analyses in randomised controlled trials: quantifying the risks of false-positives and false-negatives

Abstract: BACKGROUND Subgroup analyses are common in randomised controlled trials (RCTs). There are many easily accessible guidelines on the selection and analysis of subgroups but the key messages do not seem to be universally accepted and inappropriate analyses continue to appear in the literature. This has potentially serious implications because erroneous identification of differential subgroup effects may lead to inappropriate provision or withholding of treatment. OBJECTIVES (1) To quantify the extent to which subgroup analyses may be misleading. (2) To compare the relative merits and weaknesses of the two most common approaches to subgroup analysis: separate (subgroup-specific) analyses of treatment effect and formal statistical tests of interaction. (3) To establish what factors affect the performance of the two approaches. (4) To provide estimates of the increase in sample size required to detect differential subgroup effects. (5) To provide recommendations on the analysis and interpretation of subgroup analyses. METHODS The performances of subgroup-specific and formal interaction tests were assessed by simulating data with no differential subgroup effects and determining the extent to which the two approaches (incorrectly) identified such an effect, and simulating data with a differential subgroup effect and determining the extent to which the two approaches were able to (correctly) identify it. Initially, data were simulated to represent the 'simplest case' of two equal-sized treatment groups and two equal-sized subgroups. Data were first simulated with no differential subgroup effect and then with a range of types and magnitudes of subgroup effect with the sample size determined by the nominal power (50-95%) for the overall treatment effect. Additional simulations were conducted to explore the individual impact of the sample size, the magnitude of the overall treatment effect, the size and number of treatment groups and subgroups and, in the case of continuous data, the variability of the data. The simulated data covered the types of outcomes most commonly used in RCTs, namely continuous (Gaussian) variables, binary outcomes and survival times. All analyses were carried out using appropriate regression models, and subgroup effects were identified on the basis of statistical significance at the 5% level. RESULTS While there was some variation for smaller sample sizes, the results for the three types of outcome were very similar for simulations with a total sample size of greater than or equal to 200. With simulated simplest case data with no differential subgroup effects, the formal tests of interaction were significant in 5% of cases as expected, while subgroup-specific tests were less reliable and identified effects in 7-66% of cases depending on whether there was an overall treatment effect. The most common type of subgroup effect identified in this way was where the treatment effect was seen to be significant in one subgroup only. When a simulated differential subgroup effect was included, the results were dependent on the nominal power of the simulated data and the type and magnitude of the subgroup effect. However, the performance of the formal interaction test was generally superior to that of the subgroup-specific analyses, with more differential effects correctly identified. In addition, the subgroup-specific analyses often suggested the wrong type of differential effect. The ability of formal interaction tests to (correctly) identify subgroup effects improved as the size of the interaction increased relative to the overall treatment effect. When the size of the interaction was twice the overall effect or greater, the interaction tests had at least the same power as the overall treatment effect. However, power was considerably reduced for smaller interactions, which are much more likely in practice. The inflation factor required to increase the sample size to enable detection of the interaction with the same power as the overall effect varied with the size of the interaction. For an interaction of the same magnitude as the overall effect, the inflation factor was 4, and this increased dramatically to of greater than or equal to 100 for more subtle interactions of < 20% of the overall effect. Formal interaction tests were generally robust to alterations in the number and size of the treatment and subgroups and, for continuous data, the variance in the treatment groups, with the only exception being a change in the variance in one of the subgroups. In contrast, the performance of the subgroup-specific tests was affected by almost all of these factors with only a change in the number of treatment groups having no impact at all. CONCLUSIONS While it is generally recognised that subgroup analyses can produce spurious results, the extent of the problem is almost certainly under-estimated. This is particularly true when subgroup-specific analyses are used. In addition, the increase in sample size required to identify differential subgroup effects may be substantial and the commonly used 'rule of four' may not always be sufficient, especially when interactions are relatively subtle, as is often the case. CONCLUSIONS--RECOMMENDATIONS FOR SUBGROUP ANALYSES AND THEIR INTERPRETATION: (1) Subgroup analyses should, as far as possible, be restricted to those proposed before data collection. Any subgroups chosen after this time should be clearly identified. (2) Trials should ideally be powered with subgroup analyses in mind. However, for modest interactions, this may not be feasible. (3) Subgroup-specific analyses are particularly unreliable and are affected by many factors. Subgroup analyses should always be based on formal tests of interaction although even these should be interpreted with caution. (4) The results from any subgroup analyses should not be over-interpreted. Unless there is strong supporting evidence, they are best viewed as a hypothesis-generation exercise. In particular, one should be wary of evidence suggesting that treatment is effective in one subgroup only. (5) Any apparent lack of differential effect should be regarded with caution unless the study was specifically powered with interactions in mind. CONCLUSIONS--RECOMMENDATIONS FOR RESEARCH: (1) The implications of considering confidence intervals rather than p-values could be considered. (2) The same approach as in this study could be applied to contexts other than RCTs, such as observational studies and meta-analyses. (3) The scenarios used in this study could be examined more comprehensively using other statistical methods, incorporating clustering effects, considering other types of outcome variable and using other approaches, such as Bootstrapping or Bayesian methods.

Action research: a systematic review and guidance for assessment.

Abstract: Authors' objectives 1. To provide a definition of action research. 2. To identify action research projects conducted in UK healthcare settings. 3. To analyse the identified action research in relation to: project aims reasons for choosing action research issues addressed by action research outcomes and impacts strengths and limitations. 4. To develop guidance for the assessment of action research proposals and reports.

Comparison of the effectiveness of inhaler devices in asthma and chronic obstructive airways disease: a systematic review of the literature

Abstract: Background Asthma and chronic obstructive pulmonary disease (COPD) are common diseases of the airways and lungs that have a major impact on the health of the population. The mainstay of treatment is by inhalation of medication to the site of the disease process. This can be achieved by a number of different device types, which have wide variations in costs to the health service. A number of different inhalation devices are available. The pressurised metered-dose inhaler (pMDI) is the most commonly used and cheapest device, which may also be used in conjunction with a spacer device. Newer chlorofluorocarbons (CFC)-free inhaler devices using hydrofluoroalkanes (HFAs) have also been developed. The drug is dissolved or suspended in the propellant under pressure. When activated, a valve system releases a metered volume of drug and propellant. Other devices include breath-actuated pMDIs (BA-pMDI), such as Autohaler and Easi-Breathe. They incorporate a mechanism activated during inhalation that triggers the metered-dose inhaler. Dry powder inhalers (DPI), such as Turbohaler, Diskhaler, Accuhaler and Rotahaler, are activated by inspiration by the patient. The powdered drug is dispersed into particles by the inspiration. With nebulisers oxygen, compressed air, or ultrasonic power is used to break up solutions or suspensions of medication into droplets for inhalation. The aerosol is administered by mask or by a mouthpiece. There has been no previous systematic review of the evidence of clinical effectiveness and cost-effectiveness of these different inhaler devices. Objectives To review systematically the clinical effectiveness and cost-effectiveness of inhaler devices in asthma and COPD. Methods The different aspects of inhaler devices were separated into the most clinically relevant comparisons. Methods involved systematic searching of electronic databases and bibliographies for randomised controlled trials (RCTs) and systematic reviews. Pharmaceutical companies and experts in the field were contacted for further information. Trials that met the inclusion criteria were appraised and data extraction was under-taken by one reviewer and checked by a second reviewer, with any discrepancies being resolved through agreement. RESULTS--IN VITRO CHARACTERISTICS VERSUS IN VIVO TESTING AND CLINICAL RESPONSE: There is evidence that when comparative testing is performed on inhaler devices using the same methods, there is some correlation between particle size measurements and clinical response. However, the measurements are dependent upon the methods used, and a single measure of a device in isolation is of limited value. Also, there is little data on comparing devices of different types. There is currently insufficient data to verify the ability of in vitro assessments to predict inhaler performance in vivo. RESULTS--EFFECTIVENESS OF METERED-DOSE INHALERS FOR THE DELIVERY OF CORTICOSTEROIDS IN ASTHMA: The review of three trials in children and 21 trials in adults demonstrated no evidence to suggest clinical benefits of any other inhaler device over a pMDI in corticosteroid delivery. RESULTS--EFFECTIVENESS OF METERED-DOSE INHALERS FOR THE DELIVERY OF BETA-AGONISTS IN STABLE ASTHMA: In children, 11 studies were reviewed, of which seven compared the Turbohaler with the pMDI. One study found a significant treatment difference in peak expiratory flow rate, although there were differences in the patients' baseline characteristics. In adults, a review of 70 studies found no demonstrable difference in the clinical bronchodilator effect of short-acting b2-agonists delivered by the standard pMDI compared with that produced by any other DPI, HFA-pMDI or the Autohaler device. The finding that HFA-pMDIs may reduce treatment failure and oral steroid requirement in beta-agonist delivery needs further confirmatory research in adequately randomised clinical trials. RESULTS--EFFECTIVENESS OF NEBULISERS VERSUS METERED-DOSE INHALERS FOR THE DELIVERY OF BRONCHODILATORS IN STABLE ASTHMA: In children, three included trials compared different devices with a nebuliser and demonstrated no evidence of clinical superiority of nebulisers over inhaler devices in bronchodilator delivery. A total of 23 studies in adults found no equivalence for the main pulmonary outcomes and no evidence of difference in other outcomes. RESULTS--EFFECTIVENESS OF METERED-DOSE INHALERS FOR THE DELIVERY OF BETA-AGONISTS IN COPD: Only two studies were included in this review. No evidence of clinical difference was found in beta-agonist delivery. RESULTS--EFFECTIVENESS OF NEBULISERS VERSUS METERED-DOSE INHALERS FOR THE DELIVERY OF BRONCHODILATORS IN COPD: Evidence from 14 trials demonstrated equivalence for the main outcomes of pulmonary function. For other outcomes there was no evidence of treatment difference in bronchodilator delivery. RESULTS--PATIENTS' ABILITY TO USE METERED-DOSE INHALERS: Differences among studies and the heterogeneity of the results make it difficult to draw conclusions about inhaler technique differences between device types. The review of technique after teaching the correct technique suggests that there is no difference in patients' ability to use DPI or pMDIs. RESULTS--ECONOMIC ANALYSIS: The total number of NHS prescriptions for inhaler therapy for asthma in 1998 was over 31 million, with a net ingredient cost in excess of 392 million GB pounds. This economic assessment uses decision analysis to estimate the relative cost-effectiveness of inhaler devices for the delivery of bronchodilator and corticosteroid inhaled therapy. Overall, there were no differences in patient outcomes among the devices. On the assumption that the devices were clinically equivalent, pMDIs were the most cost-effective devices for asthma treatment. Conclusions This systematic review examined the evidence from clinical trials evaluating the clinical effectiveness of different inhaler devices in the delivery of inhaled corticosteroids and beta2-bronchodilators for patients with asthma and COPD. The evidence from the published clinical literature demonstrates no difference in clinical effectiveness between nebulisers and alternative inhaler devices compared to standard pMDI with or without a spacer device. The cost-effectiveness evidence therefore favours pMDIs (or the cheapest inhaler device) as first-line treatment in all patients with stable asthma unless other specific reasons are identified. Patients can use pMDIs as effectively as other inhaler devices as long as the correct inhalation technique is taught. CONCLUSIONS--RECOMMENDATIONS FOR RESEARCH: Further clinical trials are required to demonstrate any differences in the clinical effectiveness and cost-effectiveness of inhaler devices and nebulisers compared with pMDIs. These should be of sufficient statistical power and methodological rigour to demonstrate any clinical benefit. Trials should be undertaken in community settings to ensure the generalisability of results. Outcome measures should be more patient-centred and report adverse effects more completely. Reporting of data from trials should be improved.

