Lost to Follow-up

Lead Author(s): Jeff Martin, MD

Main Threat to Validity in a Cohort Study

"What is the effect of subjects who are lost to follow-up on the inferences generated by a cohort study?"

This is the key element in conducting a good cohort study or clinical trial. There are, of course, other threats to validity but they are related to elements such as measurement and confounding.

Subjects Lost During Follow-up

If losses are random, only power is affected. If disease incidence is research question, losses related to outcome bias results. If association of risk factor to disease is focus, losses bias results only if related to both outcome and the risk factor.

Crucial Issues in Who Is Lost to Follow-up

In the diagram below we ask what are the crucial issues in who is leaving cohort: 0504_diagram.JPG

Determining Answers to Crucial Issues

In practice, it may often not be possible to answer these questions in a cohort study for the simple reason that subjects who are lost or refuse to participate further may not be available to supply the answers.

At a minimum you need to attempt to answer them with whatever information you do have about the characteristics of those leaving the cohort by comparing those characteristics with those you retain.

Another strategy to guard the validity of your result is to do a sensitivity analysis in which you assume a worst case scenario for those you have lost and see how much it could affect your findings.

Preventing Losses to Follow-up

Prevent losses to follow-up:

Select those most willing to participate (internal validity before generalizability).

Obtain comprehensive contact information. At a bare minimum, obtain: Be sure to engage participants while in follow-up.

Managing Losses to Follow-up

Manage losses to follow-up by: It is important to search for a sample of those lost to compare them with those still on-study and see if there are any systematic problems.