Designing Clinical Research and Interpreting Clinical Evidence

1. Designing Clinical Research and Interpreting Clinical Evidence Advances in Maternal and Neonatal Health Everyone must be a skeptic about clinical information. I can tell you what information was used by the panel convened by WHO, but you should decide for yourself. Everyone must be a skeptic about clinical information. I can tell you what information was used by the panel convened by WHO, but you should decide for yourself.

2. 2 Designing Clinical Research and Interpreting Clinical Evidence Objective of Using Clinical Evidence To promote care based on best available evidence To encourage practitioners to develop their skills in obtaining, evaluating and incorporating evidence into daily clinical practice In order to achieve that, practitioners should understand and intellectually evaluate new clinical data as it becomes available Individually skeptical to change this workshop. All studies are cited on the page. Individually skeptical to change this workshop. All studies are cited on the page.

3. 3 Designing Clinical Research and Interpreting Clinical Evidence In an Ideal World The most effective care for every condition would be known Every clinician would know the most effective care for every patient Every clinician would practice the most effective care that she/he knows Capacity and capabilityCapacity and capability

4. 4 Designing Clinical Research and Interpreting Clinical Evidence In the Real World Much of what should be known is not known Much that is known, is not known by most clinicians Clinicians often fail to practice what they know to be the most effective form of care Research has gaps, some of the evidence is lacking. Information is not available Things get in the way of us practicing the best wayResearch has gaps, some of the evidence is lacking. Information is not available Things get in the way of us practicing the best way

5. 5 Designing Clinical Research and Interpreting Clinical Evidence Evidence-based medicine is the systematic, scientific and explicit use of current best evidence in making decisions about the care of individual patients.

6. 6 Designing Clinical Research and Interpreting Clinical Evidence Levels of Evidence and Grades of Recommendations 1a: Reviewers search for all randomized controlled trials on a subject, review the quality of the studies, and combine results that are of the best quality available and give a pooled result and recommendations for practice and for further research. Systematic reviews of RCTs are in Cochrane Library. 1b: Individual RCT compares two randomly assigned groups with similar characteristics. One group gets the intervention being studied and the other gets a placebo or whatever the routine treatment is. Outcomes are evaluated to see which treatment is better. 2a: A cohort study studies a group of people over time to see if their characteristics are associated with the development of certain outcomes. In a review, several cohort studies on the same subject are evaluated for their quality, results are pooled and a general recommendation is made. 2b: Individual cohort study- results from only one researcher whose group is followed over time 3a: A case-control study compares two similar groups, one with and one without a disease, and looks in their pasts to see if certain risk factors were present. A review compiles the results of several studies and makes conclusions. 3b: Individual case-control study compares two groups (one with and one without disease to see about previous risk factors. 4: Case series describes all the patients with a specific problem. 5: A person gives her/his opinion for practice, without having evidence to support it.1a: Reviewers search for all randomized controlled trials on a subject, review the quality of the studies, and combine results that are of the best quality available and give a pooled result and recommendations for practice and for further research. Systematic reviews of RCTs are in Cochrane Library. 1b: Individual RCT compares two randomly assigned groups with similar characteristics. One group gets the intervention being studied and the other gets a placebo or whatever the routine treatment is. Outcomes are evaluated to see which treatment is better. 2a: A cohort study studies a group of people over time to see if their characteristics are associated with the development of certain outcomes. In a review, several cohort studies on the same subject are evaluated for their quality, results are pooled and a general recommendation is made. 2b: Individual cohort study- results from only one researcher whose group is followed over time 3a: A case-control study compares two similar groups, one with and one without a disease, and looks in their pasts to see if certain risk factors were present. A review compiles the results of several studies and makes conclusions. 3b: Individual case-control study compares two groups (one with and one without disease to see about previous risk factors. 4: Case series describes all the patients with a specific problem. 5: A person gives her/his opinion for practice, without having evidence to support it.

7. 7 Designing Clinical Research and Interpreting Clinical Evidence Conducting Research: Steps Formulate research question Design study Choose subjects Choose variables to be measured Collect data Analyze data Draw conclusions

