James Mason

Systems for grading the quality of evidence and the strength of recommendations II: Pilot study of a new system

BackgroundSystems that are used by different organisations to grade the quality of evidence and the strength of recommendations vary. They have different strengths and weaknesses. The GRADE Working Group has developed an approach that addresses key shortcomings in these systems. The aim of this study was to pilot test and further develop the GRADE approach to grading evidence and recommendations.MethodsA GRADE evidence profile consists of two tables: a quality assessment and a summary of findings. Twelve evidence profiles were used in this pilot study. Each evidence profile was made based on information available in a systematic review. Seventeen people were given instructions and independently graded the level of evidence and strength of recommendation for each of the 12 evidence profiles. For each example judgements were collected, summarised and discussed in the group with the aim of improving the proposed grading system. Kappas were calculated as a measure of chance-corrected agreement for the quality of evidence for each outcome for each of the twelve evidence profiles. The seventeen judges were also asked about the ease of understanding and the sensibility of the approach. All of the judgements were recorded and disagreements discussed.ResultsThere was a varied amount of agreement on the quality of evidence for the outcomes relating to each of the twelve questions (kappa coefficients for agreement beyond chance ranged from 0 to 0.82). However, there was fair agreement about the relative importance of each outcome. There was poor agreement about the balance of benefits and harms and recommendations. Most of the disagreements were easily resolved through discussion. In general we found the GRADE approach to be clear, understandable and sensible. Some modifications were made in the approach and it was agreed that more information was needed in the evidence profiles.ConclusionJudgements about evidence and recommendations are complex. Some subjectivity, especially regarding recommendations, is unavoidable. We believe our system for guiding these complex judgements appropriately balances the need for simplicity with the need for full and transparent consideration of all important issues.

A systematic review of foot ulcer in patients with Type 2 diabetes mellitus. I: prevention

Aim To evaluate the role of preventative strategies in reducing foot ulcers in patients with Type 2 diabetes mellitus, both in the general population and those identified to be at a raised risk.

Effect of population screening and treatment for Helicobacter pylori on dyspepsia and quality of life in the community: a randomised controlled trial

BACKGROUND Infection with Helicobacter pylori is the main cause of peptic-ulcer disease. Treatment of this infection might lower the prevalence of dyspepsia in the community and improve quality of life. We investigated this possibility in a double-blind randomised controlled trial. METHODS Individuals aged 40-49 years were randomly selected from the lists of 36 primary-care centres. A researcher interviewed participants with a validated dyspepsia questionnaire and the psychological general wellbeing index (PGWB). H. pylori status was assessed by the carbon-13-labelled urea breath test. Infected participants were randomly assigned active treatment (omeprazole 20 mg, clarithromycin 250 mg, and tinidazole 500 mg, each twice daily for 7 days) or identical placebo. Participants were followed up at 6 months and 2 years. FINDINGS Of 32,929 individuals invited, 8455 attended and were eligible; 2324 were positive for H. pylori and were assigned active treatment (1161) or placebo (1163). 1773 (76%) returned at 2 years. Dyspepsia or symptoms of gastro-oesophageal reflux were reported in 247 (28%) of 880 in the treatment group and 291 (33%) of 871 in the placebo group (absolute-risk reduction 5% [95% CI 1-10]). H. pylori treatment had no significant effect on quality of life (mean difference in PGWB score between groups 0.86 [-0.33 to 2.05]). INTERPRETATION Community screening and treatment for H. pylori produced only a 5% reduction in dyspepsia. This small benefit had no impact on quality of life.

Psychiatric illness and mortality after hip fracture

People with dementia or delirium have increased mortality in the 6 months after hip fracture, but depression might take longer to have an effect. We assessed the psychiatric status of 731 participants with hip fracture and analysed the effect of psychiatric illness on mortality during the next 2 years. We found that dementia, delirium, and depression all increased the risk of mortality (p<0.0001, p<0.0001, and p=0.0359, respectively), and that mortality differed significantly between hospitals (p=0.0003). We suggest that psychiatric interventions should be asssessed in hip-fracture patients with adequate follow up of outcome measures.