The measurement and monitoring of surgical adverse events.

Abstract: Background Surgical adverse events contribute significantly to postoperative morbidity, yet the measurement and monitoring of events is often imprecise and of uncertain validity. Given the trend of decreasing length of hospital stay and the increase in use of innovative surgical techniques--particularly minimally invasive and endoscopic procedures--accurate measurement and monitoring of adverse events is crucial. Objectives The aim of this methodological review was to identify a selection of common and potentially avoidable surgical adverse events and to assess whether they could be reliably and validly measured, to review methods for monitoring their occurrence and to identify examples of effective monitoring systems for selected events. This review is a comprehensive attempt to examine the quality of the definition, measurement, reporting and monitoring of selected events that are known to cause significant postoperative morbidity and mortality. METHODS - SELECTION OF SURGICAL ADVERSE EVENTS: Four adverse events were selected on the basis of their frequency of occurrence and likelihood of evidence of measurement and monitoring: (1) surgical wound infection; (2) anastomotic leak; (3) deep vein thrombosis (DVT); (4) surgical mortality. Surgical wound infection and DVT are common events that cause significant postoperative morbidity. Anastomotic leak is a less common event, but risk of fatality is associated with delay in recognition, detection and investigation. Surgical mortality was selected because of the effort known to have been invested in developing systems for monitoring surgical death, both in the UK and internationally. Systems for monitoring surgical wound infection were also included in the review. METHODS - LITERATURE SEARCH: Thirty separate, systematic literature searches of core health and biomedical bibliographic databases (MEDLINE, EMBASE, CINAHL, HealthSTAR and the Cochrane Library) were conducted. The reference lists of retrieved articles were reviewed to locate additional articles. A matrix was developed whereby different literature and study designs were reviewed for each of the surgical adverse events. Each article eligible for inclusion was independently reviewed by two assessors. METHODS - CRITICAL APPRAISAL: Studies were appraised according to predetermined assessment criteria. Definitions and grading scales were assessed for: content, criterion and construct validity; repeatability; reproducibility; and practicality (surgical wound infection and anastomotic leak). Monitoring systems for surgical wound infection and surgical mortality were assessed on the following criteria: (1) coverage of the system; (2) whether or not denominator data were collected; (3) whether standard and agreed definitions were used; (4) inclusion of risk adjustment; (5) issues related to data collection; (6) postdischarge surveillance; (7) output in terms of feedback and wider dissemination. RESULTS - SURGICAL WOUND INFECTION: A total of 41 different definitions and 13 grading scales of surgical wound infection were identified from 82 studies. Definitions of surgical wound infection varied from presence of pus to complex definitions such as those proposed by the Centres for Disease Control in the USA. A small body of literature has been published on the content, criterion and construct validity of different definitions, and comparisons have been made against wound assessment scales and multidimensional indices. There are examples of comprehensive hospital-based monitoring systems of surgical wound infection, mainly under the auspices of nosocomial surveillance. To date, however, there is little evidence of systematic measurement and monitoring of surgical wound infection after hospital discharge. RESULTS - ANASTOMOTIC LEAK: Over 40 definitions of anastomotic leak were extracted from 107 studies of upper gastrointestinal, hepatopancreaticobiliary and lower gastrointestinal surgery. No formal evaluations were found that assessed the validity or reliability of definitions or severity scales of anastomotic leak. One definition was proposed during a national consensus workshop, but no evidence of its use was found in the surgical literature. The lack of a single definition or gold standard hampers comparison of postoperative anastomotic leak rates between studies and institutions. RESULTS - DEEP VEIN THROMBOSIS: Although a critical review of the DVT literature could not be completed within the realms of this review, it was evident that a number of new techniques for the detection and diagnosis of DVT have emerged in the last 20 years. The group recommends a separate review be undertaken of the different diagnostic tests to detect DVT. RESULTS - SURGICAL MORTALITY MONITORING SYSTEMS: The definition of surgical mortality is relatively consistent between monitoring systems, but duration of follow-up of death postdischarge varies considerably. The majority of systems report in-hospital mortality rates; only some have the potential to link deaths to national death registers. Risk assessment is an important factor and there should be a distinction between recording pre-intervention factors and postoperative complications. A variety of risk scoring systems was identified in the review. Factors associated with accurate and complete data collection include the employment of local, dedicated personnel, simple and structured prompts to ensure that clinical input is complete, and accurate and automated data capture and transfer. Conclusions The use of standardised, valid and reliable definitions is fundamental to the accurate measurement and monitoring of surgical adverse events. This review found inconsistency in the quality of reporting of postoperative adverse events, limiting accurate comparison of rates over time and between institutions. The duration of follow-up for individual events will vary according to their natural history and epidemiology. Although risk-adjusted aggregated rates can act as screening or warning systems for adverse events, attribution of whether events are avoidable or preventable will invariably require further investigation at the level of the individual, unit or department. CONCLUSIONS - RECOMMENDATIONS FOR RESEARCH: (1) A single, standard definition of surgical wound infection is needed so that comparisons over time and between departments and institutions are valid, accurate and useful. Surgeons and other healthcare professionals should consider adopting the 1992 Centers for Disease Control (CDC) definition for superficial incisional, deep incisional and organ/space surgical site infection for hospital monitoring programmes and surgical audits. There is a need for further methodological research into the performance of the CDC definition in the UK setting. (2) There is a need to formally assess the reliability of self-diagnosis of surgical wound infection by patients. (3) There is a need to assess formally the reliability of case ascertainment by infection control staff. (4) Work is needed to create and agree a standard, valid and reliable definition of anastomotic leak which is acceptable to surgeons. (5) A systematic review is needed of the different diagnostic tests for the diagnosis of DVT. (6) The following variables should be considered in any future DVT review: anatomical region (lower limb, upper limb, pelvis); patient presentation (symptomatic, asymptomatic); outcome of diagnostic test (successfully completed, inconclusive, technically inadequate, negative); length of follow-up; cost of test; whether or not serial screening was conducted; and recording of laboratory cut-off values for fibrinogen equivalent units. (7) A critical review is needed of the surgical risk scoring used in monitoring systems. (8) In the absence of automated linkage there is a need to explore the benefits and costs of monitoring in primary care. (9) The growing potential for automated linkage of data from different sources (including primary care, the private sector and death registers) needs to be explored as a means of improving the ascertainment of surgical complications, including death. This linkage needs to be within the terms of data protection, privacy and human rights legislation. (10) A review is needed of the extent of the use and efficiency of routine hospital data versus special collections or voluntary reporting.

Effects of educational and psychosocial interventions for adolescents with diabetes mellitus: a systematic review.

Abstract: BACKGROUND: Insulin-dependent diabetes mellitus, also known as type 1 diabetes, is a life-threatening condition and is the third most common chronic illness among young people. As a result of minimal or non-existent insulin production, people with diabetes must take over the normally automatic task of regulation of blood glucose levels. This is achieved by a complex regimen involving multiple, daily administrations of insulin coordinated with dietary intake and energy expenditure and monitored by blood glucose testing. OBJECTIVES: To examine the effectiveness of educational and psychosocial interventions for adolescents with type 1 diabetes designed to improve their diabetes management. Specifically, it addressed the following research questions: (1) Do educational and psychosocial interventions for adolescents with type 1 diabetes have beneficial effects on biological and psychosocial outcomes? (2) Are there types or features of interventions that have been shown to be more effective than others? (3) What evidence is there of the cost-effectiveness of interventions? METHODS: A search strategy was formulated, piloted and refined. Three journals were handsearched, 11 electronic databases were searched and personal contacts, flyers, conferences and websites were used to notify the research community of the review to access further literature. This process generated 10,535 abstracts, which, after screening, resulted in 367 articles identified for retrieval. This number was augmented by hand-searching, personal contact and exploding references, and a final total of 457 articles were scrutinised. Of these, 64 reports describing 62 studies were identified as empirical papers evaluating educational or psychosocial interventions. The relevant data were extracted from the papers and summary tables for each study were prepared. Where possible, effect sizes were computed for outcomes from studies that included a randomised control group (CG) and other relevant information. RESULTS: A descriptive analysis of the 62 studies was undertaken. Most studies (67.7%) were conducted in the USA and 41% were randomised controlled trials (RCTs), none of which were UK-based. Only 48% of the reports provided an explicit theoretical rationale for the intervention. The mean number of participants was 53.8. The studies took place in various settings, evaluated a variety of interventions, involved various interventionists, addressed various components and assessed the effects by a range of outcomes, including measures of metabolic control and psychological and behavioural outcomes. Follow-up assessments were relatively rare. RESULTS - THE EFFECTIVENESS OF INTERVENTIONS: The 25 RCTs were examined in more detail and three of the most effective were described in depth. Effect sizes could be calculated for 14 studies. The mean (pooled) effect size for psychosocial outcomes was 0.37 and 0.33 for glycated haemoglobin with outliers (0.08 without outliers), indicating that these interventions have small to medium beneficial effects on diabetes management outcomes. A narrative review of the 21 pre-post studies with no CG was performed, including evaluations of interventions conducted at summer camps, interventions for poorly controlled patients and educational interventions. All studies reported beneficial effects. RESULTS - COST-EFFECTIVENESS: Few studies addressed economic considerations associated with interventions, and the lack of information on costs and the diversity of outcomes included by investigators impeded cost- effectiveness comparisons. Shorter hospitalisation at diagnosis is at least as effective in achieving control and avoiding complications in adolescence as longer stays. Home care may result in improved outcomes but may not be cheaper than hospital care at diagnosis. Targeting poorly controlled subjects may reduce adverse events and hospitalisations and may be more cost-effective than generic interventions. There is a need for rigorous cost-effectiveness studies of educational and psychosocial interventions for adolescents with type 1 diabetes that include longer-term considerations. CONCLUSIONS: The following conclusions were drawn from this review: (1) Educational and psychosocial interventions have small to medium beneficial effects on various diabetes management outcomes. (2) Well-designed trials of such interventions are needed in the UK (no completed RCTs of educational or psychosocial interventions for adolescents with type 1 diabetes conducted in the UK were found). (3) The evidence, arising primarily from studies in the USA, provides a starting point for the design of interventions in the UK. (4) Quantitative and narrative analysis of the evidence suggested that interventions are more likely to be effective if they demonstrate the inter-relatedness of the various aspects of diabetes management. (ABSTRACT TRUNCATED)

Statistical assessment of the learning curves of health technologies.

