Trevor Sheldon

Modelling in Ecomomic Evaluation: An Unavoidable Fact of Life

The role of modelling in economic evaluation is explored by discussing, with examples, the uses of models. The expanded use of pragmatic clinical trials as an alternative to models is discussed. Some suggestions for good modelling practice are made.

The treatment and prevention of obesity: a systematic review of the literature.

OBJECTIVE: To determine the effectiveness of interventions designed to prevent and treat obesity, and maintain weight loss. DESIGN: A systematic review of randomised controlled trials. SUBJECTS: Overweight and obese adults and children. MEASUREMENTS: Post-intervention changes in weight, fat content and fat distribution, measured relative to baseline. RESULTS: For obese children, family therapy and lifestyle modification appear to be effective in prevention and treatment, respectively. The effectiveness of interventions to prevent and treat obesity in adults remains unclear, although behavioural therapy and multicomponent strategies may be useful. Continued therapist contact appears to be useful for maintaining weight loss. Pharmacological interventions appear to be effective for up to 9 months, after which regain occurs. Surgery appears to be effective for the morbidly obese and gastric bypass is more effective than gastroplasty. In general, the methodological quality of studies was poor. CONCLUSION: Due to problems with methodological quality, it is recommended that research findings indicative of promising interventions are replicated. EDITORIAL NOTE: The full version of this review contained tabular and illustrative information that was too extensive and detailed to publish in the journal. This information is available on the CRD website (http://www.york.ac.uk/inst/crd/obesity.htm), or in the full CRD publication (contact first author).

Health effects of obstructive sleep apnoea and the effectiveness of continuous positive airways pressure: a systematic review of the research evidence.

Abstract Additional data from this article are available on the www.bmj.com/ Objective: To examine the research evidence for the health consequences of obstructive sleep apnoea and the effectiveness of continuous positive airways pressure. Design: A systematic review of published research, studies being identified by searching Medline (1966-96), Embase (1974-96), and CINAHL (Cumulative Index to Nursing and Allied Health Literature) (1982-95); scanning citations; and consulting experts. Studies in all languages were considered which either investigated the association between obstructive sleep apnoea in adults and key health outcomes or evaluated the effectiveness of treatment of obstructive sleep apnoea with continuous positive airways pressure in adults. Main outcome measures: Mortality, systematic hypertension, cardiac arrhythmias, ischaemic heart disease, left ventricular hypertrophy, pulmonary hypertension, stroke, vehicle accidents, measures of daytime sleepiness, and quality of life. Results: 54 epidemiological studies examined the association between sleep apnoea and health related outcomes. Most were poorly designed and only weak or contradictory evidence was found of an association with cardiac arrhythmias, ischaemic heart disease, cardiac failure, systemic or pulmonary hypertension, and stroke. Evidence of a link with sleepiness and road traffic accidents was stronger but inconclusive. Only one small randomised controlled trial evaluated continuous positive airways pressure. Five non-randomised controlled trials and 38 uncontrolled trials were identified. Small changes in objectively measured daytime sleepiness were consistently found, but improvements in morbidity, mortality, and quality of life indicators were not adequately assessed. Conclusions: The relevance of sleep apnoea to public health has been exaggerated. The effectiveness of continuous positive airways pressure in improving health outcomes has been poorly evaluated. There is enough evidence suggesting benefit in reducing daytime sleepiness in some patients to warrant large randomised placebo controlled trials of continuous positive airways pressure versus an effective weight reduction programme and other interventions. Key messages Obstructive sleep apnoea is claimed to be an important cause of premature death and disability There is increasing pressure to provide sleep services for the treatment of patients with sleep apnoea Epidemiological evidence suggests that sleep apnoea causes daytime sleepiness and possibly vehicle accidents Evidence for a causal association between sleep apnoea and other adverse health outcomes is weak There is a paucity of robust evidence for the clinical and cost effectiveness of continuous positive airways pressure in the treatment of most patients with sleep apnoea

Food elimination based on IgG antibodies in irritable bowel syndrome: a randomised controlled trial

Background: Patients with irritable bowel syndrome (IBS) often feel they have some form of dietary intolerance and frequently try exclusion diets. Tests attempting to predict food sensitivity in IBS have been disappointing but none has utilised IgG antibodies. Aims: To assess the therapeutic potential of dietary elimination based on the presence of IgG antibodies to food. Patients: A total of 150 outpatients with IBS were randomised to receive, for three months, either a diet excluding all foods to which they had raised IgG antibodies (enzyme linked immunosorbant assay test) or a sham diet excluding the same number of foods but not those to which they had antibodies. Methods: Primary outcome measures were change in IBS symptom severity and global rating scores. Non-colonic symptomatology, quality of life, and anxiety/depression were secondary outcomes. Intention to treat analysis was undertaken using a generalised linear model. Results: After 12 weeks, the true diet resulted in a 10% greater reduction in symptom score than the sham diet (mean difference 39 (95% confidence intervals (CI) 5–72); p =  0.024) with this value increasing to 26% in fully compliant patients (difference 98 (95% CI 52–144); p<0.001). Global rating also significantly improved in the true diet group as a whole (p = 0.048, NNT = 9) and even more in compliant patients (p = 0.006, NNT = 2.5). All other outcomes showed trends favouring the true diet. Relaxing the diet led to a 24% greater deterioration in symptoms in those on the true diet (difference 52 (95% CI 18–88); p = 0.003). Conclusion: Food elimination based on IgG antibodies may be effective in reducing IBS symptoms and is worthy of further biomedical research.

