What is a review? An article which looks at a question or subject and seeks to summarise and bring together evidence on a health topic. Ask What is a review? Ask for examples update prescribers journal drug and therapeutic journal bmj medical textbooks medicine

Objectives of session Know what is special about a systematic review know what meta-analysis is have a check list for looking at systematic reviews first slide

What is a systematic review? In a review a question must be posed, a target population of information sources identified and accessed, appropriate information obtained from that population in an unbiased fashion, and conclusions derived. the methodology will be explicit and reproducible. Ask what is a systematic review emphasise that it is a piece of rigorous research with all of the steps involved in primary research. IT IS REPRODUCIBLE Perhaps draw attention to the otitis media meta analysis and the explicit steps taken to ensure all trials were found and the the trials were graded blind to the author and to the journal in which they were published

check list of data sources medline cochrane other medical and paramedical databases foreign language literature Grey literature.(theses, internal reports, non-peer reviewed journals, pharmaceutical industry files references other unpublished sources raw data from published trials flip chart - derive list talk about publication bias Negative results

Why bother with systematic reviews? To reduce large volumes of information to bite size pieces. To allow decision makers to integrate critical pieces of biomedical information. An efficient scientific technique which is often less costly than embarking on new research. The generalisability of scientific findings can be established. Look at the Thrombolysis meta analysis Look at how early the benefits of thrombolysis were obvious To attempt to eliminate reviewer bias: 1987(second edition Oxford Textbook of medicine) A distinguished cardiologist advised….”The clinical benefits of thrombolysis (in treating patients with MI) whether expressed as improved patient survival or preservation of left ventricular function, remain to be established.” This appeared 4 years after a review by Yusuf showed the clear benefits of thrombolysis. Maybe look at the lignocaine review

Why bother with systematic reviews? To assess the consistency of relationships. To explain data inconsistencies and conflicts in data. Increased power. Increased precision in estimates of effect. To reduce random and systematic errors. In the thrombolysis meta analysis Iv streptokinase could have been shown to be life saving 20 years ago ISIS2 GISSI no change in evidence of efficacy but slightly narrowed the confidence intervals. more than 10000 patients in each trial.

What on earth is Meta-analysis? A systematic review where there is statistical analysis of data from the trials included in the review.

What can go wrong with a systematic review? Problem formulation Is the question clearly focused? Study identification Is the search for relevant studies thorough? Study selection Are the inclusion criteria appropriate? Publication bias

What can go wrong with a systematic review? Appraisal of studies Is the validity of included studies adequately assessed? Data collection Is missing information obtained from investigators? Data synthesis How sensitive are the results to changes in the way the review is done? Blind assessment of studies Ask how sensitive the results are to changes in the way that the review is done. Test how robust the results of the review are. change inclusion criteria include or exclude trials with some ambiguity as to whether they meet the inclusion criteria Exclude unpublished studies exclude studies of lower methodological quality Reanalyse the data using different statistical approaches

What can go wrong with a systematic review? Interpretation of results Do the conclusions flow from the evidence that is reviewed? Are recommendations linked to the strength of the evidence? Are judgements about preferences (values attached to different outcomes) explicit? If there is "no evidence of effect" is caution taken not to interpret this as "evidence of no effect"? Are subgroup analyses interpreted cautiously? conclusions do not exceed the evidence Look at levels of evidence: Health care interventions involve costs and risk of harm as well as expectations of benefit practice recommendations require judgements about preferences (the values attached to different outcomes) If conclusions involve such judgements this should be clearly stated. e.g. HRT

Levels of evidence for treatment Level I The lower limit of the confidence interval for the effect of treatment from a systematic review of randomised controlled trials exceeded the clinically significant benefit. Level II The lower limit of the confidence interval for the effect of treatment from a systematic review of randomised controlled trials fell below the clinically significant benefit (but the point estimate of its effect was at or above the clinically significant benefit) Level III Non-randomised concurrent cohort studies Level IV Non-randomised historical cohort studies Level V Case series

The Hierarchy of Evidence Systematic reviews and meta-analyses Randomised controlled trials with definite results Randomised controlled trials with non-definite results Cohort Studies Case control studies Cross sectional surveys Case reports