The cost-effectiveness of population Helicobacter pylori screening and treatment: a Markov model using economic data from a randomized controlled trial

Economic models have suggested that population Helicobacter pylori screening and treatment may be a cost‐effective method of reducing mortality from gastric cancer. These models are conservative as they do not consider that the programme may reduce health service peptic ulcer and other dyspepsia costs. We have evaluated the economic impact of population H. pylori screening and treatment over 2 years in a randomized controlled trial and have incorporated the results into an economic model exploring the impact of H. pylori eradication on peptic ulcer disease and gastric cancer.

Educational outreach in diabetes to encourage practice nurses to use primary care hypertension and hyperlipidaemia guidelines (EDEN): a randomized controlled trial

Objective  To determine the effectiveness of specialist nurse delivered education in primary care to improve control of hypertension and hyperlipidaemia in patients with diabetes.

Publication Bias in Clinical Trials and Economic Analyses

SummaryPublication bias is an established notion in the clinical literature; essentially, large studies or positive results are more likely to find their way into the public domain than small studies or negative results. Meta-analysis presents a focus for the problems of publication bias, seeking to summarise the evidence in a particular therapeutic area by retrieving and analysing all available clinical studies.Economic analyses are also vulnerable to publication bias, and at 3 levels: first, in the health-outcomes data available for modelling (resulting from publication bias in the clinical literature); second, in the motivations for conducting an economic analysis; and third, in repeating the process of seeking publication.

Cost-per-QALY League Tables

SummaryIt has become common for analysts to present the findings of cost-utility analyses in cost per quality-adjusted life-year (QALY) league tables or rankings. These purport to s how the relative value-for-money of different healthcare technologies. Concomitantly, there is an increasing market for cost-effectiveness data worldwide.However, the practice of constructing league tables has drawn criticism. Claims of inappropriate comparisons, and poor and flawed methodology have been made. How should decision-makers view cost/QALY league tables? In future, published league tables will need 10 be more informative and thus, by necessity, complex. The principal obstacle to informing health policy- makers with economic analysis is the lack of appropriate outcome data. From this follows uncertainty as to what represents acceptable value-for-money in healthcare purchasing. Thus, the long term objective must be to obtain valid assessments of the value of current and new health service activities. It is in this context that league tables may eventually be most helpful. More immediately, a strategy is required to help decision-makers to prioritise resources rationally with incomplete information.

Designing evaluations of interventions to change professional practice.

The design and interpretation of experimental studies to examine the effectiveness and efficiency of implementation strategies intended to change professional practice are gaining increasing attention. It has been argued that variations of the simple randomised design are most appropriate in this setting. The principles of block designs and their applicability in this field are reviewed critically, as are the choice of outcomes and approaches to economic analysis. We conclude that more complex designs are not superior per se, and that the design, choice of implementation method and topic, and analysis of such experiments should reflect the circumstances of the study.

The DiSC assay. A cost-effective guide to treatment for chronic lymphocytic leukemia?

The differential staining cytotoxicity (DiSC) assay involves in vitro drug panel testing against patient tumor cells to identify optimal therapy. This observational study investigated whether DiSC assay guided treatment could improve outcome in patients with chronic lymphocytic leukemia. A cohort of 178 patients were categorized either as sensitive to drugs in vitro and receiving a sensitive drug in vivo, sensitive in vitro but not treated with a sensitive drug, or having disease resistant to all drugs tested in vitro. Response and survival for these patient categories were compared using multivariate regression techniques. Patients receiving a sensitive drug, compared with those who though having sensitivity did not, had a higher remission rate (odds ratio, 6.5; 95% CI, 2.91-14.53) and reduced death rate (hazard ratio, 0.29; 95% CI, 0.16-0.53). Having adjusted for all known confounding factors, the results suggest that in vitro drug sensitivity is an important independent prognostic variable to include in future trials, and that the DiSC assay may be a cost-effective use of health resources: the estimated incremental cost-effectiveness was 1,470 Pounds per life-year gained. A randomized controlled trial is required to confirm the benefit and estimate reliably the potential impact of assay-guided choice of therapy.