What's the evidence that NICE guidance has been implemented? Results from a national evaluation using time series analysis, audit of patients' notes, and interviews

Abstract Objectives To assess the extent and pattern of implementation of guidance issued by the National Institute for Clinical Excellence (NICE). Design Interrupted time series analysis, review of case notes, survey, and interviews. Setting Acute and primary care trusts in England and Wales. Participants All primary care prescribing, hospital pharmacies; a random sample of 20 acute trusts, 17 mental health trusts, and 21 primary care trusts; and senior clinicians and managers from five acute trusts. Main outcome measures Rates of prescribing and use of procedures and medical devices relative to evidence based guidance. Results 6308 usable patient audit forms were returned. Implementation of NICE guidance varied by trust and by topic. Prescribing of some taxanes for cancer (P < 0.002) and orlistat for obesity (P < 0.001) significantly increased in line with guidance. Prescribing of drugs for Alzheimers disease and prophylactic extraction of wisdom teeth showed trends consistent with, but not obviously a consequence of, the guidance. Prescribing practice often did not accord with the details of the guidance. No change was apparent in the use of hearing aids, hip prostheses, implantable cardioverter defibrillators, laparoscopic hernia repair, and laparoscopic colorectal cancer surgery after NICE guidance had been issued. Conclusions Implementation of NICE guidance has been variable. Guidance seems more likely to be adopted when there is strong professional support, a stable and convincing evidence base, and no increased or unfunded costs, in organisations that have established good systems for tracking guidance implementation and where the professionals involved are not isolated. Guidance needs to be clear and reflect the clinical context.

Cholesterol lowering and mortality: the importance of considering initial level of risk.

OBJECTIVE--To investigate the level of risk of death from coronary heart disease above which cholesterol lowering treatment produces net benefits. DESIGN--Meta-analysis of results of randomised controlled trials of cholesterol lowering treatments. METHODS--Published and unpublished data from all identified randomised controlled trials of cholesterol lowering treatments with six months or more follow up and with at least one death were included in the meta-analysis. The analyses were stratified by the rate of death from coronary heart disease in the control arms of the trials. MAIN OUTCOME MEASURES--Death from all causes, from coronary heart disease, and from causes other than coronary heart disease. RESULTS--In the pooled analysis, net benefit in terms of total mortality from cholesterol lowering was seen only for trials including patients at very high initial risk of coronary heart disease (odds ratio 0.74; 95% confidence interval 0.60 to 0.92). In a medium risk group no net effect was seen, and in the low risk group there were adverse treatment effects (1.22; 1.06 to 1.42). In a weighted regression analysis a significant (p < 0.001) trend of increasing benefit with increasing initial risk of coronary heart disease was shown. Raised mortality from causes other than coronary heart disease was seen in trials of drug treatment (1.21; 1.05 to 1.39) but not in the trials of non-drug treatments (1.02; 0.88 to 1.19). Cumulative meta-analysis showed that these results seem to have been stable as new trials appeared. CONCLUSION--Currently evaluated cholesterol lowering drugs seem to produce mortality benefits in only a small proportion of patients at very high risk of death from coronary heart disease. Population cholesterol screening could waste resources and even result in net harm in substantial groups of patients. Overall risk of coronary heart disease should be the main focus of clinical guidelines, and a cautious approach to the use of cholesterol lowering drugs should be advocated. Future trials should aim to clarify the level of risk above which treatment is of net benefit.

Selective serotonin reuptake inhibitors: meta-analysis of efficacy and acceptability.

OBJECTIVE--To examine the evidence for using selective serotonin reuptake inhibitors instead of tricyclic antidepressants in the first line treatment of depression. DESIGN--Meta-analysis of 63 randomised controlled trials comparing the efficacy and acceptability of selective serotonin reuptake inhibitors with those of tricyclic and related antidepressants. MAIN OUTCOME MEASURES--Improvement in mean scores on Hamilton depression rating scale for 53 randomised controlled trials. Pooled drop out rates from the 58 trials which reported drop out by treatment group. RESULTS--Among the 20 studies reporting standard deviation for the Hamilton score no difference was found in efficacy between serotonin reuptake inhibitors and tricyclic and related antidepressants (standardised mean difference 0.004, 95% confidence interval -0.096 to 0.105). The difference remained insignificant when the remaining 33 studies that used the 17 item and 21 item Hamilton score were included by ascribing weighted standard deviations. The odds ratio for drop out rate in patients receiving serotonin reuptake inhibitors compared with those receiving tricyclic antidepressants was 0.95 (0.86 to 1.07). Similar proportions in both groups cited lack of efficacy as the reason for dropping out but slightly more patients in the tricyclic group cited side effects (18.8% v 15.4% in serotonin reuptake group). CONCLUSIONS--Routine use of selective serotonin reuptake inhibitors as the first line treatment of depressive illness may greatly increase cost with only questionable benefit.

