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Small studies may overestimate the effect sizes in critical care meta-analyses: a meta-epidemiological study
Open accessAbstract
INTRODUCTION: Small-study effects refer to the fact that trials with limited sample sizes are more likely to report larger beneficial effects than large trials. However, this has never been investigated in critical care medicine. Thus, the present study aimed to examine the presence and extent of small-study effects in critical care medicine. METHODS: Critical care meta-analyses involving randomized controlled trials and reported mortality as an outcome measure were considered eligible for the study. Component trials were classified as large (≥100 patients per arm) and small (<100 patients per arm) according to their sample sizes. Ratio of odds ratio (ROR) was calculated for each meta-analysis and then RORs were combined using a meta-analytic approach. ROR<1 indicated larger beneficial effect in small trials. Small and large trials were compared in methodological qualities including sequence generating, blinding, allocation concealment, intention to treat and sample size calculation. RESULTS: A total of 27 critical care meta-analyses involving 317 trials were included. Of them, five meta-analyses showed statistically significant RORs <1, and other meta-analyses did not reach a statistical significance. Overall, the pooled ROR was 0.60 (95% CI: 0.53 to 0.68); the heterogeneity was moderate with an I2 of 50.3% (chi-squared = 52.30; P = 0.002). Large trials showed significantly better reporting quality than small trials in terms of sequence generating, allocation concealment, blinding, intention to treat, sample size calculation and incomplete follow-up data. CONCLUSIONS: Small trials are more likely to report larger beneficial effects than large trials in critical care medicine, which could be partly explained by the lower methodological quality in small trials. Caution should be practiced in the interpretation of meta-analyses involving small trials.
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“It is possible that these findings were driven by the fact that smaller studies can sometimes overestimate effect sizes even when no true effect is present (Walum et al., 2016;Zhang et al., 2013).”
From Meta-analytic review of the effects of a single dose of intranasal oxytocin on threat processing in humans (2018) · cites this paper as Zhang et al., 2013
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1 retracted
Reilly, C. (2011) · British Journal of Anaesthesia · doi:10.1093/bja/aer068 · Cited by 26
RetractedCONSORT 2010 Statement: updated guidelines for reporting parallel group randomised trials
the CONSORT Group, Schulz, K. F., Altman, D. G., & Moher, D. (2010) · BMC Medicine · doi:10.1186/1741-7015-8-18 · Cited by 13,371
CONSORT 2010 Statement: updated guidelines for reporting parallel group randomised trials
Schulz, K. F., Altman, D. G., Moher, D., & for the CONSORT Group (2010) · BMJ · doi:10.1136/bmj.c332 · Cited by 9,329
Funnel plots for detecting bias in meta-analysis
Sterne, J. A. C., & Egger, M. (2001) · Journal of Clinical Epidemiology · doi:10.1016/s0895-4356(01)00377-8 · Cited by 3,779
Moher, D., Pham, B., Jones, A., Cook, D. J., Jadad, A. R., Moher, M., Tugwell, P., & Klassen, T. P. (1998) · The Lancet · doi:10.1016/s0140-6736(98)01085-x · Cited by 3,560
Wood, 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
Gluud, L. L., Villumsen, J., & Gluud, C. N. (2001) · Annals of Internal Medicine · doi:10.7326/0003-4819-135-11-200112040-00010 · Cited by 2,266
Egger, M., Jüni, P., Bartlett, C., Holenstein, F., & Sterne, J. (2003) · Health Technology Assessment · doi:10.3310/hta7010 · Cited by 1,181 · cited 1×
“However, this is an unsettled question and there are other studies supporting our finding [38,39].”
ResultImpact of the Pulmonary Artery Catheter in Critically Ill Patients
Shah, M. R., Hasselblad, V., Stevenson, L. W., Binanay, C. A., O’Connor, C. M., Sopko, G. S., & Califf, R. M. (2005) · JAMA · doi:10.1001/jama.294.13.1664 · Cited by 790
Chan, A.-W., & Altman, D. G. (2005) · BMJ · doi:10.1136/bmj.38356.424606.8f · Cited by 613 · cited 1×
“This effect can be explained, at least partly, by the combination of lower methodological quality of small studies and publication bias [2,3].”
