1. Conducting systematic reviews for development of clinical guidelines 8 August 2013 Professor Mike Clarke m.clarke@QUB.ac.uk

2. What is a systematic review? What do you think it is?

3. Systematic reviewing  Formulating a clear question for the review  Stating objectives and eligibility criteria  Identifying (all) potentially eligible studies  Applying eligibility criteria  Assembling most complete dataset feasible  Analysing the dataset, using statistical synthesis and sensitivity analyses, if appropriate and possible  Preparing a structured report  Updating the review

4. Formulating the question for a review

5. Choosing the studies to include in a review depends on the question to be answered

6. Do green sweets make people happy?

7. Measuring the happiness of everyone who eats green sweets

8. Getting some of you to eat a green sweet and then measuring your happiness

9. Measuring the happiness of a random sample of those who ate a green sweet, and those who did not

10. Getting some of you to eat a green sweet and some of you not to, and then measuring your happiness

11. Do green sweets make people happy?

13. Formulating the question for a review

15. Question formulation You need a clear question. It might change during the planning of the review, but you hope it won’t change during its conduct. Each word in the question is important. Do the words narrow or broaden your review? Will other people think each word or phrase means the same thing as you think it means? Each word in the question can be expanded in the eligibility criteria for the review.

16. Setting the eligibility criteria

17. Participants Interventions Outcome measures Study designs

19. Eligibility criteria The eligibility criteria provide the rules for what should and should not be included in your review. Think about the types of study that might have been done and decide if you would want them in your review. The results of a study must not influence your decision to include it. The eligibility criteria help you avoid having to make decisions about an unexpected study, after you know its results. The eligibility criteria don’t always have to match your question perfectly, you might be able to borrow from other areas.

20. Searching

22. What to consider when searching What terms to search for? What types of database to search? What countries? What languages? What time period?

23. Planning the search terms Divide the review into the eligibility components  Participants  Interventions (including comparator)  Outcomes  Study designs The database you are searching will try to help you by only showing the things that you ask for. It might hide millions of other things.

24. Choosing the search terms In listing terms for each component, consider:  Synonyms (from different times and places)  Other words and phrases that are related to what you’re interested in  Words that are broader  Words that are more focused  Index terms or keywords

25. Combining search terms Two main ways to link terms  AND (decreases the number of hits, requires every item to be present)  OR (increases the number of hits, requires any of the items to be present)  Try to avoid NOT (it might remove records that actually are eligible)

26. Combining the components Within the component, use OR to combine the terms and then use AND to combine the components. But...  Do you need all the components?  Are you confident that you have all the terms within each component?  Which component is least likely to be relevant?  Which component is most likely to be relevant?  The ideal might be the component that is most likely to be relevant and has the highest proportion of good things amongst its hits.

27. Running the search  How many titles and abstract can you check?  How easy will it be to decide to accept or reject a record?  Do something to “remember” the records you reject, unless you want to look at them again  Record the reason for rejection for “Excluded studies”, which might be those: For which you obtain full articles Which others might think should be in your review

28. Deciding where to search  Choose databases that are likely to provide a worthwhile yield  The components to focus on might vary between databases  Index terms may be different in different databases

29. Statistics of reviews: meta-analysis

30. Intervention 1 minute Count the number of flips or rolls and the number of deaths Heads is a death 1 is a death

31. Control 1 minute Count the number of flips or rolls and the number of deaths Tails is a death 6 is a death

33. Heterogeneity

35. Heterogeneity – planning for it Do you want heterogeneity in your review? Heterogeneity can occur throughout the review (i nterventions, participants, outcome measures and study designs) In your review, might heterogeneity lead to  Variation  Diversity  Complications  Messiness  Wide coverage  Ability to make comparisons  Contradictory findings? Which of these would you like to have in your review?

36. Heterogeneity – measuring and explaining it How sure are you about the factors that might drive heterogeneity in the results of the studies? The statistical tests measure heterogeneity in the results of the study, not in their content or conduct. Might statistical heterogeneity be due to more than one factor or due to a different factor than the one you are thinking of?

37. Dealing with heterogeneity Eligibility Descriptive Subgroup analyses Sensitivity analysis Separate meta-analyses

38. Subgroups

40. Subgroup analyses - planning Keep the number of subgroup analyses as low as possible, to reduce the possibility of false positive results Make sure that the ones you do are important Make sure you extract the relevant data Will you have enough power in a specific subgroup? Is it too uncommon or unlikely to have been studied? Will subgroups be reported by the original researchers, and in the way you need them? What will you do if they are not reported in the way you want? Do you have independent evidence for your predictions on what the subgroups will show (rather than evidence from the studies that would be included in the analysis)?

41. Subgroup analyses - interpretation The most statistically powerful estimate for an individual patient is likely to come from the full meta-analysis. But, this will not be meaningful if there is too much clinical heterogeneity in the meta-analysis. Will you do subgroup analyses to show that the results are similar for different people, or to identify people, settings or interventions where the results are different? Subgroup results might provide a more specific answer for an individual patient, but they suffer from being  Underpowered  More subject to the effects of chance

42. Extracting the data

43. What is the effect of needle length on local reaction to vaccination in babies?

44. Data extraction - why Reasons for doing data extraction:  Remembering the information  Organizing information into a particular structure  Summarising the content of the reports  Ensuring that you look for the key things  Making it easier to compare different studies  Making it easier to do meta-analyses and subgroup analyses  Assessing quality

45. Data extraction - how Data extraction form  Paper or electronic?  Picklists or freetext?  How much space do you need for each item?  Do you want to record what was planned in a study, what happened, or the difference (eg for the study’s eligibility criteria)? Think carefully about what you will use the data for. For example, do you want to know the mean age, the age range, the number of people in different age groups, or the results for different age groups separately? Or do you just want to know that an article has a particular type of age data? Do you need all the data? How much detail do you need?

46. Systematic reviewing  Formulating a clear question for the review  Stating objectives and eligibility criteria  Identifying (all) potentially eligible studies  Applying eligibility criteria  Assembling most complete dataset feasible  Analysing the dataset, using statistical synthesis and sensitivity analyses, if appropriate and possible  Preparing a structured report  Updating the review

47. Some addresses The Cochrane Collaboration www.cochrane.org The Cochrane Library www.TheCochraneLibrary.com m.clarke@qub.ac.uk