Mega-trials vs. meta-analysis: precision vs. heterogeneity? - PubMed

Mega-trials vs. meta-analysis: precision vs. heterogeneity?

Ian Shrier et al. Contemp Clin Trials. 2007 May.

Abstract

In recent years, several authors have suggested there is a need for more very large or "mega-trials" (defined in this manuscript as a trial powered to address subgroup differences/interactions/secondary analyses) to answer important clinical questions. Because mega-trials are expensive and funding for clinical research is limited, increasing the number of mega-trials limits funding for other research. The advantages of this approach compared with funding more focused RCTs needs to be debated. Because there is no method to determine gold standard for which method gives the correct answer, we provide theoretical arguments that demonstrate that the two approaches are similar with respect to sample size requirements and the mega-trial approach provides a small advantage with respect to minimizing confounding by chance. However, the inherent heterogeneity in a series of smaller trials may represent a significant advantage over a single mega-trial.

Similar articles

• Practical and updated guidelines on performing meta-analyses of non-randomized studies in interventional cardiology.

  Navarese EP, Koziński M, Pafundi T, Andreotti F, Buffon A, Servi SD, Kubica J. Navarese EP, et al. Cardiol J. 2011;18(1):3-7. Cardiol J. 2011. PMID: 21305479 Review.

• [Meta-analysis as a tool for gaining knowledge].

  Koch A, Ziegler S. Koch A, et al. Med Klin (Munich). 2000 May;95(1 Spec No):83-90. Med Klin (Munich). 2000. PMID: 10851854 Review. German.

• A graphical method for exploring heterogeneity in meta-analyses: application to a meta-analysis of 65 trials.

  Baujat B, Mahé C, Pignon JP, Hill C. Baujat B, et al. Stat Med. 2002 Sep 30;21(18):2641-52. doi: 10.1002/sim.1221. Stat Med. 2002. PMID: 12228882

• Can trial sequential monitoring boundaries reduce spurious inferences from meta-analyses?

  Thorlund K, Devereaux PJ, Wetterslev J, Guyatt G, Ioannidis JP, Thabane L, Gluud LL, Als-Nielsen B, Gluud C. Thorlund K, et al. Int J Epidemiol. 2009 Feb;38(1):276-86. doi: 10.1093/ije/dyn179. Epub 2008 Sep 29. Int J Epidemiol. 2009. PMID: 18824467

Cited by

• Virtual Rehabilitation of the Paretic Hand and Arm in Persons With Stroke: Translation From Laboratory to Rehabilitation Centers and the Patient's Home.

  Fluet G, Qiu Q, Patel J, Mont A, Cronce A, Yarossi M, Merians A, Adamovich S. Fluet G, et al. Front Neurol. 2021 Jan 28;12:623261. doi: 10.3389/fneur.2021.623261. eCollection 2021. Front Neurol. 2021. PMID: 33584529 Free PMC article.

• Updating the evidence for the role of corticosteroids in severe sepsis and septic shock: a Bayesian meta-analytic perspective.

  Moran JL, Graham PL, Rockliff S, Bersten AD. Moran JL, et al. Crit Care. 2010;14(4):R134. doi: 10.1186/cc9182. Epub 2010 Jul 13. Crit Care. 2010. PMID: 20626892 Free PMC article. Review.

• A mega-analysis of expression quantitative trait loci (eQTL) provides insight into the regulatory architecture of gene expression variation in liver.

  Strunz T, Grassmann F, Gayán J, Nahkuri S, Souza-Costa D, Maugeais C, Fauser S, Nogoceke E, Weber BHF. Strunz T, et al. Sci Rep. 2018 Apr 12;8(1):5865. doi: 10.1038/s41598-018-24219-z. Sci Rep. 2018. PMID: 29650998 Free PMC article.

• Return to work following shoulder arthroplasty: A systematic review.

  Lalehzarian SP, Agarwalla A, Liu JN. Lalehzarian SP, et al. World J Orthop. 2022 Sep 18;13(9):837-852. doi: 10.5312/wjo.v13.i9.837. eCollection 2022 Sep 18. World J Orthop. 2022. PMID: 36189336 Free PMC article.

• The importance of small samples in medical research.

  Indrayan A, Mishra A. Indrayan A, et al. J Postgrad Med. 2021 Oct-Dec;67(4):219-223. doi: 10.4103/jpgm.JPGM_230_21. J Postgrad Med. 2021. PMID: 34845889 Free PMC article.

MeSH terms

LinkOut - more resources

• Full Text Sources

  • ClinicalKey
  • Elsevier Science

• Medical

  • MedlinePlus Health Information