Abstract: 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.

Clinical and cost-effectiveness of donepezil, rivastigmine and galantamine for Alzheimer's disease: a rapid and systematic review

Abstract: Background Alzheimer’s disease is the most common cause of dementia and is characterised by an insidious onset and slow deterioration The estimated prevalence of Alzheimer’s disease for a standard health authority (500,000 people) is about 3330 Current service involves a wide range of agencies, and drug therapy for some patients Objectives To provide a rapid and systematic review of the clinical effectiveness and cost-effectiveness of donepezil, rivastigmine and galantamine in the symptomatic treatment of people suffering from Alzheimer’s disease Methods A systematic review of the literature was undertaken Data sources Searches were made of electronic databases, including MEDLINE, EMBASE, The Cochrane Library, Database of Abstracts of Reviews of Effectiveness, NHS Economic Evaluation Database, National Research Register, Science Citation Index, BIOSIS, EconLit, MRC Trials database, Early Warning System, Current Controlled Trials, TOXLINE, Index of Scientific and Technical Proceedings, and Getting Easier Access to Reviews All sources were searched over the period covered by the databases up to March/July 2000 Biblioýraphies of related papers were assessed for relevant studies and experts were contacted for advice and peer review, and to identify additional published and unpublished references Manufacturer submissions to the National Institute for Clinical Excellence (NICE) were reviewed Study selection Studies were included if they fulfilled the following criteria Intervention: donepezil, rivastigmine or galantamine used to treat Alzheimer’s disease Participants: people diagnosed with Alzheimer’s disease who meet the criteria for treatment with donepezil, rivastigmine and galantamine Outcomes: measures assessing changes in cognition, function, behaviour and mood, quality of life (including studies assessing carer well-being and carer-input), and time to institutionalisation Design: systematic reviews of randomised controlled trials (RCTs) and RCTs comparing donepezil, rivastigmine or galantamine with placebo or each other or non-drug comparators were included in the review of effectiveness Economic studies of donepezil, rivastigmine or galantamine used to treat Alzheimer’s disease that included a comparator (or placebo) and both the costs and consequence (outcomes) of treatment were included in the review of cost-effectiveness Studies in non-English language, and abstracts and conference poster presentations of systematic reviews, RCTs and economic evaluations were excluded Two reviewers identified studies by independently screening study titles and abstracts, and then by examining the full text of selected studies to decide inclusion Data extraction and quality assessment Data extraction and quality assessment were undertaken by one reviewer and checked by a second reviewer, with any disagreements resolved through discussion The quality of RCTs was assessed using the Jadad scale and the quality of systematic reviews was assessed using criteria developed by the NHS Centre for Reviews and Dissemination The quality of economic evaluation studies was assessed by their internal validity (ie the methods used) using a standard checklist, and external validity (ie the generalisability of the economic study to the population of interest) using a series of relevant questions Data synthesis The clinical effectiveness and cost-effectiveness of donepezil, rivastigmine and galantamine were synthesised through a narrative review with full tabulation of results of all included studies In the economic evaluation, the reviewers assessed whether adjustments could be made to existing models to reflect the current situation in England and Wales Results Clinical effectiveness Donepezil – three systematic reviews and five RCTs (plus four studies from industry*) were found Results suggest that donepezil is beneficial when assessed using global and cognitive outcome measures Rivastigmine – three systematic reviews and five RCTs (plus two studies from industry*) were found Results suggest that rivastigmine is beneficial in terms of global outcome measures Galantamine – one systematic review and three RCTs (plus three studies from industry*) were found Results suggest that galantamine is beneficial in terms of global, cognitive and functional scales Summary of benefits It is difficult to quantify benefits from the evidence available in the literature Statistically significant improvements in tests such as ADAS-cog (Alzheimer’s Disease Assessment Scale cognitive subscale) may not be reflected in changes in daily life Costs/cost-effectiveness Nine economic studies were found, which could not be closely compared Donepezil – the five studies of donepezil produced a variety of cost-effectiveness estimates While the base cases showed increased effectiveness and were cost saving in two studies, they were more costly in the other three When sensitivity analyses are taken into consideration, estimates fluctuated more widely and there were, in some cases, conflicting results for sub-group analyses, thus casting doubt on the robustness of the estimates Rivastigmine – of the four rivastigmine studies, the oldest has been surpassed by more recent evaluations Cost-effectiveness ratios in two studies could not be extracted as the associated overall effectiveness was not reported and interpretation of the costs results alone is difficult due to the exclusion of drug therapy costs The fourth study found average net costs within the first year, but a cost saving at 2 years, but it was not clear whether the data presented could be translated into incremental cost-effectiveness ratios Galantamine – no published economic evaluations of galantamine were found For each drug there was a further economic analysis performed by industry* Economic implications of prescribing these drugs are uncertain The main issue is not drug costs per se, but the impact across different sectors Currently, this remains unclear since the financing and provision of care for patients with Alzheimer’s disease in England and Wales is complex and difficult to unravel Any cost savings would depend mainly on release of funds from residential care * Unpublished data, submitted as commercial in confidence Conclusions Implications On the basis of the current evidence, the implications of the use of donepezil, rivastigmine or galantamine to treat patients with Alzheimer’s disease are unclear The main issue is whether the modest benefits seen in the outcome measures used in the trials would translate into benefits significant to patients Future research Future research should include: development of quality-of-life instruments for patients and their carers; comparisons of benefits from drugs with those from other interventions; identification of those patients likely to benefit from drug treatment; development of protocols of treatment withdrawal if not beneficial; economic evaluations Ongoing research should provide valuable evidence

Home treatment for mental health problems: a systematic review.

Abstract: OBJECTIVE This review investigates the effectiveness of 'home treatment' for mental health problems in terms of hospitalisation and cost-effectiveness. For the purposes of this review, 'home treatment' is defined as a service that enables the patient to be treated outside hospital as far as possible and remain in their usual place of residence. METHODS - SYSTEMATIC LITERATURE SEARCH: 'Home treatment' excluded studies focused on day, residential and foster care. The review was based on Cochrane methodology, but non-randomised studies were included if they compared two services; these were only analysed if they provided evidence of the groups' baseline clinical comparability. METHODS - REVIEW OF ECONOMIC EVALUATIONS: Economic evaluations among the studies found were reviewed against established criteria. METHODS - IDENTIFICATION OF SERVICE COMPONENTS: A three-round Delphi exercise ascertained the degree of consensus among expert psychiatrists concerning the important components of community-based services that enable them to treat patients outside hospital. The identified components were used to construct the follow-up questionnaire. METHODS - FOLLOW-UP OF AUTHORS: As a supplement to the information available in the papers, authors of all the studies were followed up for data on service components, sustainability of programmes and service utilisation. METHODS - DATA ANALYSIS: The outcome measure was mean days in hospital per patient per month over the follow-up period. (1) Comparative analysis - compared experimental to control services. It analysed all studies with available data, divided into 'inpatient-control' and 'community-control' studies, and tested for associations between service components and difference in hospital days. (2) Experimental services analysis - analysed only experimental service data and tested for associations between service components and hospital days. RESULTS - SYSTEMATIC LITERATURE SEARCH: A total of 91 studies were found, conducted over a 30-year period. The majority (87) focused on people with psychotic disorders. RESULTS - REVIEW OF ECONOMIC EVALUATIONS: Only 22 studies included economic evaluations. They provided little conclusive evidence about cost-effectiveness because of problems with the heterogeneity of services, sample size, outcome measures and quality of analysis. RESULTS - DELPHI EXERCISE: In all, 16 items were rated as 'essential', falling into six categories: home environment; skill-mix; psychiatrist involvement; service management; caseload size; and health/social care integration. There was consensus that caseloads under 25 and flexible working hours over 7 days were important, but little support for caseloads under 15 or for 24-hour services, and consensus that home visiting was essential, but not on teams being 'explicitly dedicated' to home treatment. RESULTS - RESPONSE TO FOLLOW-UP: A total of 60% of authors responded, supplying data on service components and hospital days in most cases. Other service utilisation data were far less readily available. RESULTS - SERVICE CHARACTERISATION AND CLASSIFICATION: The services were homogeneous in terms of 'home treatment function' but fairly heterogeneous in terms of other components. There was some evidence for a group of services that were multidisciplinary, had psychiatrists as integrated team members, had smaller caseloads, visited patients at home regularly and took responsibility for both health and social care. This was not a cohesive group, however. RESULTS - SUSTAINABILITY OF SERVICES: The sustainability of home treatment services was modest: less than half the services whose authors responded were still identifiable. Services were more likely to be operational if the study had found them to reduce hospitalisation significantly. RESULTS - META-ANALYSIS: Meta-analysis with heterogeneous studies is problematic. The evidence base for the effectiveness of services identifiable as 'home treatment' was not strong. Within the 'inpatient-control' study group, the mean reduction in hospitalisation was 5 days per patient per month (for 1-year studies only). No statistical significance could be measured for this result. For 'community-control' studies, the reduction in hospitalisation was negligible. Moreover, the heterogeneity of control services, the wide range of outcome measures and the limited availability of data might have confounded the analysis. Regularly visiting at home and dual responsibility for health and social care were associated with reduced hospitalisation. Evidence for other components was inconclusive. Few conclusions could be drawn from the analysis of service utilisation data. RESULTS - LOCATION: Studies were predominately from the USA and UK, more of them being from the USA. North American studies found a reduction in hospitalisation of 1 day per patient per month more than European studies. North American and European services differed on some service components, but this was unlikely to account for this finding, particularly as no difference was found in their experimental service results. CONCLUSIONS - STATE OF RESEARCH: There is a clear need for further studies, particularly in the UK. The benefit of home treatment over admission in terms of days in hospital was clear, but over other community-based alternatives was inconclusive. CONCLUSIONS - NON-RANDOMISED STUDIES: Difficulties in systematically searching for non-randomised studies may have contributed to the smaller number of such studies found (35, compared with 56 randomised controlled trials). This imbalance was compounded by a relatively poor response rate from non-randomised controlled trial authors. Including them in the analysis had little effect. CONCLUSIONS - LIMITATIONS OF THIS REVIEW: A broad area was reviewed in order to avoid the problem of analysing by service label. While reviews of narrower areas may risk implying a homogeneity of the services that is unwarranted, the current strategy has the drawback that the studies cover a range of heterogeneous services. The poor definition of control services, however, is ubiquitous in this field, however reviewed areas are defined. Inclusion of mean data for which no standard deviations were available was problematic in that it prevented measuring the significance of the main findings. The lack of availability of this data, however, is an important finding, demonstrating the difficulty in seeking certainty in this area. Only days in hospital and cost-effectiveness were analysed here. The range and lack of uniformity of measures used in this field made meta-analysis of other outcomes impossible. It should be noted, however, that the findings pertain to these aspects alone. The Delphi exercise reported here was limited in being conducted only with psychiatrists, rather than a multidisciplinary panel. Its findings were used as a framework for the follow-up and analysis. Their possible bias should be borne in mind when considering them as findings in themselves. CONCLUSIONS - IMPLICATIONS FOR CLINICIANS: The evidence base for home treatment compared with other community-based services is not strong, although it does show that home treatment reduces days spent in hospital compared with inpatient treatment. There is evidence that visiting patients at home regularly and taking responsibility for both health and social care each reduce days in hospital. CONCLUSIONS - IMPLICATIONS FOR CONSUMERS: Services that visit patients at home regularly and those that take responsibility for both health and social care are likely to reduce time spent in hospital. Psychiatrists surveyed in this review also considered support for carers to be essential. The evidence from this review, however, was that few services currently have protocols for meeting carers' needs. CONCLUSIONS - RECOMMENDATIONS FOR RESEARCH AND COMMISSIONERS: A centrally coordinated research strategy, with attention to study design, is recommended. Studies should include economic evaluations that report health and social service utilisation. Service components should be collected and reported for both experimental and control services. Studies should be designed with adequate power and longer durations of follow-up and use comparable outcome measures to facilitate meta-analysis. Research protocols should be adhered to throughout the studies. It may be advisable that independent researchers conduct studies in future. It is no longer recommended that home treatment be tested against inpatient care, or that small, localised studies replicate existing, more highly powered studies.

