Week 3: Meta-analysis by hand

SKI3010 · Wed 17 Feb

ImportantQuiz 2 in this tutorial

Measures of frequency and association. Paper quiz, no devices. Prepare with the concept list and practice questions of last week.

Lecture

  • Introduction: meta-analysis
  • Meta-analysis by hand

Slides and materials

Lecture slides and other materials appear here before the lecture.

Tutorial

  • Quantitative data extraction

Hand in

  • A2a: Quantitative data extraction of all primary papers. Deadline Tue 23 Feb, 11:59 (pass/fail). How to submit
  • A2b: 2nd draft: introduction, methods, results. Deadline Tue 23 Feb, 11:59 (pass/fail). How to submit

Concepts and practice

These concepts are covered in Quiz 3 (next week’s tutorial, after carnival). Use the exercise “Meta-analysis by hand” from the tutorial as extra practice.

Concept list

Concept In one sentence
Effect size The measure of association that is pooled across studies, for example the OR, RR or a mean difference.
Log scale Ratios are pooled as ln(OR) or ln(RR) because their sampling distribution is symmetric on the log scale; results are transformed back with exp().
SE from a confidence interval SE = [ln(upper) − ln(lower)] / 3.92.
Inverse-variance weight Each study gets weight w = 1 / SE²: precise (usually larger) studies count more.
Pooled estimate The weighted average of the study effects: Σ(w × ln OR) / Σw, transformed back with exp().
SE of the pooled estimate 1 / √Σw.
Fixed-effect model Assumes all studies estimate one common true effect; differences are due to chance only.
Random-effects model Assumes the true effects differ between studies and estimates their average; adds the between-study variance τ² to each study’s variance.
Heterogeneity Variation in study results beyond what chance would explain.
Cochran’s Q Σ w × (ln OR − pooled ln OR)²; compared with its degrees of freedom (k − 1).
I² (Q − df) / Q × 100%: the share of the variation that is due to real differences between studies rather than chance (0% if Q < df).
τ² (tau-squared) The variance of the true effects between studies, used in the random-effects model.
Forest plot Graph of each study’s estimate and CI (box size = weight) with the pooled estimate as a diamond.

Practice questions

1. Three studies report: A, OR 1.20 (95% CI 0.80 to 1.80); B, OR 0.90 (0.70 to 1.16); C, OR 1.05 (0.85 to 1.30). Calculate ln(OR), SE and weight for each study.

Study ln(OR) SE w = 1/SE²
A 0.182 (0.588 + 0.223)/3.92 = 0.207 23.4
B −0.105 (0.148 + 0.357)/3.92 = 0.129 60.2
C 0.049 (0.262 + 0.163)/3.92 = 0.108 85.1

2. Calculate the fixed-effect pooled OR and its 95% CI.

Σw = 168.7; Σ(w × ln OR) = 4.26 − 6.35 + 4.15 = 2.07; pooled ln OR = 2.07/168.7 = 0.012, so OR = 1.01. SE = 1/√168.7 = 0.077; CI = exp(0.012 ± 1.96 × 0.077) = 0.87 to 1.18.

3. Q = 1.62 with 2 degrees of freedom. What is I², and what does that mean?

Q is smaller than df, so I² = 0%: the differences between the three studies are compatible with chance alone, and fixed- and random-effects models give the same result.

4. Which study has the largest weight, and why?

Study C (about 50% of the total weight): it has the narrowest CI, so the smallest SE and the largest inverse-variance weight.

Practice quiz

15 minutes, on paper, calculator allowed.

  1. Why are odds ratios pooled on the log scale? (1 point)
  2. A study reports OR 2.00 (95% CI 1.20 to 3.33). Calculate its SE and its weight. (2 points)
  3. Explain the difference between a fixed-effect and a random-effects model. (2 points)
  4. A meta-analysis reports I² = 83%. What does this mean, and what should the authors do next? (2 points)
  5. In a forest plot, what do the size of the box and the width of the diamond represent? (1 point)
  1. Ratios are skewed (0 to infinity, with 1 as null); on the log scale they are symmetric around 0 and approximately normally distributed.
  2. SE = [ln(3.33) − ln(1.20)] / 3.92 = (1.203 − 0.182)/3.92 = 0.260; w = 1/0.260² = 14.8.
  3. Fixed effect: one common true effect, differences are chance only. Random effects: true effects vary between studies; the model estimates their mean and gives relatively more weight to small studies.
  4. Most of the variation (83%) reflects real differences between studies. Use a random-effects model and explore the sources of heterogeneity (e.g. subgroups by design or population), and be careful with one pooled number.
  5. Box size: the weight of the study. Diamond width: the 95% CI of the pooled estimate.