Description

While an ideal clinical trial will have no patients lost to follow-up, almost all studies will have some patient lost to follow-up. It is important to determine if this loss will significantly impact the conclusions of the study.

"5 and 20 Rule" (Sackett et al, 2000): While easy to remember, it may oversimplify the problem if the selected outcome is infrequent.

 Loss to Follow-Up Interpretation < 5% conclusions probably acceptable 5 - 20% intermediate > 20% validity of conclusions seriously open to question

Rule of Thumb of Schulz and Grimes: The loss to follow-up should not exceed the outcome event rate.

Estimating the possible impact of missing patients lost to follow-up (Sackett et al, 1991):

(1) Calculate the fraction of patients who developed a particular outcome:

fraction as measured =

= (patients with outcome) / (all patients not lost to follow-up)

(2) Calculate the possible outcome range if follow-up patients were available:

best case scenario =

= fraction of patients if none of the follow-up patients had the outcome =

= (patients with outcome) / ((all patients not lost to follow-up) + (patients lost to follow-up)) =

= (patients with outcome) / (patients initially enrolled)

worst case scenario =

= fraction of patients if all of the follow-up patients had the outcome =

= ((patients with outcome) + (patients lost to follow-up)) / ((all patients not loss to follow-up) + (patients lost to follow-up))

= ((patients with outcome) + (patients lost to follow-up)) / (patients initially enrolled)

(3) If the fraction as measured is similar to the two assumed fractions, then impact of the patients lost to follow-up is probably not great.

(4) If the there is a "significant" difference between the two fractions including patients lost to follow-up, then the outcome reported may not be valid.

NOTE: "Significant" is not defined, but a ratio of the fractions from the worst case to best case scenarios may be a simple measure. The acceptable example had a ratio of 1.1 while the unacceptable example had a ratio of 7.1. Probably a ratio < 1.5 is good and a ratio > 4 is high.