Systematic reviews of wound care management: (3) antimicrobial agents for chronic wounds; (4) diabetic foot ulceration.

Abstract: Background Chronic wounds, including pressure sores, leg ulcers, diabetic foot ulcers and other kinds of wounds, healing by secondary intention are common in both acute and community settings. The prevention and treatment of chronic wounds includes many strategies, including the use of various wound dressings, bandages, antimicrobial agents, footwear, physical therapies and educational strategies. This review is one of a series of reviews, and focuses on the prevention and treatment of diabetic foot ulcers and the role of antimicrobial agents in chronic wounds in general. Objectives To assess the clinical- and cost-effectiveness of (1) prevention and treatment strategies for diabetic foot ulcers and (2) systemic and topical antimicrobial agents in the prevention and healing of chronic wounds. METHODS - DATA SOURCES: Nineteen electronic databases were searched, including MEDLINE, CINAHL, Embase and the Cochrane Library. Relevant journals, conference proceedings and bibliographies of retrieved papers were hand-searched. An expert panel was consulted. Methods - study selection Randomised and non-randomised trials with a concurrent control group, which evaluated any intervention for the prevention or treatment of diabetic foot ulcers, or systemic or topical antimicrobials for chronic wounds (diabetic foot ulcers, pressure ulcers, leg ulcers of various aetiologies, pilonidal sinuses, non-healing surgical wounds, and cavity wounds) and used objective measures of outcome such as: (1) development or resolution of callus; (2) incidence of ulceration (for diabetic foot ulcer prevention studies); (3) incidence of pressure sores (pressure sore prevention studies); (4) any objective measure of wound healing (frequency of complete healing, change in wound size, time to healing, rate of healing); (5) ulcer recurrence rates; (6) side-effects; (7) amputation rates (diabetic foot ulcer treatment studies); (8) healing rates and recurrence of disease, among others, for pilonidal sinuses. Studies reporting solely microbiological outcomes were excluded. Decisions on the inclusion of primary studies were made independently by two reviewers. Disagreements were resolved through discussion. Data were extracted by one reviewer into structured summary tables. Data extraction was checked independently by a second reviewer and discrepancies resolved by discussion. All included studies were assessed against a comprehensive checklist for methodological quality. INCLUDED STUDIES - DIABETIC FOOT ULCERS: Thirty-nine trials which evaluated various prevention and treatment modalities for diabetic foot ulcers: footwear (2), hosiery (1), education (5), screening and foot protection programme (1); podiatry (1) for the prevention of diabetic foot ulcers; and footwear (1), skin replacement (2), hyperbaric oxygen (2), ketanserin (3), prostaglandins (3), growth factors (5), dressings and topical applications (9), debridement (2) and antibiotics (2) for the treatment of diabetic foot ulcers. INCLUDED STUDIES - ANTIMICROBIALS: Thirty studies were included, 25 with a randomised design. There were nine evaluations of systemic antimicrobials and 21 of topical agents. Quality of studies The methodological and reporting quality was generally poor. Commonly encountered problems of reporting included lack of clarity about randomisation and outcome measurement procedures, and lack of baseline descriptive data. Common methodological weaknesses included: lack of blinded outcome assessment and lack of adjustment for baseline differences in important variables such as wound size; large loss to follow-up; and no intention-to-treat analysis. RESULTS - PREVENTION OF DIABETIC FOOT ULCERS: There is some evidence (1 large trial) that a screening and foot protection programme reduces the rate of major amputations. The evidence for special footwear (2 small trials) and educational programmes (5 trials) is equivocal. A single trial of podiatric care reported a significantly greater reduction in callus in patients receiving podiatric care. RESULTS - TREATMENT OF DIABETIC FOOT ULCERS: Total contact casting healed significantly more ulcers than did standard treatment in one study. There is evidence from 5 trials of topical growth factors to suggest that these, particularly platelet-derived growth factor, may increase the healing rate of diabetic foot ulcers. Although these studies were of relatively good quality, the sample sizes were far too small to make any definitive conclusions, and growth factors should be compared with current standard treatments in large, multicentre studies. Topical ketanserin increased ulcer healing rate in 2 studies, while systemic hyperbaric oxygen therapy reduced the rate of major amputations in 1 study. Preliminary research into the effects of iloprost and prostaglandin E1 (PGE1) on diabetic foot ulcer healing suggests possible benefits. However, good quality, large-scale confirmatory research is needed. (ABSTRACT TRUNCATED)

How to develop cost-conscious guidelines.

Abstract: Background Clinical guidelines, defined as 'systematically developed statements to assist both practitioner and patient decisions in specific circumstances', have become an increasingly familiar part of clinical care. Guidelines are viewed as useful tools for making care more consistent and efficient and for closing the gap between what clinicians do and what scientific evidence supports. Interest in clinical guidelines is international and has its origin in issues faced by most healthcare systems: rising healthcare costs; variations in service delivery with the presumption that at least some of this variation stems from inappropriate care; the intrinsic desire of healthcare professionals to offer, and patients to receive, the best care possible. Within the UK, there is ongoing interest in the development of guidelines and a fast-developing clinical-effectiveness agenda within which guidelines figure prominently. Over the last decade, the methods of developing guidelines have steadily improved, moving from solely consensus methods to methods that take explicit account of relevant evidence. However, UK guidelines have tended to focus on issues of effectiveness and have not explicitly considered broader issues, particularly cost. This report describes the methods developed to handle benefit, harm and cost concepts in clinical guidelines. It reports a series of case studies, each describing the development of a clinical guideline; each case study illustrates different issues in incorporating these different types of evidence. Health economics and clinical guidelines There has been no widely accepted successful way of incorporating economic considerations into guidelines. Unlike other areas of guideline development, there is little practical or theoretical experience to direct the incorporation of cost issues within clinical guidelines. However, the reasons for considering costs are clearly stated: "health interventions are not free, people are not infinitely rich, and the budgets of [health care] programmes are limited. For every dollar's worth of health care that is consumed, a dollar will be paid. While these payments can be laundered, disguised or hidden, they will not go away" (Eddy DM. A manual for assessing health practices and designing practice policies: the explicit approach. Philadelphia: American College of Physicians; 1992). Such opportunity costs are a universal phenomenon. In the USA it has been recommended that every set of clinical guidelines should include information on the cost implications of the alternative preventive, diagnostic, and management strategies for each clinical situation. The stated rationale was that this information would help potential users to evaluate better the potential consequences of different practices. However, it was acknowledged that "the reality is that this recommendation poses major methodological and practical challenges" (Institute of Medicine. Guidelines for clinical practice: from development to use. Washington: National Academy Press; 1992). Methods of developing clinical guidelines A guideline development process summarises the technical information about the value of treatments in a manner that makes them accessible and ready for use in clinical practice, alongside information on contextual issues. The requirement is that the presentation of costs and benefits of treatments is methodologically sound, robust and accessible. This report includes a summary of the current best practice in evidence-based guideline development, including recent methodological advances. The manner in which cost and cost-effectiveness concepts have been successfully incorporated into the guideline process is introduced. Guideline development case studies The 'cost-effectiveness' sections of 11 guidelines are reported to illustrate both the range of methods used and the nature of the recommendations reached by the guideline development groups when considering the profile of consequences of treatments including costs. These guidelines are broadly grouped as: (1) those using qualitative evidence summary methods; (2) those using quantitative evidence summary methods and addressing relatively narrow clinical questions; (3) those using quantitative evidence summary methods and addressing a broad clinical area; (4) a guideline based upon a decision analysis model. Conclusions The focus of this project was to explore the methods of incorporating cost issues within clinical guidelines. However, the process of reviewing evidence in guideline development groups is becoming increasingly sophisticated, not only in considerations of cost but also in review techniques and group process. At the outset of the project it was unclear how narrowly or broadly the concept of 'cost' could be considered. (ABSTRACT TRUNCATED)

Systematic reviews of wound care management: (5) beds; (6) compression; (7) laser therapy, therapeutic ultrasound, electrotherapy and electromagnetic therapy.

Abstract: Background: Chronic wounds such as leg ulcers, diabetic foot ulcers and pressure sores are common in both acute and community healthcare settings. The prevention and treatment of these wounds involves many strategies: pressure-relieving beds, mattresses and cushions are universally used as measures for the prevention and treatment of pressure sores; compression therapy in a variety of forms is widely used for venous leg ulcer prevention and treatment; and a whole range of therapies involving laser, ultrasound and electricity is also applied to chronic wounds. This report covers the final three reviews from a series of seven.

A rapid and systematic review of the clinical effectiveness and cost-effectiveness of debriding agents in treating surgical wounds healing by secondary intention.