BackgroundCorticosteroids in the Treatment of Severe Sepsis and Septic Shock in Adults
Annane, D., Bellissant, É., Bollaert, P., Briegel, J., Confalonieri, M., Gaudio, R. D., Keh, D., Kupfer, Y. Y., Oppert, M., & Meduri, G. U. (2009) · JAMA · doi:10.1001/jama.2009.815 · Cited by 572
Small study effects in meta-analyses of osteoarthritis trials: meta-epidemiological study
Nuesch, E., Trelle, S., Reichenbach, S., Rutjes, A. W. S., Tschannen, B., Altman, D. G., Egger, M., & Juni, P. (2010) · BMJ · doi:10.1136/bmj.c3515 · Cited by 559
Balk, E. M. (2002) · JAMA · doi:10.1001/jama.287.22.2973 · Cited by 478
Sterne, J. A. C., Jüni, P., Schulz, K. F., Altman, D. G., Bartlett, C., & Egger, M. (2002) · Statistics in Medicine · doi:10.1002/sim.1184 · Cited by 382
Delaney, A. P., Dan, A., McCaffrey, J., & Finfer, S. R. (2011) · Critical Care Medicine · doi:10.1097/ccm.0b013e3181ffe217 · Cited by 343
Blackwood, B., Alderdice, F. A., Burns, K. E. A., Cardwell, C. R., Lavery, G., & O’Halloran, P. D. (2011) · BMJ · doi:10.1136/bmj.c7237 · Cited by 333
Immunonutrition in critically ill patients: a systematic review and analysis of the literature
Marik, P. E., & Zaloga, G. P. (2008) · Intensive Care Medicine · doi:10.1007/s00134-008-1213-6 · Cited by 295
Tan, J. A., & Ho, K. M. (2010) · Intensive Care Medicine · doi:10.1007/s00134-010-1877-6 · Cited by 282
Kopterides, P., Siempos, I. Ι., Tsangaris, I., Tsantes, A. Ε., & Armaganidis, A. (2010) · Critical Care Medicine · doi:10.1097/ccm.0b013e3181f17bf9 · Cited by 243
Laupland, K. B., Kirkpatrick, A. W., & Delaney, A. P. (2007) · Critical Care Medicine · doi:10.1097/01.ccm.0000295312.13466.1c · Cited by 235
Siempos, I. I., Ntaidou, T. K., & Falagas, M. E. (2010) · Critical Care Medicine · doi:10.1097/ccm.0b013e3181c8fe4b · Cited by 204
Barkun, A. N., Bardou, M., Pham, C. Q. D., & Martel, M. (2012) · The American Journal of Gastroenterology · doi:10.1038/ajg.2011.474 · Cited by 162
The Timing of Tracheotomy in Critically Ill Patients Undergoing Mechanical Ventilation
Wang, F., Wu, Y., Bo, L., Lou, J., Zhu, J., Chen, F., Li, J., & Deng, X. (2011) · CHEST Journal · doi:10.1378/chest.11-2024 · Cited by 149
Abroug, F., Ouanes-Besbes, L., Dachraoui, F., Ouanes, I., & Brochard, L. J. (2011) · Critical Care · doi:10.1186/cc9403 · Cited by 142
Afshari, A., Brok, J. S., Møller, A. M., & Wetterslev, J. (2011) · Anesthesia & Analgesia · doi:10.1213/ane.0b013e31820bd185 · Cited by 140
Neto, A. S., Nassar, A. P., Cardoso, S. O., Manetta, J. A., Pereira, V. G., Espósito, D. C., Damasceno, M. C. T., & Russell, J. A. (2012) · Critical Care · doi:10.1186/cc11469 · Cited by 128
Norepinephrine or Dopamine for Septic Shock
Vasu, T. S., Cavallazzi, R., Hirani, A., Kaplan, G., Leiby, B. E., & Marik, P. E. (2011) · Journal of Intensive Care Medicine · doi:10.1177/0885066610396312 · Cited by 107
Pileggi, C., Bianco, A., Flotta, D., Nobile, C. G. A., & Pavía, M. (2011) · Critical Care · doi:10.1186/cc10285 · Cited by 105
Phoenix, S. I., Paravastu, S. C. V., Columb, M. O., Vincent, J., & Nirmalan, M. (2009) · Anesthesiology · doi:10.1097/aln.0b013e31819fae06 · Cited by 101
Burns, K. E. A., Adhikari, N. K. J., Slutsky, A. S., Guyatt, G. H., Villar, J., Zhang, H., Zhou, Q. X., Cook, D. J., Stewart, T. E., & Meade, M. O. (2011) · PLoS ONE · doi:10.1371/journal.pone.0014623 · Cited by 99
Afshari, A., Wetterslev, J., Brok, J. S., & Møller, A. M. (2007) · BMJ · doi:10.1136/bmj.39398.682500.25 · Cited by 94
Siersma, V., Als-Nielsen, B. E. T., Chen, W., Hilden, J., Gluud, L. L., & Gluud, C. N. (2006) · Statistics in Medicine · doi:10.1002/sim.2752 · Cited by 83
Subglottic secretion drainage for preventing ventilator-associated pneumonia
Wang, F., Bo, L., Tang, L., Lou, J., Wu, Y., Chen, F., Li, J., & Deng, X. (2012) · The Journal of Trauma: Injury, Infection, and Critical Care · doi:10.1097/ta.0b013e318247cd33 · Cited by 72