8. 8 Designing Clinical Research and Interpreting Clinical Evidence Definitions Quality of test Sensitivity: Likelihood that diagnostic test will indicate presence of disease when disease is actually present (true positive rate) Specificity: Likelihood that diagnostic test will indicate absence of disease when disease is actually absent Usefulness of result Positive predictive value: Likelihood that positive test result actually means that disease is present Negative predictive value: Likelihood that negative test result actually mean that disease is absent The quality of a test is the ability of the test to say the disease is there or not there. The usefulness of a result if the ability of a person to believe a positive or negative test result. Sensitivity = (a/a+c), the likelihood that if someone has HIV that the blood test will be positive. Specificity = (d/b+d), the likelihood that if someone does not have HIV that the blood test will be negative PPV = (a/a+b), likelihood that if someone�s HIV test is positive that they have HIV NPV = (d/c+d), the likelihood that if someone�s HIV test is negative that they really do not have HIV No test is 100% sensitive of specific.The quality of a test is the ability of the test to say the disease is there or not there. The usefulness of a result if the ability of a person to believe a positive or negative test result. Sensitivity = (a/a+c), the likelihood that if someone has HIV that the blood test will be positive. Specificity = (d/b+d), the likelihood that if someone does not have HIV that the blood test will be negative PPV = (a/a+b), likelihood that if someone�s HIV test is positive that they have HIV NPV = (d/c+d), the likelihood that if someone�s HIV test is negative that they really do not have HIV No test is 100% sensitive of specific.

9. 9 Designing Clinical Research and Interpreting Clinical Evidence Prototype 2 X 2 Table

10. 10 Designing Clinical Research and Interpreting Clinical Evidence 2 X 2 Table (continued)

11. 11 Designing Clinical Research and Interpreting Clinical Evidence Meta Analysis Is one tool that may allow useful information to be obtained from multiple studies Is systematic evaluation of collection of several studies which are similar in design, study populations and outcomes examined Combines data appropriately to find answer to important question in cumulative information in literature Is systematic review of medical literature Increases the power of a group of studies by pooling results.Increases the power of a group of studies by pooling results.

12. 12 Designing Clinical Research and Interpreting Clinical Evidence Measures of Statistical Significance: Relative Risk Rate of risk of outcome in exposed individuals to risk in unexposed individuals From cohort study only Reflects risk to total population Relative risk 1: No difference in outcome between 2 groups < 1: Less risk of outcome > 1: Higher risk of outcome The important point to learn is that if there is no difference in the outcome between the two groups, the RR (or OR) = 1 (ratio of 1:1 = 1). It is equally likely to happen in both groups. If the outcome is less likely to happen in one group, the RR (or OR) for them is <1.The important point to learn is that if there is no difference in the outcome between the two groups, the RR (or OR) = 1 (ratio of 1:1 = 1). It is equally likely to happen in both groups. If the outcome is less likely to happen in one group, the RR (or OR) for them is <1.

13. 13 Designing Clinical Research and Interpreting Clinical Evidence Measures of Statistical Significance: Odds Ratio Compares likelihood of outcome being studied occurring in group receiving intervention (experimental) with group not receiving (control) From case control Does not reflect total population, but can closely estimate relative risk Graphically represented on logarithmic scale Vertical line at 1: No difference in outcome between two groups Ratios less than 1 (left of vertical line): Improvement of outcome Ratios more than 1: Worse outcome

14. 14 Designing Clinical Research and Interpreting Clinical Evidence Measures of Statistical Significance: 95% Confidence Interval Confidence interval: Range in which true effect size can be found 95% chance that true effect size lies within 95% confidence interval If confidence interval overlaps 1.0, then there is a > 5% possibility that observed outcome difference is due to chance Very wide � results less believable Very narrow � more believable All RR or OR are not exactly correct, but have range within which they can fall. The range is the confidence interval. It describes how accurate and believable the results are. If the confidence interval overlaps one, the result may simply be due to chance. If the interval range is very wide, the results are less likely to be accurate or meaningful.All RR or OR are not exactly correct, but have range within which they can fall. The range is the confidence interval. It describes how accurate and believable the results are. If the confidence interval overlaps one, the result may simply be due to chance. If the interval range is very wide, the results are less likely to be accurate or meaningful.

15. 15 Designing Clinical Research and Interpreting Clinical Evidence

16. 16 Designing Clinical Research and Interpreting Clinical Evidence Measures of Statistical Significance: p Value The probability, under a null hypothesis, of data as extreme or more extreme than was observed in one study Conventionally set as 0.05 Equivalent to 5% Difference is significant if p value is less than 0.05 (< 0.05) Means that there is less than a 5% chance that the result obtained is due to chance, or 95% certain that result obtained by the intervention is true

17. 17 Designing Clinical Research and Interpreting Clinical Evidence Statistical Significance vs. Clinical Significance It is up to the practitioner to decide whether a statistically significant or non-significant result is clinically significant It is important to note that results can be statistically significant, but may not be clinically significant (and may not be meaningful or warrant a change in practice.)It is important to note that results can be statistically significant, but may not be clinically significant (and may not be meaningful or warrant a change in practice.)

18. 18 Designing Clinical Research and Interpreting Clinical Evidence Summary Evidence-based medicine should be used to set a standard of care New data should be evaluated critically to determine whether to change standards

19. 19 Designing Clinical Research and Interpreting Clinical Evidence References Hulley SB and SR Cummings. 1988. Designing Clinical Research: An epidemiological approach. Williams and Wilkins: Baltimore, Maryland.