Abstract: Background Most surgically sutured wounds heal without any complication. However, in some cases wound healing can be delayed due to the presence of infection or wound breakdown. This can result in the wounds becoming cavity wounds and thus necessitate healing by secondary intention. Other surgical wounds that are not sutured but left to heal by secondary intention include abscess cavities such as perianal abscesses or breast abscesses. Surgical wounds healing by secondary intention are thought to heal more slowly than wounds healing by primary intention, especially if infection is present or healing is compromised by factors such as decreased blood supply, poor nutritional status or a general suppression of the immune response. Such wounds may contain dead tissue and have a moderate or high level of exudate. Debridement involves the removal of devitalised, necrotic tissue or fibrin from a wound. There are many different methods that can be used to debride a wound, which are broadly classified as surgical/sharp, biosurgical, mechanical, chemical, enzymatic and autolytic. Although it is generally agreed that the management of surgical wounds which contain devitalised tissue and are healing by secondary intention requires debridement, it is not always clear as to what is the best method or agent to use. There is currently a large selection of products with debriding properties available on the market, which vary considerably in cost. It is important that the choice of both debriding method and product is based on the best scientific evidence available, taking into account both cost and effectiveness data. Objectives The review had two main objectives: (1) To determine the clinical effectiveness and cost-effectiveness of debriding agents in treating surgical wounds healing by secondary intention. (2) To evaluate the clinical effectiveness and cost-effectiveness of treating patients with surgical wounds healing by secondary intention at specialised wound care clinics as compared to conventional care. The review incorporated all debriding methods and any agent that is considered to have a debriding property. METHODS The following databases were searched using strategies designed specifically for each database: MEDLINE, EMBASE, CINAHL, HMIC (Health Management Information Consortium), CCTR via the Cochrane Library, the National Research Register (NRR), the NHS Economic Evaluation Database (NHS EED), and the Health Economic Evaluations Database (HEED). Additional references were identified through reviewing manufacturer and sponsor submissions made to NICE, the bibliographies of retrieved articles, and conferences proceedings on the Internet. Only randomised controlled trials (RCTs) or non-randomised controlled trials with concurrent controls and full economic evaluations were considered for inclusion. Only studies that evaluated some sort of debriding method or a specialised wound care clinic (a nurse with specialist training in wound care; care being provided by a multidisciplinary team; a fast-track referral system to other professions (e.g. dermatologist); or access to the latest health technology) were included in the review. Studies had to include participants with surgical wounds healing by secondary intention (e.g. cavity wounds, the consequences of wound dehiscence and abscesses) and report an objective measure of wound healing. Data were extracted by one reviewer and checked by a second. Quality assessment was conducted independently by two reviewers. Disagreements were resolved by consensus and, when necessary, by recourse to a third reviewer. The primary outcomes of interest were wound healing and cost. Results of data extraction and quality assessment were presented in structured tables and also as a narrative summary. In addition, where feasible, the results of individual studies were presented as forest plots. Studies were grouped according to the type of wound, debriding method and outcome measure used. RESULTS - CLINICAL EFFECTIVENESS: Seventeen trials met the inclusion criteria, all of which used the autolytic method of debridement. No studies were found that investigated sharp/surgical, biosurgical, mechanical, chemical or enzymatic debridement in the treatment of surgical wounds healing by secondary intention. No studies were found which investigated specialised wound care clinics that included the provision of care within a clinical setting (based in either primary or secondary care). The type of surgical wounds investigated by studies included in the review were those that had broken down postoperatively, perineal wounds resulting from proctolectomy or rectal excision, and those left open after pilonidal sinus excision or abscess incision, or wounds following a laparotomy. Four additional studies investigated treatment of postoperative wounds from toenail avulsions. (ABSTRACT TRUNCATED)

Systematic reviews of the effectiveness of day care for people with severe mental disorders: (1) acute day hospital versus admission; (2) vocational rehabilitation; (3) day hospital versus outpatient care.

Abstract: ***ACUTE DAY HOSPITAL VERSUS ADMISSION FOR ACUTE PSYCHIATRIC DISORDERS*** BACKGROUND: Inpatient treatment is an expensive way of caring for people with acute psychiatric disorders. It has been proposed that many of those currently treated as inpatients could be cared for in acute psychiatric day hospitals. OBJECTIVE: The aim of this review was to assess the effectiveness and feasibility of day hospital versus inpatient care for people with acute psychiatric disorders. METH

Issues in methodological research: perspectives from researchers and commissioners

Abstract: Objectives (1) Methodological research has few well-defined tools and processes analogous to those available for reviews and data collection in substantive health technology assessment. (2) This project was set up to obtain researchers' and others' views on the innovative projects on research methodology under the NHS Health Technology Assessment Programme and the usefulness of the research. (3) The study was intended to span both epistemological and management issues. (4) The following issues were explored: (a) the degree to which researchers would feel constrained by the "Cochrane" approach to systematic reviews when undertaking reviews of a methodological nature; (b) whether methodological projects may require exceptional design and management arrangements, in view of their novelty, subjectivity and complexity; (c) whether researchers would seek out other methods, in addition to undertaking reviews of argument, as a means of extending their understanding of methodological issues (there may be three categories of research methods in methodology: reviews of methodological argument, studies that use the literature as a source of data, and research that collects new primary data); (d) whether the Methodology Programme overall can be considered a "success". Methods (1) Telephone interviews were carried out on researchers (one senior and one junior per project), resulting in 35 interviews from 19 of the 20 target projects. (2) A qualitative postal survey was sent to 12 people who had played a key role in the development of the Methodology Programme; replies were received from six of them. (3) Analysis was undertaken of the hit rates for 29 projects on the NCCHTA website by the end of February and the end of May 1999, comparing those concerned with methodology (n = 10) and those concerned with other issues (n = 19). Results UNDERTAKING METHODOLOGICAL RESEARCH: VIEWS OF RESEARCHERS: This section summarises the views of 35 researchers who were interviewed by telephone. Results UNDERTAKING METHODOLOGICAL RESEARCH: VIEWS OF RESEARCHERS: (THE NATURE OF METHODOLOGICAL REVIEWS): (1) There was a reluctance among researchers to use the term "systematic review" in the methodological context. (2) Practical problems in undertaking methodological reviews were found at every stage of the research process. (a) In the initial search stage, preplanned strategies were difficult to maintain, owing to the need to respond to the problems of too few or too many references. (b) At the analysis stage, most studies were not formally weighted, but there was implicit weighting in researchers' views of their merits or relevance. (c) It was often only at the synthesis stage that researchers could see clearly what their study was able to do; iteration was frequently necessary at this point. (d) It was difficult to form simple conclusions and recommendations beyond summaries of what was known in the field. (e) Dissemination activities were most often directed to other health service researchers, with some attention to NHS policy makers and research commissioners. Results UNDERTAKING METHODOLOGICAL RESEARCH: VIEWS OF RESEARCHERS (THE NEED FOR FLEXIBILITY): (1) Few researchers had amended their topic or methods once their research was under way, although some had made minor changes to their original plan, generally to refine the topic to fit the time or data available. (2) Changing a topic was seen as inappropriate unless checked with funders, but changes in research methods were viewed as reasonable because questions might be refined in the light of information gained or early thinking. Results UNDERTAKING METHODOLOGICAL RESEARCH: VIEWS OF RESEARCHERS (THE QUESTION OF BIAS): (1) Few researchers considered that this kind of research could be undertaken or presented in a wholly unbiased way because of the need to assess the research studied. (2) Objectivity was nonetheless seen as something that researchers should strive towards. Efforts to do so included presenting data clearly, separating findings from discussion, covering all points of view, setting out their own assumptions and values, and testing their ideas on others known to have differing views. (3) The formal peer-review process was not seen to have made a difference here, primarily because of the stage at which referees become involved. Results UNDERTAKING METHODOLOGICAL RESEARCH: VIEWS OF RESEARCHERS (PROJECT MANAGEMENT--TIMING AND TIME MANAGEMENT): (1) A majority of projects were completed within 3 months of their due date. Those studies completed roughly on time were considered to have efficient junior researchers and good project management, including clear deadlines for different stages of the research. (2) Some studies had severe problems of time management. Too much time tended to be spent on collecting and reading the literature and the writing stage was not always well planned. Referees' comments were also slow in coming. (ABSTRACT TRUNCATED)

Extended scope of nursing practice: a multicentre randomised controlled trial of appropriately trained nurses and pre-registration house officers in pre-operative assessment in elective general surgery.

Abstract: Aim/ Principal Research Question: 1) To determine whether pre-operative assessment carried out by an appropriately trained nurse (ATN) is equivalent in quality to that carried out by a pre-registration house officer (PRHO). 2) To assess whether pre-assessments carried out by ATNs and PRHOs are equivalent in terms of cost. 3) To determine whether assessments carried out by ATNs are acceptable to patients. 4) To investigate the quality of communication between senior medical staff and ATNs. Factors of Interest: The extended role of appropriately trained nurses and pre-registration house officers in pre-operative assessment in elective general surgery. Methods: The study design was principally a prospective randomised equivalence trial but was accompanied by additional qualitative assessment of patient and staff perceptions, and an economic evaluation. The intervention consisted of a pre-operative assessment carried out by either an ATN or a PRHO. Of the patients who completed the study with a full evaluation, 926 patients were randomised to the PRHO arm of the trial and 948 to the ATN arm. Three ATNs took part in the study, one from each centre, together with a total of 87 PRHOs. Immediately following the initial assessment of a patient by a PRHO or an ATN, one of a number of clinical research fellows, all specialist registrars in anaesthetics, repeated the assessment and recorded it on a study form, together with a list of investigations required. The clinical research fellow then evaluated the competency of the initial assessor by comparing the quality of their assessment with their own. Any deficiencies in ordering of investigations and referral to other specialities were met in order to maximise patient care. Sample groups: All patients attending at one site for assessment prior to general anaesthetic for elective general, vascular, urological or breast surgery were potentially included in the study. Of 1907 patients who were randomised, 1874 completed the study with a full evaluation. The study was carried out at four NHS hospitals, three of which were teaching hospitals, in three NHS Trusts in Southampton, Sheffield and Doncaster. Outcome measures: Three areas of ATN and PRHO performance were judged separately, history taking, examination and ordering of tests, and each was graded into one of four categories, the most important of which was under-assessment, which would possibly have affected peri-operative management. In the case of ordering of tests, it was possible to have both over- and under-assessed a patient on different tests. Findings: The pre-operative assessments carried out by the ATNs were essentially equivalent to those performed by the PRHOs in terms of under-assessment that might possibly have affected peri-operative management, although there was variation between the ATNs in terms of the quality of history taking. This may be related to the low number of patients seen at one study site. PRHOs ordered significantly more unnecessary tests than the ATNs. The substitution of ATNs for PRHOs was calculated to be cost neutral. The results of the qualitative assessment showed that the use of ATNs for pre-operative assessment was acceptable to patients; however, there was no evidence that communication between senior medical staff and those carrying out pre-operative assessments was improved by their introduction. Conclusions: This study demonstrated no reason to inhibit the development of fully nurse-led pre-operative assessment, provided that the nurses are appropriately trained and maintain sufficient workload to retain skills. Implications for Further Research: Further research is needed in the following areas: 1) the extent and type of training needed for nurses undertaking the pre-operative assessment role 2) the use, costs and benefits of routine pre-operative testing.

