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Potential impact on estimated treatment effects of information lost to follow-up in randomised controlled trials (LOST-IT): systematic review

BMJ 2012; 344 doi: (Published 18 May 2012) Cite this as: BMJ 2012;344:e2809
  1. Elie A Akl, associate professor12,
  2. Matthias Briel, assistant professor23,
  3. John J You, assistant professor24,
  4. Xin Sun, assistant professor25,
  5. Bradley C Johnston, assistant professor26,
  6. Jason W Busse, scientist27,
  7. Sohail Mulla, student2,
  8. Francois Lamontagne, adjunct professor8,
  9. Dirk Bassler, associate professor9,
  10. Claudio Vera, assistant professor10,
  11. Mohamad Alshurafa, student2,
  12. Christina M Katsios, student4,
  13. Qi Zhou, statistician2,
  14. Tali Cukierman-Yaffe, researcher411,
  15. Azim Gangji, assistant professor4,
  16. Edward J Mills, chair in global health12,
  17. Stephen D Walter, professor2,
  18. Deborah J Cook, professor24,
  19. Holger J Schünemann, department chair2413,
  20. Douglas G Altman, professor of statistics in medicine14,
  21. Gordon H Guyatt, professor24
  1. 1Departments of Medicine and Family Medicine, State University of New York at Buffalo, Buffalo, NY, USA
  2. 2Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, ON, Canada
  3. 3Basel Institute for Clinical Epidemiology and Biostatistics, University Hospital Basel, Basel, Switzerland
  4. 4Department of Medicine, McMaster University, Hamilton, ON
  5. 5Center for Health Research, Northwest, Kaiser Permanente Northwest, Portland, OR, USA
  6. 6Research Institute, Child Health Evaluative Sciences, Hospital for Sick Children, Toronto, ON, Canada
  7. 7Institute for Work and Health, Toronto, ON
  8. 8Centre de Recherche Clinique Étienne-Le Bel, Université de Sherbrooke, Sherbrooke, QC, Canada
  9. 9Centre for Paediatric Clinical Studies and Department of Neonatology, University Children’s Hospital Tuebingen, Tuebingen, Germany
  10. 10Division of Obstetrics and Gynaecology, Pontificia Universidad Católica de Chile, Santiago, Chile
  11. 11Gertner Institute for Epidemiology and Health Policy Research, Endocrinlogy Institute, Sheba Medical Center, Sackler school of Medicine, Tel-Aviv University, Tel-Aviv, Israel
  12. 12Faculty of Health Sciences, University of Ottawa, Ottawa, ON
  13. 13Institut für Medizinische Informatik und Biometrie, University of Freiburg, Germany
  14. 14Centre for Statistics in Medicine, University of Oxford, Oxford, UK
  1. Correspondence to: E A Akl, Department of Medicine, State University of New York at Buffalo, ECMC-CC 142, 462 Grider Street, Buffalo, NY 14215, USA elieakl{at}
  • Accepted 9 March 2012


Objective To assess the reporting, extent, and handling of loss to follow-up and its potential impact on the estimates of the effect of treatment in randomised controlled trials.

Design Systematic review. We calculated the percentage of trials for which the relative risk would no longer be significant under a number of assumptions about the outcomes of participants lost to follow-up.

Data sources Medline search of five top general medical journals, 2005-07.

Eligibility criteria Randomised controlled trials that reported a significant binary primary patient important outcome.

Results Of the 235 eligible reports identified, 31 (13%) did not report whether or not loss to follow-up occurred. In reports that did give the relevant information, the median percentage of participants lost to follow-up was 6% (interquartile range 2-14%). The method by which loss to follow-up was handled was unclear in 37 studies (19%); the most commonly used method was survival analysis (66, 35%). When we varied assumptions about loss to follow-up, results of 19% of trials were no longer significant if we assumed no participants lost to follow-up had the event of interest, 17% if we assumed that all participants lost to follow-up had the event, and 58% if we assumed a worst case scenario (all participants lost to follow-up in the treatment group and none of those in the control group had the event). Under more plausible assumptions, in which the incidence of events in those lost to follow-up relative to those followed-up is higher in the intervention than control group, results of 0% to 33% trials were no longer significant.

Conclusion Plausible assumptions regarding outcomes of patients lost to follow-up could change the interpretation of results of randomised controlled trials published in top medical journals.


  • We thank Ann Grifasi, Deborah Maddock Shelley Anderson, and Monica Owen for their administrative assistance and Aravin Duraik for developing the study electronic forms.

  • Contributors: EAA, MB, JJY, XS, FL, MA, EJM, SDW, DJC, HJS, DGA, and GHG were responsible for study conception and design. EAA, MB, JJY, XS, BCJ, JWB, SM, FL, DB, CV, MA, CMK, TC-Y, and AG acquired the data. EAA, QZ, and GHG analysed the data. EAA drafted the manuscript and is guarantor. All authors critically revised the manuscript and approved the final version.

  • Funding: This study was funded by Pfizer. The funder had no role in the study design, in the writing of the manuscript, or in the decision to submit this or future manuscripts for publication. MB is supported by a scholarship for advanced researchers from the Swiss National Foundation (PASMA-112951/1) and the Roche Research Foundation. JJY is supported by a career scientist award from the Ontario Ministry of Health and Long-Term Care. XS is supported by the National Natural Science Foundation of China (70703025). BCJ is supported by a SickKids Foundation postdoctoral fellowship. JWB is funded by a new investigator award from the CIHR and Canadian Chiropractic Research Foundation. AG is supported by the Kidney Foundation of Canada/Canadian Society of Nephrology fellowship award. DJC and EJM are supported by research chairs from CIHR. DGA is supported by Cancer Research UK.

  • 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; 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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