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Impact of single centre status on estimates of intervention effects in trials with continuous outcomes: meta-epidemiological study

BMJ 2012; 344 doi: (Published 14 February 2012) Cite this as: BMJ 2012;344:e813

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  1. Aïda Bafeta, PhD student1,
  2. Agnes Dechartres, assistant professor of epidemiology123,
  3. Ludovic Trinquart, senior statistician4,
  4. Amélie Yavchitz, PhD student1,
  5. Isabelle Boutron, associate professor of epidemiology1233,
  6. Philippe Ravaud, professor of epidemiology and director1234
  1. 1INSERM U738, Paris, France
  2. 2Assistance Publique-Hôpitaux de Paris, Centre d’Epidémiologie Clinique, Hôpital Hôtel-Dieu
  3. 3Université Paris Descartes—Sorbonne Paris Cité, Paris, France
  4. 4French Cochrane Centre, Paris, France
  1. Correspondence to: A Dechartres Centre d’Epidémiologie Clinique, Hôpital Hôtel-Dieu, 1 place du Parvis Notre Dame, 75004 Paris, France agnes.dechartres{at}
  • Accepted 24 November 2011


Objective To compare estimates of intervention effects between single centre and multicentre randomised controlled trials with continuous outcomes.

Design Meta-epidemiological study.

Data sources 26 meta-analyses totalling 292 randomised controlled trials (177 single centre, 115 multicentre) with continuous outcomes published between January 2007 and January 2010 in the Cochrane database of systematic reviews.

Data extraction Data were extracted on characteristics of trials, single or multicentre status, risk of bias using the risk of bias tool of the Cochrane Collaboration, and results.

Data synthesis The intervention effects were estimated with standardised mean differences. For each meta-analysis, random effects meta-regression was used to estimate the difference in standardised mean differences between single centre and multicentre trials. Differences in standardised mean differences were then pooled across meta-analyses by a random-effects meta-analysis model. A combined difference in standardised mean differences of less than 0 indicated that single centre trials showed larger treatment effects, on average, than did multicentre trials. Because single centre trials may be more prone to publication bias and may have lower methodological quality than multicentre trials, sensitivity analyses were done with adjustment for sample size and domains of the risk of bias tool.

Results Single centre trials showed larger intervention effects than did multicentre trials (combined difference in standardised mean differences −0.09, 95% confidence interval −0.17 to −0.01, P=0.04), with low heterogeneity across individual meta-analyses (I2=0%, between meta-analyses variance τ2=0.00). Adjustment for sample size slightly attenuated the difference (−0.08, −0.17 to 0.01). Adjustment for risk of bias yielded similar estimates with wider confidence intervals, some of them crossing 0 (−0.09, −0.17 to 0.00 for overall risk of bias).

Conclusions On average, single centre clinical trials with continuous outcomes showed slightly larger intervention effects than did multicentre trials. Further research is needed to investigate potential causes of these differences.


  • We thank Mickael Randrianandrasana, Gabriel Baron, Elodie Perrodeau, and Ali Alkhafaji for data extraction of study results in the individual reports of trials.

  • Contributors: AB searched and selected the trials, extracted and analysed the data, interpreted the results, and drafted the manuscript. AD conceived the study, selected the trials, extracted and analysed the data, interpreted the results, and drafted the manuscript. She is the guarantor. LT conceived the study, analysed the data, interpreted the results, and drafted the manuscript. AY extracted the data and interpreted the results. IB and PR conceived the study, interpreted the results, and drafted the manuscript. All authors, external and internal, had full access to all of the data (including statistical reports and tables) in the study and can take responsibility for the integrity of the data and the accuracy of the data analysis.

  • Funding: This study received no specific funding.

  • Competing interests: All authors have completed the ICMJE uniform disclosure form at (available on request from the corresponding author) and declare: no support from any organisation for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; and no other relationships or activities that could appear to have influenced the submitted work.

  • Ethical approval: Not required.

  • Data sharing: No additional data available.

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