Skip to main content Accessibility help

Empirical comparison of subgroup effects in conventional and individual patient data meta-analyses

  • Laura Koopman (a1), Geert J. M. G. van der Heijden (a1), Arno W. Hoes (a1), Diederick E. Grobbee (a1) and Maroeska M. Rovers (a1)...


Objectives: Individual patient data (IPD) meta-analyses have been proposed as a major improvement in meta-analytic methods to study subgroup effects. Subgroup effects of conventional and IPD meta-analyses using identical data have not been compared. Our objective is to compare such subgroup effects using the data of six trials (n = 1,643) on the effectiveness of antibiotics in children with acute otitis media (AOM).

Methods: Effects (relative risks, risk differences [RD], and their confidence intervals [CI]) of antibiotics in subgroups of children with AOM resulting from (i) conventional meta-analysis using summary statistics derived from published data (CMA), (ii) two-stage approach to IPD meta-analysis using summary statistics derived from IPD (IPDMA-2), and (iii) one-stage approach to IPD meta-analysis where IPD is pooled into a single data set (IPDMA-1) were compared.

Results: In the conventional meta-analysis, only two of the six studies were included, because only these reported on relevant subgroup effects. The conventional meta-analysis showed larger (age < 2 years) or smaller (age ≥ 2 years) subgroup effects and wider CIs than both IPD meta-analyses (age < 2 years: RDCMA -21 percent, RDIPDMA-1 -16 percent, RDIPDMA-2 -15 percent; age ≥2 years: RDCMA -5 percent, RDIPDMA-1 -11 percent, RDIPDMA-2 -11 percent). The most important reason for these discrepant results is that the two studies included in the conventional meta-analysis reported outcomes that were different both from each other and from the IPD meta-analyses.

Conclusions: This empirical example shows that conventional meta-analyses do not allow proper subgroup analyses, whereas IPD meta-analyses produce more accurate subgroup effects. We also found no differences between the one- and two-stage meta-analytic approaches.



Hide All
1. Appelman, CL, Claessen, JQ, Touw-Otten, FW, et al. Co-amoxiclav in recurrent acute otitis media: Placebo controlled study. BMJ. 1991;303:1450-1452.
2. Burke, P, Bain, J, Robinson, D, et al. Acute red ear in children: Controlled trial of non-antibiotic treatment in general practice. BMJ. 1991;303:558-562.
3. Clarke, MJ, Stewart, LA. Obtaining individual patient data from randomised controlled trials. In: Egger, M, Smith, GD, Altman, DG, eds. Systematic reviews in health care: Meta-analysis in context. London: BMJ Publishing Group; 2001:109-121.
4. Damoiseaux, RA, Van Balen, FA, Hoes, AW, et al. Primary care based randomized, double blind trial of amoxicillin versus placebo for acute otitis media in children aged under 2 years. BMJ. 2000;320:350-354.
5. Jeng, GT, Scott, JR, Burmeister, LF. A comparison of meta-analytic results using literature vs individual patient data; paternal cell immunization for recurrent miscarriage. JAMA. 1995;274:830-836.
6. Le Saux, N, Gaboury, I, Baird, M, et al. A randomized, double-blind, placebo-controlled noninferiority trial of amoxicillin for clinically diagnosed acute otitis media in children 6 months to 5 years of age. CMAJ. 2005;172:335-341.
7. Little, P, Gould, C, Williamson, I, et al. Pragmatic randomised controlled trial of two prescribing strategies for childhood acute otitis media. BMJ. 2001;322:336-342.
8. McCormick, DP, Chonmaitree, T, Pittman, C, et al. Nonsevere acute otitis media: A clinical trial comparing outcomes of watchful waiting versus immediate antibiotic treatment. Pediatrics. 2005;115:1455-1465.
9. Olkin, I, Sampson, A. Comparison of meta-analysis versus analysis of variance of individual patient data. Biometrics. 1998;54:317-322.
10. Rovers, MM, Glasziou, P, Appelman, CL, et al. Antibiotics for acute otitis media: A meta-analysis with individual patient data. Lancet. 2006;368:1429-1435.
11. Simmonds, MC, Higgins, JP, Stewart, LA, et al. Meta-analysis of individual patient data from randomized trials: A review of methods used in practice. Clin Trials. 2005;2:209-217.
12. Smith, CT, Williamson, PR, Marson, AG. An overview of methods and empirical comparison of aggregate data and individual patient data results for investigating heterogeneity in meta-analysis of time-to-event outcomes. J Eval Clin Pract. 2005;11:468-478.
13. Steinberg, KK, Smith, SJ, Stroup, DF, et al. Comparison of effect estimates from a meta-analysis of summary data from published studies and from a meta-analysis using individual patient data for ovarian cancer studies. Am J Epidemiol. 1997;145:917-925.
14. Stewart, LA, Parmar, MK. Meta-analysis of the literature or of individual data: Is there a difference? Lancet. 1993;341:418-422.
15. Stewart, LA, Tierney, JF. To IPD or not to IPD? Advantages and disadvantages of systematic reviews using individual patient data. Eval Health Prof. 2002;25:76-97.



Full text views

Total number of HTML views: 0
Total number of PDF views: 0 *
Loading metrics...

Abstract views

Total abstract views: 0 *
Loading metrics...

* Views captured on Cambridge Core between <date>. This data will be updated every 24 hours.

Usage data cannot currently be displayed