Augustes, R., & Ho, K. M. (2011) · Anaesthesia and Intensive Care · doi:10.1177/0310057x1103900310 · Cited by 65
Landoni, G., Mizzi, A., Biondi‐Zoccai, G., Bignami, E. G., Prati, P. L., Ajello, V., Marino, G., Guarracino, F., & Zangrillo, A. (2010) · PubMed · Cited by 59
Micronutrient supplementation for critically ill adults: A systematic review and meta-analysis
Visser, J., Labadarios, D., & Blaauw, R. (2011) · Nutrition · doi:10.1016/j.nut.2010.12.009 · Cited by 52
Zarychanski, R., Turgeon, A. F., Fergusson, D. A., Cook, D. J., Hébert, P. C., Bagshaw, S. M., Monsour, D. A., & McIntyre, L. (2009) · PubMed Central · Cited by 47
Puskarich, M. A., Runyon, M. S., Trzeciak, S., Kline, J. A., & Jones, A. E. (2009) · The Journal of Clinical Pharmacology · doi:10.1177/0091270009334375 · Cited by 23
Zhang, Z., Xu, X., & Hongyang, Z. (2010) · Journal of Critical Care · doi:10.1016/j.jcrc.2010.05.030 · Cited by 21
Zarychanski, R., Turgeon, A. F., Fergusson, D. A., Cook, D. J., Hébert, P. C., Bagshaw, S. M., Monsour, D. A., & McIntyre, L. (2009) · PubMed Central · Cited by 18
Shan, L., Hao, P., & Chen, Y. (2011) · The Journal of Trauma: Injury, Infection, and Critical Care · doi:10.1097/ta.0b013e3182250515 · Cited by 13
Flagged first, then by citations
Research works printed but not linked: 1
- Zarychanski R, Turgeon AF, Fergusson DA, Cook DJ, Hébert P, Bagshaw SM, Monsour D, McIntyre L: Renal outcomes and mortality following hydroxyethyl starch resuscitation of critically ill patients: systematic review and meta-analysis of randomized trials. Open Med 2009, 3: e196-209.
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The ARISE Investigators and the ANZICS Clinical Trials Group (2014) · New England Journal of Medicine · doi:10.1056/nejmoa1404380 · Cited by 2,055
Guidelines for reporting meta-epidemiological methodology research
Murad, M. H., & Wang, Z. (2017) · Evidence Based Medicine · doi:10.1136/ebmed-2017-110713 · Cited by 515
Ludyga, S., Gerber, M., Pühse, U., Looser, V. N., & Kamijo, K. (2020) · Nature Human Behaviour · doi:10.1038/s41562-020-0851-8 · Cited by 522
Effectiveness, Core Elements, and Moderators of Response of Cognitive Remediation for Schizophrenia
Vita, A., Barlati, S., Ceraso, A., Nibbio, G., Ariu, C., Deste, G., & Wykes, T. (2021) · JAMA Psychiatry · doi:10.1001/jamapsychiatry.2021.0620 · Cited by 503
Risk factors for child sexual abuse victimization: A meta-analytic review.
Assink, M., van der Put, C. E., Meeuwsen, M. W. C. M., de Jong, N. M., Oort, F. J., Stams, G. J. J. M., & Hoeve, M. (2019) · Psychological bulletin · doi:10.1037/bul0000188 · Cited by 322
Metadata
- Authors
- Zhang, Z., Xu, X., & Ni, H.
- Affiliations
- Jinhua Central Hospital (CN)
- Corresponding author
- Zhang, Zhongheng
- Venue
- Critical Care
- Published
- 2013-01-09
- Volume
- 17
- Issue
- 1
- Pages
- R2-R2
- ISSN
- 1364-8535 (ISSN-L)
- PMC
- PMC4056100
- OpenAlex
- W2066676890
- Cited by
- 295
- References
- 41
- Citations by year
- 2026: 16 · 2025: 18 · 2024: 24 · 2023: 26 · 2022: 30 · 2021: 27 · 2020: 27 · 2019: 27 · 2018: 22 · 2017: 20 · 2016: 19 · 2015: 14 · 2014: 17 · 2013: 8
- FWCI
- 21.05
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Critical Care (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- 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
- Physical Sciences › Mathematics › Statistics and Probability › Statistical Methods in Epidemiology
- Keywords
- small-study effects, sample size, effect size overestimation, mortality, methodological quality of trials, allocation concealment, blinding, incomplete follow-up, meta-epidemiology
- MeSH terms
- Critical Care, Humans, Epidemiologic Studies, Randomized Controlled Trials as Topic
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