1. An Introduction to Critical Appraisal Laura Wilkes Trust Librarian West Suffolk Foundation Trust Laura.Wilkes@wsh.nhs.uk Last updated May 2012
2. Learning Outcomes By the end of this session you will: o Understand what Critical Appraisal is o Be aware of some of the different types of research o Be able to interpret basic statistics within a research paper o Gain experience in critically appraising a research paper
3. Evidence Based Practice “"Evidence-based medicine is the conscientious, explicit and judicious use of current best evidence in making decisions about the care of individual patients.” Sackett, 1996
4. Hierarchy of Evidence
5. Types of Research Systematic Reviews A literature review focused on a single question which tries to identify, appraise, select and synthesize all high quality research relevant to that question. Combines results of several RCTs or other types of evidence Systematic reviews follow a clear sequence of steps: Defining an appropriate question Searching the literature – published and unpublished, English & non- English Assessing the studies – involves 2 independent reviewers Combining the results & producing a “bottom-line” Placing the findings into context Advantages Limits bias Good quality evidence Added power by synthesising individual study results
6. Types of Research Experimental: Randomised Controlled Trials (RCTs) Randomly assign individuals to an intervention group or a control group in order to measure the effectiveness of an intervention. Gold standard for treatment evaluations However, some studies are not suitable for RCTs
7. Types of Research Observational Studies Cohort Studies A non-experimental study design Follows a group of people (a cohort), and then looks at how events differ among people within the group. Follow up period can be years or decades Prospective cohort studies (which track participants forward in time) are more reliable than retrospective cohort studies Can be expensive to conduct
8. Types of Research Observational Case-Control Study Examines a group of people who have experienced an event (usually an adverse event) and a group of people who have not experienced the same event, and looks at what risk factors both groups have been exposed to Retrospective, therefore prone to recall bias, but quick & involve small numbers Primary method of studying new or unusual outcomes Case-Series Analysis of series of people with the disease there is no comparison group
9. Critical Appraisal The process of systematically weighing up the quality and relevance of research to see how useful it is in decision making It is the balanced assessment of benefits and strengths of research against its flaws and weaknesses Increases the effectiveness of your reading It can help you make informed decisions Is a skill that needs to be practised
10. How do I Appraise?• You don’t need to be a statistics expert• Ready-made checklists help you focus on the most important aspects of the article Different checklists available for different types of research (RCTs, systematic reviews, case-control studies, etc). Checklist for Qualitative research Available free from CASPhttp://www.casp-uk.net
11. Critical Appraisal Critical appraisal of any study design must assess:Validity Were sound scientific methods used? Chance / Bias / Confounding Factors Results What are the results and how are they expressed? Relevance Are the findings generalisable – can they be applied to settings / situations outside the research study? Do these results apply to my local context?
12. Potential Errors of Research Chance A random error appearing to cause an association between an intervention and an outcome. Probability of a random error is estimated using statistics (p values & confidence intervals) Bias The deviation of results from the truth due to systematic error in the research methodology Selection bias – when two groups being studied differ systematically in some way Observer bias – where there are systematic differences in the way groups are treated or in how information is collected Confounding Factors An error of interpretation Where part of the observed relationship between two variables is due to the action of a third variable Known confounders: e.g. age, gender, smoking, etc.
13. Critical Appraisal of an RCT Screening questions: 1. Did the study ask a clearly focused research question? Patient / Intervention / Outcome Is it relevant to you? 2. Did the authors use an appropriate research method? Is an RCT the most appropriate? If the answer to these questions is “YES” you can carry on with the rest of the checklist!