Screening and case-finding instruments for depression: a meta-analysis

Background: Screening and case-finding has been proposed as a simple, quick and cheap method to improve the quality of care for depression. We sought to establish the effectiveness of screening in improving the recognition of depression, the management of depression and the outcomes of patients with depression. Methods: We performed a Cochrane systematic review of randomized controlled trials conducted in nonmental health settings that included case-finding or screening instruments for depression. We conducted a meta-analysis and explored heterogeneity using meta-regression techniques. Results: Sixteen studies with 7576 patients met our inclusion criteria. We found that the use of screening or case-finding instruments were associated with a modest increase in the recognition of depression by clinicians (relative risk [RR] 1.27, 95% confidence interval [CI] 1.02 to 1.59). Questionnaires, when administered to all patients and the results given to clinicians irrespective of baseline score, had no impact on recognition (RR 1.03, 95% CI 0.85 to 1.24). Screening or case finding increased the use of any intervention by a relative risk of 1.30 (95% CI 0.97 to 1.76). There was no evidence of influence on the prescription of antidepressant medications (RR 1.20, 95% CI 0.87 to 1.66). Seven studies provided data on outcomes of depression, and no evidence of an effect was found (standardized mean difference –0.02, 95% CI –0.25 to 0.20). Interpretation: If used alone, case-finding or screening questionnaires for depression appear to have little or no impact on the detection and management of depression by clinicians. Recommendations to adopt screening strategies using standardized questionnaires without organizational enhancements are not justified.

Routinely administered questionnaires for depression and anxiety: systematic review

Abstract Objectives: To examine the effect of routinely administered psychiatric questionnaires on the recognition, management, and outcome of psychiatric disorders in non-psychiatric settings. Data sources: Embase, Medline, PsycLIT, Cinahl, Cochrane Controlled Trials Register, and hand searches of key journals. Methods: A systematic review of randomised controlled trials of the administration and routine feedback of psychiatric screening and outcome questionnaires to clinicians in non-psychiatric settings. Narrative overview of key design features and end points, together with a random effects quantitative synthesis of comparable studies. Main outcome measures: Recognition of psychiatric disorders after feedback of questionnaire results; interventions for psychiatric disorders; and outcome of psychiatric disorders. Results: Nine randomised studies were identified that examined the use of common psychiatric instruments in primary care and general hospital settings. Studies compared the effect of the administration of these instruments followed by the feedback of the results to clinicians, with administration with no feedback. Meta-analytic pooling was possible for four of these studies (2457 participants), which measured the effect of feedback on the recognition of depressive disorders. Routine administration and feedback of scores for all patients (irrespective of score) did not increase the overall rate of recognition of mental disorders such as anxiety and depression (relative risk of detection of depression by clinician after feedback 0.95, 95% confidence interval 0.83 to 1.09). Two studies showed that routine administration followed by selective feedback for only high scorers increased the rate of recognition of depression (relative risk of detection of depression after feedback 2.64, 1.62 to 4.31). This increased recognition, however, did not translate into an increased rate of intervention. Overall, studies of routine administration of psychiatric measures did not show an effect on patient outcome. Conclusions: The routine measurement of outcome is a costly exercise. Little evidence shows that it is of benefit in improving psychosocial outcomes of those with psychiatric disorder managed in non-psychiatric settings.

A systematic review of compression treatment for venous leg ulcers

Abstract Objective: To estimate the clinical and cost effectiveness of compression systems for treating venous leg ulcers. Methods: Systematic review of research. Search of 19 electronic databases including Medline, CINAHL, and Embase. Relevant journals and conference proceedings were hand searched and experts were consulted. Main outcome measures: Rate of healing and proportion of ulcers healed within a time period. Study selection: Randomised controlled trials, published or unpublished, with no restriction on date or language, that evaluated compression as a treatment for venous leg ulcers. Results: 24 randomised controlled trials were included in the review. The research evidence was quite weak: many trials had inadequate sample size and generally poor methodology. Compression seems to increase healing rates. Various high compression regimens are more effective than low compression. Few trials have compared the effectiveness of different high compression systems. Conclusions: Compression systems improve the healing of venous leg ulcers and should be used routinely in uncomplicated venous ulcers. Insufficient reliable evidence exists to indicate which system is the most effective. More good quality randomised controlled trials in association with economic evaluations are needed, to ascertain the most cost effective system for treating venous leg ulcers. Key messages Compression treatment increases the healing of ulcers compared with no compression High compression is more effective than low compression but should only be used in the absence of significant arterial disease No clear differences in the effectiveness of different types of compression systems (multilayer and short stretch bandages and Unnas boot) have been shown Intermittent pneumatic compression appears to be a useful adjunct to bandaging Rather than advocate one particular system, the increased use of any correctly applied high compression treatment should be promoted