Nazir Ibrahim MD,MRCP

​

Associate professor

Cochrane collaboration

​

• The very nature of science is to pose questions and seek answers.

Hoped-for Renaissance! What does it take?

courses

Key topics in EBM

Evidence pyramid

McGovern D, Summerskill W, Valori R, Levi M..

Problem

��

• Many RCTs do not produce statistically significant results.

​

• Significant result could not be demonstrated because of� an insufficient sample size (i.e., an insufficient number of enrolled patients).

​

?

• a drug that reduces mortality by 10% mortality from myocardial infarction may need a study �� including 10.000 patients

9

“Mega-study”

Single large studies are liable to:

​

• Type I error (false positive result)
• Type II error (false negative result):
• occur in 20% of research
• Generalizability of results can be questioned.

10

Magic solution

​

• In a meta-analysis, the results from all RCTs are combined to�produce a summary result using a statistical technique.

​

• By combining the results from all RCTs, a large number of patients are examined and a sufficient sample size is achieved

​

systematic review/+-MA

Last Step of meta-analysis

(forest plot)

​

Reporting the results

Forest plots: trying to see the wood and the trees

​

• It is the graphical / visual representation of Meta analysis

The origin of forest plots goes back to the 1970s. Freiman

The plot allows readers to see the information from the individual studies that went into the meta-analysis at a glance

• v

For dichotomous data ,the three main options are the �odds ratio (OR), the risk ratio (RR) , the risk difference (RD).

A fixed-effect meta-analysis (also known as common-effect meta-analysis) assumes that the intervention effect is the same in every trial. A random-effects meta-analysis

Practical guide

The vertical line is the line of no effect (i.e. the position at which there is no clear difference between the intervention group and the control group).

Intervention & control n/N

Relative risk

Studies IDs

Weight

More information

• The weight (in %) indicates the influence an individual study has had on the pooled result.
• In general, the bigger the sample size and the narrower the confidence interval (CI), the higher the percentage weight,

​

• the larger the box, and more the influence the study has on the pooled result.

​

The p-value indicates the level of statistical significance. If the diamond shape does not touch the line of no effect, the difference found between the two groups was statistically significant. In that case, the p-value is usually < 0.05.

• The horizontal lines through the boxes illustrate the length of the confidence interval.

​

• The longer the lines, the wider the confidential interval, the less reliable the study results.

​

• The width of the diamond serves the same purpose

Significance of Meta-analysis: Example

Mitchell JRA. Timolol after myocardial infarction: an answer or a new set of questions? BMJ 1981;282:1565-70:

​

"despite claims that they reduce arrhythmias, cardiac work, and infarct size, we still have no clear evidence that ß blockers improve long-term survival after infarction despite almost 20 years of clinical trials."

​

36

Cumulative meta analysis

Cumulative Meta-analysis: Example

41

Cumulative meta analysis

Network meta-analysis

• Health care practitioners, decision-makers, and consumers want to know which treatment is preferable among many competing options

​

• Network meta-analysis is an extension of meta-analysis that allows the simultaneous comparison of multiple interventions.

46

Network Meta-Analysis