A rapid and systematic review of the clinical effectiveness and cost-effectiveness of orlistat in the management of obesity

Abstract: Background The prevalence of obesity in developed societies is increasing Obesity is associated with an increased risk of co-morbidity, including cardiovascular disease and diabetes Following the withdrawal of fenfluramine and dexfenfluramine, interest has focused on a novel anti-obesity drug orlistat Objective To systematically assess the clinical effectiveness and cost-effectiveness of orlistat in the management of obesity METHODS - SEARCH STRATEGY: Nineteen electronic databases were searched from inception to June 2000 Additionally, Internet searches were carried out, bibliographies of retrieved articles were examined and submissions were received from the manufacturer of orlistat METHODS - INCLUSION AND EXCLUSION CRITERIA: Randomised controlled trials (RCTs) evaluating the effectiveness of orlistat used for weight loss or maintenance of weight loss in overweight or obese patients were eligible for inclusion Primary outcome measures were changes in body weight, fat content or fat distribution Secondary outcomes were changes in obesity-related risk-factor profiles, such as lipid levels, indicators of glycaemic control and blood pressure Studies recruiting people with eating disorders such as anorexia nervosa and bulimia nervosa were excluded METHODS - PROCESS OF STUDY SELECTION: Assessment of titles and abstracts was performed independently by two reviewers If either reviewer considered a reference to be relevant, the full paper was retrieved Full papers were assessed against the review selection criteria by two independent reviewers, and disagreements were resolved through discussion METHODS - DATA EXTRACTION: Data were extracted by one reviewer into structured summary tables and checked by a second reviewer Any disagreements about data were resolved by discussion METHODS - QUALITY ASSESSMENT: Each included trial was assessed against a comprehensive checklist for methodological quality Quality assessment was performed independently by two reviewers with disagreements resolved by discussion METHODS - METHODS OF ANALYSIS/SYNTHESIS: This report is a narrative summary, with results grouped according to study endpoint Statistical pooling was undertaken in groups of trials that were considered to be sufficiently similar METHODS - ESTIMATION OF QUALITY OF LIFE, COSTS AND COST-EFFECTIVENESS AND/OR COST PER QUALITY-ADJUSTED LIFE-YEAR: Relevant economic evaluations were identified from the search strategy described above Assessment of methodological quality was undertaken using principles outlined in published guidelines METHODS - COMPANY SUBMISSIONS: Data from company submissions were subject to the same selection and appraisal processes as other studies considered for inclusion in the review, except that only RCTs with a duration of at least 1 year were selected RESULTS - RESULTS OF THE SEARCH STRATEGY: Fourteen RCTs (including three company submissions) and two economic evaluations (including one company submission) were included in the review RESULTS - RESULTS OF THE QUALITY ASSESSMENT: Methodological quality of trials was moderate to good The main problems were lack of detail on methods used to produce true randomisation, small sample sizes in some cases and failure to use intention-to-treat analysis It is likely that maintenance of blinding was difficult due to adverse effects associated with the study medication RESULTS - EVIDENCE OF CLINICAL EFFECTIVENESS AND COST-EFFECTIVENESS: Most of the trials showed greater weight loss and better weight maintenance with orlistat compared to placebo at all endpoints (statistically significant differences for both outcomes) Orlistat 120 mg three times daily was the optimum regimen in terms of weight loss Most trials showed significant improvement in at least some lipid concentration parameters, and, in three RCTs, orlistat produced statistically significant reductions in blood pressure relative to placebo In obese patients with type 2 diabetes, orlistat resulted in a significantly greater weight loss at 1 year compared with placebo, and some parameters of glycaemic control and lipid concentration also showed significantly greater improvements compared with placebo The incidence of gastrointestinal adverse events was consistently higher in orlistat groups compared with placebo, and orlistat use was associated with lower serum levels of fat-soluble vitamins The cost per quality-adjusted life-year for orlistat was 45,881 UK pounds CONCLUSIONS - IMPLICATIONS FOR CLINICAL PRACTICE: Although many trials have demonstrated statistically significant differences between groups in terms of weight loss in favour of orlistat versus placebo, the differences may not always be of clinical significance The clinical significance of between-group differences for secondary outcomes may also be debatable Possible adverse effects should be taken into account when prescribing orlistat, particularly gastrointestinal effects (ABSTRACT TRUNCATED)

The role of radiography in primary care patients with low back pain of at least 6 weeks duration: a randomised (unblinded) controlled trial.

Abstract: Objectives To test the hypotheses that: (1) Lumbar spine radiography in primary care patients with low back pain is not associated with improved patient outcomes, including pain, disability, health status, sickness absence, reassurance, and patient satisfaction or belief in the value of radiography. (2) Lumbar spine radiography in primary care patients with low back pain is not associated with changes in patient management, including medication use, and the use of primary and secondary care services, physical therapies and complementary therapies. (3) Participants choosing their treatment group (i.e. radiography or no radiography) do not have better outcomes than those randomised to a treatment group. (4) Lumbar spine radiography is not cost-effective compared with usual care without lumbar spine radiography. Design A randomised unblinded controlled trial. Setting Seventy-three general practices in Nottingham, North Nottinghamshire, Southern Derbyshire, North Lincolnshire and North Leicestershire. Fifty-two practices recruited participants to the trial. Subjects Randomised arm: 421 participants with low back pain, with median duration of 10 weeks. Patient preference arm: 55 participants with low back pain, with median duration of 11 weeks. Intervention Lumbar spine radiography and usual care versus usual care without radiography. Main outcome measures Roland adaptation of the Sickness Impact Profile, visual analogue pain scale, health status scale, EuroQol, use of primary and secondary care services, and physical and complementary therapies, sickness absence, medication use, patient satisfaction, reassurance and belief in value of radiography at 3 and 9 months post-randomisation. Results Participants randomised to receive an X-ray were more likely to report low back pain at 3 months (odds ratio (OR) = 1.56; 95% confidence interval (CI), 1.02 to 2.40) and had a lower overall health status score (p = 0.02). There were no differences in health or functional status at 9 months. A higher proportion of participants consulted the general practitioner (GP) in the 3 months following an X-ray (OR = 2.72; 95% CI, 1.80 to 4.10). There were no differences in use of any other services, medication use or sickness absence at 3 or 9 months. No serious spinal pathology was identified in either group. The commonest X-ray reports were of discovertebral degeneration and normal findings. Many patients did not perceive their information needs were met within the consultation. Satisfaction with care was greater in the group receiving radiography at 9 months. Participants randomised to receive an X-ray were not less worried, or more reassured about serious disease causing their low back pain. Satisfaction was associated with meeting participants' information needs and reduced belief in the necessity for investigations for low back pain, including X-rays and blood tests. In both groups, at 3 and 9 months 80% of participants would choose to have an X-ray if the choice was available. Participants in the patient preference group achieved marginally better outcomes than those randomised to a treatment group, but the clinical significance of these differences is unclear. Lumbar spine radiography was associated with a net economic loss at 3 and 9 months. Conclusions Lumbar spine radiography in primary care patients with low back pain of at least 6 weeks duration is not associated with improved functioning, severity of pain or overall health status, and is associated with an increase in GP workload. Participants receiving X-rays are more satisfied with their care, but are not less worried or more reassured about serious disease causing their low back pain. CONCLUSIONS - RECOMMENDATIONS FOR FURTHER RESEARCH: Further work is required to develop and test an educational package that educates patients and GPs about the utility of radiography and provides strategies for identifying and meeting the information needs of patients, and the needs of patients and GPs to be reassured about missing serious disease. Guidelines on the management of low back pain in primary care should be consistent about not recommending lumbar spine radiography in patients with low back pain in the absence of red flags for serious spinal pathology, even if the pain has persisted for at least 6 weeks.

A rapid and systematic review of the clinical effectiveness and cost- effectiveness of paclitaxel, docetaxel, gemcitabine and vinorelbine in non-small-cell lung cancer

