Study protocol

LOST to follow-up Information in Trials (LOST-IT): a protocol on the potential impact

Elie A Akl¹ , Matthias Briel^2,3 , John J You^2,4 , Francois Lamontagne^2,5 , Azim Gangji⁴ , Tali Cukierman-Yaffe⁶ , Mohamad Alshurafa² , Xin Sun^2,7 , Kara A Nerenberg⁴ , Bradley C Johnston⁸ , Claudio Vera⁹ , Edward J Mills¹⁰ , Dirk Bassler¹¹ , Arturo Salazar¹² , Neera Bhatnagar¹³ , Jason W Busse^2,14 , Zara Khalid² , SD Walter² , Deborah J Cook^2,4 , Holger J Schünemann^2,15 , Douglas G Altman¹⁶ and Gordon H Guyatt^2,4

¹  Departments of Medicine and Family Medicine, State University of New York at Buffalo, Buffalo, USA

²  Department of Biostatistics and Clinical Epidemiology, McMaster University, Hamilton, Canada

³  Basel Institute for Clinical Epidemiology, University Hospital Basel, Basel, Switzerland

⁴  Department of Medicine, McMaster University, Hamilton, Canada

⁵  Department of Medicine, University of Sherbrooke, Sherbrooke, Canada

⁶  Gertner Institute for Epidemiology & Health Policy Research, Sheba medical center, Sackler school of Medicine, Tel -Aviv University, Tel-Aviv, Israel

⁷  Department of Clinical Epidemiology, West China Hospital, Sichuan University, Chengdu, PR China

⁸  Department of Medicine, University of Alberta, Edmonton, Canada

⁹  Department of Obstetrics & Gynecology, Pontificia Universidad Católica de Chile, Santiago, Chile

¹⁰  Centre for International Health and Human Rights Studies, North York, Canada

¹¹  Department of Neonatology, University Children's Hospital, Tuebingen, Germany

¹²  Department of Internal Medicine, Wayne State University, Detroit, USA

¹³  Health Sciences Library, McMaster University, Hamilton, Canada

¹⁴  The Institute for Work & Health, Toronto, Ontario, Canada

¹⁵  Department of Epidemiology, Italian National Cancer Institute Regina Elena, Rome, Italy

¹⁶  Centre for Statistics in Medicine, University of Oxford, Oxford, UK

author email corresponding author email

Trials 2009, 10:40doi:10.1186/1745-6215-10-40

Published:	11 June 2009

Abstract

Background

Incomplete ascertainment of outcomes in randomized controlled trials (RCTs) is likely to bias final study results if reasons for unavailability of patient data are associated with the outcome of interest. The primary objective of this study is to assess the potential impact of loss to follow-up on the estimates of treatment effect. The secondary objectives are to describe, for published RCTs, (1) the reporting of loss to follow-up information, (2) the analytic methods used for handling loss to follow-up information, and (3) the extent of reported loss to follow-up.

Methods

We will conduct a systematic review of reports of RCTs recently published in five top general medical journals. Eligible RCTs will demonstrate statistically significant effect estimates with respect to primary outcomes that are patient-important and expressed as binary data. Teams of 2 reviewers will independently determine eligibility and extract relevant information from each eligible trial using standardized, pre-piloted forms. To assess the potential impact of loss to follow-up on the estimates of treatment effect we will, for varying assumptions about the outcomes of participants lost to follow-up (LTFU), calculate (1) the percentage of RCTs that lose statistical significance and (2) the mean change in effect estimate across RCTs. The different assumptions we will test are the following: (1) none of the LTFU participants had the event; (2) all LTFU participants had the event; (3) all LTFU participants in the treatment group had the event; none of those in the control group had it (worst case scenario); (4) the event incidence among LTFU participants (relative to observed participants) increased, with a higher relative increase in the intervention group; and (5) the event incidence among LTFU participants (relative to observed participants) increased in the intervention group and decreased in the control group.

Discussion

We aim to make our objectives and methods transparent. The results of this study may have important implications for both clinical trialists and users of the medical literature.