14. RCT Appraisal Checklist continued Detailed Questions: 3. Were participants appropriately allocated to groups? Sample: Is it representative of the target population (the population to which the results will be applied) Convenience sampling? Exclusion / Inclusion criteria – do you agree? If too selective results may not be generalisable Bias? Are the groups balanced? Important that groups are similar at the beginning of a trial so there is more chance of differences at the end being due to the intervention Look at the Baseline Characteristics Table Was group allocation truly random? Bias can occur if patients, carers, or researchers can influence allocation
15. Randomisation Randomisation ensures individuals have an equal chance of being allocated to any Group Potential confounding factors will be equally distributed between groups Successful randomisation requires that group allocation cannot be predicted in advance – allocation concealment avoids bias Allocation concealment ensures all those involved in the trial are unable to predict the allocation of the next participant until that participant is enrolled. Methods include telephone randomisation, or using consecutive sealed opaque envelopes. A good study should indicate who generated the randomisation sequence, the method used, and how concealment was achieved & monitored
17. Permuted Block Randomisation Used for small studies to maintain reasonably good balance among groupsWith a block size of 4 for two groups (A,B), there are 6 possible permutations and they can be coded as:1=AABB, 2=ABAB, 3=ABBA, 4=BAAB, 5=BABA, 6=BBAAEach number in the random number sequence in turn selects the next block, determining the next four participant allocations (ignoring numbers 0,7,8 and 9).e.g., The sequence 67126814…. will produce BBAA AABB ABAB BBAA AABB BAAB.
18. Stratified Block Randomisation A set of permuted blocks is generated for each combination of prognostic factors E.g. age group, severity of condition, and treatment centre. Stratification means having separate block randomisation schemes for each combination of characteristics („stratum‟) For example, in a study where you expect treatment effect to differ with age and sex you may have four strata: male over 65, male under 65, female over 65 and female under 65
19. Questions continued 4. Were participants, staff and study personnel “blind” to participants study group? Withholding information about the assigned interventions from people involved in the trial who may be influenced by this knowledge Eliminates error through bias Is blinding always possible? Different levels of Blinding Single- blind Trial Either the researcher or the subject is blind to the allocation Double-blind Trial Both researcher and subject are blinded Triple-blind Trial Subject, researcher and analyst
20. 5. Were all the participants who entered the trial accounted for at its conclusion? Loss to follow up? A common cause of missing data, especially in long-term studies How important are the losses? 5% probably OK but >20% poses threat to validity Losses equally distributed? Intention to treat analysis? Analysing people at the end of the trial, in the groups to which they were randomised, even if they did not receive the intended intervention Maintains randomisation Prevents bias caused by loss of participants 6. Were all the participants in all groups followed up and data collected the same way? Were groups treated equally? Followed over the same time period / received same attention Bias? Differences in the way data collected, measurements taken etc. if individuals know which group they have been allocated to
21. 7. Did the study have enough participants to minimise the play of chance? Before calculating the sample size, a clinically significant treatment effect is estimated POWER Calculation: calculates how large the sample should be in order to have a high chance of detecting a true difference between the groups. Avoids a type I (false positive) or type II (false negative) error Calculated before the study begins Look for 80% - 90% power –probability of finding a significant difference with a given sample size Sample size increases when a small treatment effect is expected & with higher power.
22. Are the Results Significant? 8. How are the results presented and what is the main result? What sort of data have they got & have they used appropriate statistical tests? Are the results expressed in terms of likely harm or benefit? Relative Risk Numbers Needed to Treat How meaningful is the result?
23. Event RatesNumber of people experiencing an event as a proportion of the number of people in the population• Form the basis of other calculations Control Event Rate (CER) Experimental Event Rate (EER)Emerg Med J 2008 25: 26-29:Proportion with recurrent headache (whole sample) CER = 12/31 = 39% EER = 8/30 = 27%
24. Risk of benefit and harm Relative Risk (RR) = compares the risk in 2 different groups of people tells us how many times more likely it is that an event will occur in the treatment group relative to the control group EER / CER Relative Risk of 1 means the risk is the same in each group <1 = treatment reduces risk of event >1 = treatment increases risk of event 27/39 = 0.69 = treatment reduces risk of event Risk of headache is 0.69 times lower in the treatment group than in the control group.