Abstract: BACKGROUND: The incidence of lung cancer is declining following a drop in smoking rates, but it is still the leading cause of death from cancer in England and Wales, with about 30,000 deaths a year. Survival rates for lung cancer are poor everywhere, but they appear to be better in the rest of the European Community and the USA than in the UK. Only about 5 per cent of people with lung cancer survive for 5 years, and nearly all of these are cured by surgery after fortuitously early diagnosis. At present, only a small proportion of patients (probably about 5 per cent) with non-small-cell lung cancer are being given chemotherapy. Some centres treat a greater proportion. OBJECTIVES: This review examines the clinical effectiveness and cost-effectiveness of four of the newer drugs - vinorelbine, gemcitabine, paclitaxel and docetaxel - used for treating the most common type of lung cancer (non-small-cell lung cancer). The first three drugs are used for first-line treatment, but at present docetaxel is used only after first-line chemotherapy has failed. METHODS: This report was based on a systematic literature review and economic modelling, supplemented by cost data. RESULTS - NUMBER AND QUALITY OF STUDIES: A reasonable number of randomised trials were found - three for docetaxel, six for gemcitabine, five for paclitaxel and 13 for vinorelbine. The quality of the trials was variable but good overall. There was a wide range of comparators. Some trials compared chemotherapy with best supportive care (BSC), which involves care that aims to control symptoms, with palliative radiotherapy if needed, but not to prolong life. Others compared the newer drugs against previous drugs or combinations. RESULTS - SUMMARY OF BENEFITS: The gains in duration of survival with the new drugs are modest - a few months - but worthwhile in a condition for which the untreated survival is only about 5 months. There are also gains in quality of life compared with BSC, because on balance the side-effects of some forms of chemotherapy have less effect on quality of life than the effects of uncontrolled spread of cancer. RESULTS - COSTS: The total cost to the NHS of using these new drugs in England and Wales might be about GBP 10 million per annum, but is subject to a number of factors. There would be non-financial constraints on any increase in chemotherapy for the next few years, such as staffing; the number of patients choosing to have the newer forms of chemotherapy is not yet known; and the costs of the drugs may fall, for example, as generic forms appear. RESULTS - COST PER LIFE-YEAR GAINED: The available data did not provide an entirely satisfactory basis for cost-effectiveness calculations. The main problem was the lack of direct comparisons of the new drugs. In order to strengthen the analysis, three different modelling approaches were used: pairwise comparisons using trial data; cost-minimisation analysis, as if all the new regimens were of equal efficacy; and cost-effectiveness analysis pooling the results of several trials with different comparators, giving indirect comparisons of the new drugs by using BSC as the common comparator. A number of different scenarios were explored through extensive sensitivity analysis in each model. Outcomes were expressed in incremental cost per life-year saved or incremental cost, versus BSC. There was insufficient evidence from which to derive cost per quality-adjusted life-year. In first-line treatment, vinorelbine, gemcitabine, and the lower-dose paclitaxel plus cisplatin combinations generally performed well against BSC under a range of different scenarios and especially when given as a maximum of 3 cycles. Incremental cost per life-year gained (LYG) versus BSC varied depending on scenario, but baseline figures based on trial data and protocols were: single-agent vinorelbine, pound 2194 per LYG; vinorelbine plus cisplatin, pound 5206; single-agent gemcitabine, pound 5690; gemcitabine plus cisplatin, pound 10,041; and paclitaxel plus cisplatin, pound 8537. In second-line chemotherapy, docetaxel gave a cost per LYG of pound 17,546, again well within the range usually accepted as cost-effective. However, in routine care, the impact of therapy would be regularly reviewed, and continuation would depend on response, side-effects, patient choice and clinical judgement. Chemotherapy would be stopped in non-responders, making chemotherapy more cost-effective. A 'real-life' scenario in which 60 per cent of patients receive only 1 or 2 cycles of chemotherapy gives much lower costs per LYG, with single-agent gemcitabine, single-agent vinorelbine, and paclitaxel plus platinum appearing to be cost-saving compared with BSC; the incremental cost of gemcitabine plus cisplatin would be pound 2478 per LYG, and of vinorelbine plus cisplatin, pound 2808. At the very least, gains in duration of survival were achieved without diminution of quality of life (at best, they improved quality) and with relatively low incremental cost. Comparisons among the individual drugs should be viewed with caution because they have had to be based on indirect comparisons. RESULTS - LIMITATIONS OF THE ANALYSIS: Each of the three models had limitations. The cost-effectiveness estimates from the pairwise comparisons were based on single studies. The cost-minimisation analysis assumed that the regimens have equal efficacy in practice. The cost-effectiveness analysis had to be based on pooling data from individual trials. The costs of BSC, inpatient stay and outpatient visits were from Scottish data. Median rather than mean data on duration of survival have been used in the analysis, because most of the trials reported only median data. Median survival and number of drug cycles were calculated by averaging across a number of studies, rather than being reliant on one particular study. The costs of the less expensive antiemetics cited in the trials were omitted. The use of more modern and costly antiemetics would have a modest detrimental effect on cost-effectiveness. In the absence of published data, an estimate was made of the cost of side-effects of chemotherapy, in particular hospital admissions, and applied to all the new regimens. In practice, admissions related to side-effects and their respective costs are likely to vary by regimen. CONCLUSIONS: The new drugs for non-small-cell lung cancer extend life by only a few months compared with BSC, but appear to do so without net loss in quality of life and at a cost per LYG that is much lower than for many other NHS activities. Depending on assumptions used, these new drugs range from being cost-effective, as conventionally accepted, to being cost-saving. CONCLUSIONS - IMPLICATIONS OF THE NEWER DRUGS: One of the present constraints on chemotherapy is availability of inpatient beds. The advent of newer and gentler forms of chemotherapy given on an outpatient basis would not only overcome this, but it would allow more patients to be treated. This might apply particularly to older patients. The treatment of more patients would increase workload for oncologists, cancer nurses and pharmacists. The Government has already announced increased expenditure on staff for cancer care. The previously pessimistic attitudes to chemotherapy in non-small-cell lung cancer are changing in the wake of the newer agents, and this shift is likely to increase referral. CONCLUSIONS - NEED FOR FURTHER RESEARCH: Recent advances in chemotherapy are welcome, but their effects remain small for patients with non-small-cell lung cancer. Much more research is needed into better drugs, better combinations, new ways of assessing the likelihood of response and especially direct comparisons between the new regimens. This research would be aided by having a greater proportion of patients involved in trials, but there will be infrastructure implications of increased participation.

General health status measures for people with cognitive impairment: learning disability and acquired brain injury.

Abstract: BACKGROUND Currently there is a wide range of health status measures that aim to assess general health status in people with cognitive impairment. However, the validity and/or applicability to this patient group are largely unknown. This has implications for the assessment of treatment outcomes and rehabilitation, for prognostic purposes, for planning services, and for determining the benefits and adverse effects of health technologies targeted at these patient groups. OBJECTIVES (1) To identify the general health status measures that have been validated in patients with cognitive impairment. (2) To assess the extent to which these measures have been validated. (3) To draw out the implications of the findings for the use of existing measures and for future primary research in this area. METHODS. SELECTION CRITERIA Studies that assessed general health status in people with cognitive impairment due to acquired brain injury (traumatic brain injury, cerebro-vascular accident or multiple sclerosis (MS)) or learning disability (LD) were included in the review. Studies that used general health status instruments measuring only one general health dimension, and studies that only featured participants with cognitive impairment due to dementia were excluded. METHODS. SEARCH STRATEGY A wide range of relevant databases were searched for studies on cognitive impairment, general health status measures, and validation of health status measures. A handsearch of general health status bibliographies was also conducted. Data were collected on the general health status measure used, the population characteristics, aims of the study, validity details, and conclusions. RESULTS The review includes data from 71 studies, reported in 83 separate publications. In total 34 different general health status measures were described in the 83 publications, with the Sickness Impact Profile (SIP) and the Short Form-36 (SF-36) the most frequently used measures (20 and 19 studies, respectively). These studies included a total of 98 instrument validations, 52 of which definitely or probably included people with cognitive impairment. Six measures were extensively validated (quality scores ranged from 0.25 to 0.5, on a scale from 0 to 1) in studies in which more than 50% of the respondents were people with cognitive impairment. A further three measures were also validated in studies in which more than 50% of the respondents were people with cognitive impairment, but their level of validation was more limited (quality scores ranged from 0.1 to 0.2). Five measures were validated in studies in which 20-50% of the respondents were cognitively impaired, which may limit their relevance to participants with cognitive impairment (quality scores ranged from 0.1 to 0.6). The SF-36 was also validated in two studies in which 20-50% of the respondents were cognitively impaired and the quality score was 0.3. Finally, nine of the measures were only validated in studies in which less than 20% of the respondents were cognitively impaired. For these measures it was unclear whether the findings applied to people with cognitive impairment. CONCLUSIONS Very few measures have been validated specifically for cognitively impaired respondents. Studies where at least 50% of the respondents were cognitively impaired generally showed poorer validity results compared with studies with fewer cognitively impaired persons, indicating that general health status measures designed for the general population are not automatically suitable for people with cognitive impairment. The few measures that were specifically developed for people with cognitive impairment also reported poor validity results. Therefore, there are no validated instruments available for use in cognitively impaired respondents; existing measures, specifically designed for use in these populations, should be used with caution. The most promising measure is the MS-Quality of Life Interview (MS-QLI) for MS patients. The MS-QLI was thoroughly validated in 300 MS patients and the results were good, except for the 'social function' subscale. However, only 20-50% of the respondents in this study had cognitive impairment. Most information on the validity of general health status measures was found in studies among people with LD. For these patients, six measures were found that have been validated in a populations where more than 50% of the respondents were cognitively impaired LD patients. CONCLUSIONS (1) Existing general health status measures should be used with caution in individuals with cognitive impairments. (2) There is no evidence to indicate the most suitable general health status measure for use in economic evaluations of cognitive impairment. (3) There is little evidence to support the validity of proxy assessments in cognitively impaired populations. (ABSTRACT TRUNCATED)

The cost-effectiveness of magnetic resonance imaging for investigation of the knee joint.

