The DOI matches its Crossref record; 72 of the 72 references it cites were found in a registry or an index.
Single-Center Trials Show Larger Treatment Effects Than Multicenter Trials: Evidence From a Meta-epidemiologic Study
Abstract
BACKGROUND: A recent study suggested that results of single-center trials are frequently contradicted when similar trials are performed in multicenter settings. PURPOSE: To perform a meta-epidemiologic study to evaluate whether estimates of treatment effect differ between single-center and multicenter randomized, controlled trials (RCTs). DATA SOURCES: MEDLINE was searched via PubMed for meta-analyses of RCTs with binary outcomes that were published between August 2008 and January 2009 and in the first 6 months of 2010 in the 10 leading journals of each medical specialty. One issue of the Cochrane Database of Systematic Reviews was also searched. STUDY SELECTION: All individual RCTs included in the meta-analyses were selected. DATA EXTRACTION: Data were extracted and their quality was assessed by use of the risk of bias tool of the Cochrane Collaboration. DATA SYNTHESIS: The primary outcome was the ratio of odds ratios (ROR), used to quantify the difference in estimated intervention effect between single-center and multicenter RCTs. An ROR less than 1 would indicate larger estimates of the intervention effect in single-center trials. Sensitivity analyses were performed with adjustment for sample size, risk of bias within RCTs, and variance of the log odds ratio to take publication bias into account. Forty-eight meta-analyses were selected, including 421 RCTs (223 were single-center and 198 were multicenter). Single-center RCTs showed a larger intervention effect than did multicenter RCTs (combined ROR, 0.73 [95% CI, 0.64 to 0.83]), with low heterogeneity across individual meta-analyses (I(2) = 12.0%; P = 0.24). Adjustment for sample size yielded consistent results (ROR, 0.85 [CI, 0.74 to 0.97]), as did adjustment for risk of bias within RCTs, such as allocation concealment (ROR, 0.76 [CI, 0.67 to 0.86]), and variance of log odds ratio (ROR, 0.83 [CI, 0.72 to 0.96]). LIMITATION: Despite sensitivity analyses, meta-confounding cannot be fully excluded. CONCLUSION: Single-center RCTs showed larger treatment effects than did multicenter RCTs, a finding that was consistent in all sensitivity analyses. These results suggest that this item should be considered when the results of RCTs and meta-analyses are interpreted. PRIMARY FUNDING SOURCE: Academic grant Recherche sur la Recherche from the Délégation Interrégionale à la Recherche Clinique (DIRC), Ile de France, Assistance Publique-Hôpitaux de Paris (APHP).
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“Although most included studies were conducted at a single center, which may result in a more significant treatment effect and risk of bias 28 , we identified many cross-country collaborations.”
From Global mapping of randomized controlled trials in dentistry (2024) · cites this paper as [28]
Citations
Cites
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“The amount of the difference was substantial, with a relative increase of 27% in the intervention effect estimate for single-center RCTs as compared with multicenter RCTs; this result is similar to the bias induced by unclear or inadequate allocation concealment (10).”
ResultWood, L., Egger, M., Gluud, L. L., Schulz, K. F., Jüni, P., Altman, D. G., Gluud, C., Martin, R. M., Wood, A. J. G., & Sterne, J. A. C. (2008) · BMJ · doi:10.1136/bmj.39465.451748.ad · Cited by 2,538
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Shamseer, L., Moher, D., Clarke, M., Ghersi, D., Liberati, A., Petticrew, M., Shekelle, P., Stewart, L. A., & the PRISMA-P Group (2015) · BMJ · doi:10.1136/bmj.g7647 · Cited by 13,120
Savović, J., Jones, H. E., Altman, D. G., Harris, R. J., Jüni, P., Pildal, J., Als-Nielsen, B., Balk, E. M., Gluud, C., Gluud, L. L., et al. (2012) · Annals of Internal Medicine · doi:10.7326/0003-4819-157-6-201209180-00537 · Cited by 1,049
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Influence of trial sample size on treatment effect estimates: meta-epidemiological study
Dechartres, A., Trinquart, L., Boutron, I., & Ravaud, P. (2013) · BMJ · doi:10.1136/bmj.f2304 · Cited by 544
Self-citationPrevalence of anxiety in Parkinson's disease: A systematic review and meta‐analysis
Broen, M. P. G., Narayen, N. E., Kuijf, M. L., Dissanayaka, N. N. W., & Leentjens, A. F. G. (2016) · Movement Disorders · doi:10.1002/mds.26643 · Cited by 457
Metadata
- Authors
- Dechartres, A., Boutron, I., Trinquart, L., Charles, P., & Ravaud, P.
- Affiliations
- From U738 INSERM; Assistance Publique Hôpitaux de Paris (APHP), Hôpital Hôtel-Dieu; Université Paris Descartes, Sorbonne Paris Cité, Faculté de Médecine; and French Cochrane Centre, Paris, France, and Hôpital Foch, Suresnes, France.
- Inserm (FR)
- Venue
- Annals of Internal Medicine
- Publisher
- American College of Physicians
- Published
- 2011-07-05
- Volume
- 155
- Issue
- 1
- Pages
- 39-51
- ISSN
- 0003-4819 (ISSN-L)
- 1539-3704
- OpenAlex
- W2072619571
- Cited by
- 307
- References
- 72
- Citations by year
- 2026: 14 · 2025: 16 · 2024: 22 · 2023: 19 · 2022: 37 · 2021: 27 · 2020: 14 · 2019: 16 · 2018: 13 · 2017: 22 · 2016: 24 · 2015: 19 · 2014: 23 · 2013: 20 · 2012: 19
- FWCI
- 21.79
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Annals of Internal Medicine (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Social Sciences › Decision Sciences › Statistics, Probability and Uncertainty › Meta-analysis and systematic reviews
- Physical Sciences › Mathematics › Statistics and Probability › Statistical Methods in Clinical Trials
- Health Sciences › Nursing › Issues, ethics and legal aspects › Pharmaceutical industry and healthcare
- Keywords
- single-center trials, treatment effect estimates, meta-epidemiology, publication bias, allocation concealment, risk of bias, binary outcomes, sample size adjustment
- MeSH terms
- Humans, Sensitivity and Specificity, Meta-Analysis as Topic, Multicenter Studies as Topic, Epidemiologic Research Design, Bias, Odds Ratio, Randomized Controlled Trials as Topic, Treatment Outcome, Sample Size
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