25. Risk continued Absolute risk reduction (ARR) Difference in risk between experimental and control groups Risk of Event in Control Group – Risk of Event in intervention group ARR=0 Treatment has no effect ARR positive – Treatment is beneficial ARR negative – Treatment is harmful 39% - 27% = 12% Dexamethasone reduces the absolute risk of recurrent headache by 12%
26. Relative Risk Reduction (RRR) tells us the reduction in the rate of the outcome in the treatment group relative to that in the control group ARR / CER Or 1 – RR 0.12 / 0.39 = 0.31 = 31% 1-0.69 = 0.31 = 31% Dexamethasone reduces the risk of recurrent headache by 31% relative to that occurring in the control group.
27. Absolute Risk Reduction & RelativeRisk Reduction Results of hypothetical trial of a new drug for myocardial infarction
28. Compare with Low Risk Patients Later studied in a lower risk population: 10% mortality rate at 30 days among untreated 7.5% mortality among treated Absolute Risk Reduction is therefore 2.5% 10% - 7.5% = 2.5% Relative Risk Reduction is 25% 2.5 / 10 = 0.25 = 25% Relative Risk Reduction is often more impressive than Absolute Risk Reduction The lower the event rate the smaller the absolute risk reduction
29. Odds Ratio Odds = number of Headache headache No events / number of non Odds events Odds Ratio = odds in treatment group / odds in control group Treatment 8/31 8 23 0.35 If odds is greater than 1 then the event (outcome) is more likely Placebo 12/3 12 20 0.6 to happen than not. 2 Odds Ratio = 35/60 = 0.59 Odds of recurrent headache almost 50% less in the treatment group
30. Numbers Needed to Treat Measures the impact of a treatment or intervention States how many patients need to be treated in order to prevent an event which would otherwise occur. NNT = 10 means that 10 patients need to be treated to prevent one adverse outcome The closer to 1 the better Calculation: 1 / ARR (if ARR expressed as a proportion) 100/ARR (if ARR expressed as a %) 100/12 = 8
31. Results 9. How precise are the results? P Values P=Probability A p-value is a measure of statistical significance which tells us the probability of an event occurring due to chance alone P values only from 0 to 1 If P Value is very small (e.g. P<0.001) the result is unlikely to be due to chance (1 in 1000) Generally, look for P<0.05 (1 in 20)
32. P - valuesIn simple terms, probability (p-value) can only take values between 0 and 1:0|-----------------------|--------------------|1Impossible…....... Absolutely certain…If p=0.001 the likelihood of a result happening by chance is extremely low: 1 in 1000If p=0.05 it is fairly unlikely that the result happened by chance 1 in 20If p=0.5 it is fairly likely that the result happened by chance 1 in 2If p=0.75 it is very likely that the result happened by chance 3 in 4
33. Confidence Intervals An alternative way of assessing the effects of chance The result of the trial is a “point estimate” – if you ran the trial again you will get a different result The Confidence Interval gives the range in which you think the real answer The 95% CI is the range in which we are 95% certain that the true population value lies Look at how wide the interval is, and the values at each end E.g. RR = 0.69 95% CI 0.33 to 1.45
34. Forest Plot – Simple Example The shorter the Line of No Effect Confidence Interval (CI) Individual sample the more confident we size can be that the results Combined Results are true Best Estimate If the CI crosses the line of no effect, then theConfidence Interval results of that study are not statistically significant Line of No Effect = 1 for Relative Risk or Odds Ratio Favours Treatment Favours Control 0 for Mean results
35. Relevance 10. Were all important outcomes considered so the results can be applied? Does your local setting / population differ from that in the research in ways that would produce different results? Can you provide the same treatment in your local setting? Does any benefit reported outweigh any harm? Should policy or practice change as a result of this research?
36. Is there a Systematic Review on the subject? …… Check the Cochrane LibraryNo Cochrane Reviews, but 2 “Other Reviews” – SystematicReviews but not produced by the Cochrane Collaboration.
37. Conclusion Critical Appraisal is part of Evidence Based Healthcare It takes practice Use CASP checklists Depth of Appraisal is your choice Only you can assess usefulness
38. Useful websites www.healthknowledge.org.uk/interactive- learning/finding-and-appraising-the-evidence www.thennt.com/ www.casp-uk.net/ www.wikipedia.org very good for a basic guide to statistics in critical appraisal. Search for critical appraisal.