Abstract: OBJECTIVES: This study considered the role of magnetic resonance imaging (MRI) in the diagnosis of knee injuries in a district general hospital (DGH) setting. The principal objective was to identify whether the use of MRI had a major impact on the clinical management of patients presenting with chronic knee problems, in whom surgery was being considered, whether it reduced overall costs and whether it improved patient outcome. In addition, the research: (1) explored the 'diagnostic accuracy' of initial clinical investigation of the knee by an orthopaedic trainee, consultant knee specialist and consultant radiologist; (2) considered the variability and diagnostic accuracy of interpretations of knee MRI investigations between radiologists; (3) measured the strength of preference for the potential diagnostic/therapeutic impact of knee MRI (i.e. the avoidance of surgery). METHODS - RANDOMISED CONTROLLED TRIAL: The research was based on a single-centre randomised controlled trial conducted at Kent and Canterbury Hospital. Patients attending with knee problems in whom surgery was being considered were recruited from routine orthopaedic clinics. Most patients had been referred by their general practitioner. Patients were randomised to either investigation using an MRI scan (MRI trial arm) or investigation using arthroscopy (no-MRI trial arm). The study investigated the benefits of knee MRI at two levels: diagnostic/therapeutic impact (i.e. avoidance of surgery) and patient outcome (using the Short Form with 36 items and EQ-5D quality-of-life measurement instruments). Quality of life was assessed at baseline and at 6 and 12 months. Costs were assessed from the perspectives of the NHS and patients. All analyses were by intention to treat. METHODS - SUBSTUDIES (INVESTIGATION OF DIAGNOSTIC ACCURACY): For the investigation of diagnostic accuracy of initial clinical investigation, the sample comprised 114 patients recruited in a separate study conducted at St Thomas' Hospital. The sample was drawn from patients presenting at the Accident and Emergency Department with an acute knee injury. All study patients received an MRI scan, but initial diagnosis was made without access to the scan or the radiologist's report. After 12 months, all clinical notes and MRI scans of study patients were reviewed and a final 'reference standard' diagnosis for each patient was reached. Comparison was made between the diagnosis recorded by each clinician (i.e. orthopaedic trainee, knee specialist and consultant radiologist) and the reference diagnosis. METHODS - SUBSTUDIES (INVESTIGATION OF THE GENERALISABILITY OF RESULTS): For this substudy, the MRI images from 80 patients (recruited at St Thomas' Hospital) were interpreted independently by seven consultant radiologists at DGHs and the St Thomas' Hospital MRI radiologist. For each area of the knee, the level of agreement (measured using weighted kappa) between the responses of the eight radiologists and the reference standard diagnosis was assessed. METHODS - SUBSTUDIES (INVESTIGATION OF PREFERENCES): The investigation of potential patient preferences for the diagnostic/therapeutic impact of MRI was explored using a discrete choice conjoint measurement research design. Choices involved selecting between two alternative scenarios described using four attributes, and data were collected from 585 undergraduate sports science students and analysed using a random-effects probit model. RESULTS - RANDOMISED CONTROLLED TRIAL: The trial recruited 118 patients (59 randomly allocated to each arm). The two groups were similar in important respects at baseline. The central finding was of no statistically significant differences between groups in all measures of health outcome, although a trend in favour of the no-MRI group was observed. However, the use of MRI was found to be associated with a positive diagnostic/therapeutic impact: a significantly smaller proportion of patients in the MRI group underwent surgery (MRI = 0.41, no-MRI = 0.71; p = 0.001). There was a similar mean overall NHS cost for both groups. RESULTS - SUBSTUDIES (INVESTIGATION OF DIAGNOSTIC ACCURACY): The exploration of diagnostic accuracy found that, when compared to orthopaedic trainees (44% correct diagnoses) or to radiologists reporting an MRI scan (68% correct diagnoses), the accuracy rate was higher for knee specialists (72% correct diagnoses). RESULTS - SUBSTUDIES (INVESTIGATION OF THE GENERALISABILITY OF RESULTS): This generalisability study indicated that, in general terms, radiologists in DGHs provide accurate interpretations of knee MRI images that are similar to a radiologist at a specialist centre. The one area of the knee for which this did not hold was the lateral collateral ligament. RESULTS - SUBSTUDIES (INVESTIGATION OF PREFERENCES): The central finding for this substudy was that, on average and within the range specified, choices in this group of potential patients were not significantly influenced by variation in the chance of avoiding surgery. CONCLUSIONS - IMPLICATIONS FOR HEALTHCARE: The evidence presented in this report supports the conclusions that the use of MRI in patients presenting at DGHs with chronic knee problems in whom arthroscopy was being considered did not increase NHS costs overall, was not associated with significantly worse outcomes and avoided surgery in a significant proportion of patients. CONCLUSIONS - RECOMMENDATIONS FOR FURTHER RESEARCH (IN PRIORITY ORDER): (1) The trial data demonstrated that the use of MRI in patients with chronic knee problems reduced the need for surgery. However, the link between diagnostic processes and changes in health outcome is indirect and the finding of no-MRI-related effect on health outcome may, therefore, be a consequence of the limited power of the trial. Further research to confirm (or contradict) these findings would be valuable. (2) The investigation of diagnostic accuracy involved comparison with a reference diagnosis established by a panel of two clinical members of the research team. It would be interesting to explore the extent to which the results would differ using an external panel. (3) The result from the preference study, indicating that the potential diagnostic/therapeutic impact of knee MRI was not highly valued, is a surprising finding that would be important to explore in general public or patient populations. (4) The focus for the trial-based aspects of this research was the DGH and patients presenting with chronic knee problems who were being considered for surgery. Care should be taken in generalising from these results to other patient groups (e.g. acute knee injuries) or to other settings (e.g. specialist centres). Further clinical trials would be required in order to answer such questions.

Effectiveness of autologous chondrocyte transplantation for hyaline cartilage defects in knees: a rapid and systematic review.

Abstract: Background Proposed service Autologous chondrocyte transplantation (ACT) is a novel surgical approach used to treat full-thickness cartilage defects in knee joints. Small grafts of normal cartilage removed from the patient’s diseased joint are treated in a laboratory to obtain cartilage cells. These cells are cultured to expand the cell population and reimplanted a few weeks later into areas where cartilage is denuded by disease. The aim of this procedure is to restore normal cartilage to the ends of bones and thereby restore normal joint function. Epidemiology There are no reliable estimates of the prevalence of cartilage defects in the knee. Lesions are most likely to arise in sportsmen and women as a result of injury. Up to 20% of individuals sustaining a haemarthrosis following a knee injury may have cartilage damage. Objectives This systematic review of the available evidence was performed to: 1. Describe the types of knee disease for which ACT has been applied, the natural history and epidemiology of these conditions, and alternative treatment options 2. Determine long-term clinical outcomes following ACT and other surgical procedures for knee cartilage defects 3. Examine the economic evidence and consider the economic gains resulting from ACT. Methods To analyse the effectiveness of treatment and the resultant economic impact, a systematic review of the literature, involving a range of databases, was performed. In addition, contact was made with leading researchers and industry. Full details are described in the main report. Results Number and quality of studies and direction of evidence Of 46 identified reports, 17 met the criteria for inclusion in this review. Eight of the included reports were available as abstracts only. At least 2600 patients appear to have been treated with ACT. All included reports were case series with a variable length of follow-up. With one exception, all the studies reported improvement in patient status, usually over a follow-up period of less than 2 years. Summary of benefits The outcome of ACT surgery was rated as ‘good’ or ‘excellent’ by approximately 70% of patients 2 years after treatment. Approximately 16% of patients required further arthroscopic surgical procedures during follow-up, and treatment was judged to have failed in 3–7% of patients. For comparator treatments, the outcome was rated as ‘good’ or ‘excellent’ in 10–95% of patients 2 years after treatment. Economic review The reports of two studies, one based in the USA and the other in Sweden, included economic data. Neither study compared ACT with other treatments. Using data from these studies and other sources, it was estimated that ACT performed in the UK would cost £4667 or £8167 for cell culture and surgery, depending on which service provider was used for cell culture. Incremental cost over 2 years, when set against comparator treatments, was estimated to be £3771 or £7271 (base case) for cell culture, surgery and rehabilitation. Using the OsCell facility for cell culture (Robert Jones and Agnes Hunt Orthopaedic and District Hospital NHS Trust), this figure would be £3167. Conclusions The reported literature on ACT and comparators is subject to bias because of the inherent weaknesses of case series. In addition, the long-term impact of conventional surgical treatments or no surgical treatment is poorly documented. The cost-effectiveness analysis is similarly limited by the poverty of the effectiveness data on both ACT and comparators, the lack of long-term follow-up and the lack of empirical data for some of the parameters in the model used. Recommendations for research Further studies are required to: 1. Provide more accurate data on the occurrence of hyaline cartilage defects, including defects that arise acutely and those that are secondary to other types of knee injuries 2. Clarify the relationship of cartilage defects to clinical symptoms 3. Evaluate in detail the natural history of cartilage defects diagnosed by modern arthroscopic methods 4. Compare ACT with other treatments deemed appropriate, based on randomised trials currently in progress or planned 5. Examine, in prospective randomised trials, issues such as differences in outcome in patient subgroups (e.g. the suggested poor outcomes in patients with patellar defects), with patients followed for as long as possible 6. Address the deficiencies in evaluating the clinical outcomes of knee injury and incorporate measures of general health status 7. Consider study designs, other than randomised trials, that might be used to assess complex interventions such as those required in complex knee injuries.

An assessment of screening strategies for fragile X syndrome in the UK.

Abstract: Background Fragile X syndrome is an inherited form of learning disability that was defined in the late 1970s by cytogenetic detection of an associated fragile site on the X chromosome (Xq27.3). Cytogenetic estimates of the prevalence of fragile X syndrome were as high as 1 in 1039 males but have since been revised downwards. Fragile X syndrome is associated with few medical problems and the subtle physical features make clinical diagnosis difficult. The unusual pattern of inheritance, delineated in the 1980s, was explained once the fragile X syndrome gene (FMR1) had been identified in 1991. This gene contains a highly variable repeat of the nucleotide triplet, cytosine-guanine-guanine (CGG). Fragile X syndrome is caused by a large expansion of this CGG repeat (full mutation) that leads to silencing of the FMR1 gene so no gene product (FMRP) is made. This is the ultimate cause of the learning disability that, in males, is sufficient to preclude independent living. Family studies show that all individuals with a full mutation inherit it from a female (usually unaffected) who carries either a full mutation or a premutation, a smaller repeat expansion (approximately 55-200 repeats) that is unstable on female transmission. The chance of a premutation expanding to a full mutation is positively associated with the size of the repeat (approximately 95% by 90 repeats) but only for female transmissions. When a man transmits a premutation, it remains a premutation; his children are, therefore, unaffected by overt learning difficulties. The potential for population screening or systematic case-finding and extended family testing exists because every unaffected mother of an affected child has a detectable CGG repeat expansion. Reliable prenatal diagnosis is possible in males. Objectives To assess the feasibility and acceptability of population screening by addressing the following questions in the context of existing services for families with fragile X syndrome. (1) Is there a suitable test for all fragile X genotypes? (2) What are the UK population distribution of FMR1 repeat sizes, and the prevalence of full and premutations in both sexes? (3) What reliable information, in terms of the chance of an affected child, is available to women with premutations between 55 and 200 repeats? (4) What is the effect of a premutation on the person who carries it? (5) What information is available to women with intermediate alleles of 41 to 54-60 repeats? (6) How many affected people are diagnosed? (7) Given the practice of offering extended family testing (cascade testing), what is the population prevalence of 'as-yet-undiagnosed' female carriers of a full or premutation? What proportion of women at risk can be reached by cascade testing? (8) What are the costs of fragile X syndrome to an affected person and their family and to the NHS and society? (9) What is the attitude of families to the benefits and costs of a diagnosis of fragile X syndrome, and to the prospect of population screening? (10) What data are available from existing population screening programmes? (11) What alternatives to population screening exist and are these feasible? Methods A key aspect of the review process was to assemble a team with extensive first-hand experience of all aspects of fragile X syndrome, including affected families and the services they use, and a wide knowledge of the relevant literature. They had followed the critical discussions at all the biennial international workshops on fragile X syndrome, including a special session at the 7th International Workshop in 1995 at which an earlier (and substantially different) draft of this report was discussed. The biomedical literature review of 2429 papers was based on MEDLINE searches, extending to PsycINFO and BIDS for the psychological aspects of [fragile X syndrome] screening. Questionnaire-based information was obtained from the UK Fragile X Society and data were collected directly from all the regional clinical genetics centres in 1995 and 1998. Results Unlike cytogenetic approaches, DNA analysis can reliably determine the FMR1 CGG repeat number and detect full mutations; however, a combination of polymerase chain reaction and Southern blotting tests is required, which limits high throughput. There are UK population-based data on FMR1 repeat sizes of up to 60 repeats but insufficient to provide a reliable estimate of the prevalence of premutations (approximately 60-200 repeats). The few data and estimates in the literature of women carriers of the premutation range from 1 in 246 to 1 in 550. Two UK DNA-based estimates of the prevalence of males with the full mutation are 1 in 4090 (Coventry) and 1 in 5530 (Wessex). There are reasonable family-based data for the risk of expansion to a full mutation for the larger premutations but in the 50-69 repeat range the estimates are less secure. (ABSTRACT TRUNCATED)