Reporting of loss to follow-up information in randomised controlled trials with time-to-event outcomes: a literature survey

Abstract

BackgroundTo assess the reporting of loss to follow-up (LTFU) information in articles on randomised controlled trials (RCTs) with time-to-event outcomes, and to assess whether discrepancies affect the validity of study results.MethodsLiterature survey of all issues of the BMJ, Lancet, JAMA, and New England Journal of Medicine published between 2003 and 2005. Eligible articles were reports of RCTs including at least one Kaplan-Meier plot. Articles were classified as "assessable" if sufficient information was available to assess LTFU. In these articles, LTFU information was derived from Kaplan-Meier plots, extracted from the text, and compared. Articles were then classified as "consistent" or "not consistent". Sensitivity analyses were performed to assess the validity of study results.Results319 eligible articles were identified. 187 (59%) were classified as "assessable", as they included sufficient information for evaluation; 140 of 319 (44%) presented consistent LTFU information between the Kaplan-Meier plot and text. 47 of 319 (15%) were classified as "not consistent". These 47 articles were included in sensitivity analyses. When various imputation methods were used, the results of a chi2-test applied to the corresponding 2 × 2 table changed and hence were not robust in about half of the studies.ConclusionsLess than half of the articles on RCTs using Kaplan-Meier plots provide assessable and consistent LTFU information, thus questioning the validity of the results and conclusions of many studies presenting survival analyses. Authors should improve the presentation of both Kaplan-Meier plots and LTFU information, and reviewers of study publications and journal editors should critically appraise the validity of the information provided.

Reporting of Lost to Follow-Up and Treatment Discontinuation in Pharmacotherapy and Device Trials in Chronic Heart Failure

“…[77][78][79][80][81][82] LTFU introduces bias if the characteristics of participants LTFU differ between the randomized groups and the characteristics that differ are related to the trial's outcomes, especially if the proportion of participants LTFU differs between treatment groups. [77][78][79][80][81][82] For example, patients who are sicker at baseline are more likely to experience worsening of their condition; worsening may lead to withdrawal from the trial and the patient may die. Both worsening and death may be important outcomes in the trial and, if missing, will result in the trial giving an incomplete report of the true picture of what happens to patients with the condition.…”

Addressing Dichotomous Data for Participants Excluded from Trial Analysis: A Guide for Systematic Reviewers

“…Authors implementing our suggested methods may be challenged by the fact that many trials either do not clearly report the number or the reasons of participants with missing data [14].…”

How to optimize participant retention and complete follow-up in surgical research

“…Regardless of the reason, the participants who drop out or who are lost to follow-up represent an atypical subgroup. 6,7,11 The systematic differences between the discontinuers and continuers threaten the credibility as well as the generalizability of the findings. 2 Many losses to follow-up particularly increase the possibility of a type-2 error (i.e., false-negative result), undermining the study power.…”

“…While excluding these patients may make the study less generalizable, including the patients poses a potential risk to the completeness of the data. Including a "run-in" or "wash-out" period in clinical trials 11,16 in which patients complete 1-2 visits before inclusion in the study, can help differentiate compliant from noncompliant participants. Further, during the runin period, collecting feedback on the intervention burden (i.e., issues related to the intervention that may affect adherence and compliance, such as injections or multiple trips to hospital) can assist to further resolve the noncompliance issue.…”