Immortal time bias and survival in patients who self-monitor blood glucose in the Retrolective Study: self-monitoring of Blood Glucose and Outcome in Patients with Type 2 Diabetes (ROSSO)

Abstract

Aims/hypothesis: In the February 2006 issue of Diabetologia, the observational Retrolective Study: Self-monitoring of Blood Glucose and Outcome in Patients with Type 2 Diabetes (ROSSO) reported a 51% reduction in the risk of all-cause mortality in patients with type 2 diabetes who performed self-monitoring of blood glucose (SMBG). However, these impressive benefits conflict with results from observational studies and randomised controlled trials. We aimed to show that these findings are caused by a flawed design that introduced immortal time bias.

Methods: We illustrate the bias in the ROSSO study and demonstrate that it is large enough to completely explain the apparently protective effect of SMBG on all-cause mortality.

Results: In the ROSSO study, patients were classified as exposed to SMBG for their whole follow-up time if they performed self-monitoring for at least 1 year during the study period. Thus, the time between cohort entry and the date after 1 year self-monitoring was performed is unavoidably 'immortal' for patients with SMBG. Patients had to survive at least 1 year to be classified as exposed to this intervention and were artificially 'protected' from death. Based on published information, the total amount of misclassified immortal person-time in the SMBG group is at least 5,082 of 9,248 person-years at risk (55%). After re-classification of immortal person-time as unexposed, the unadjusted relative risk changed from 0.59 to 1.95.

Conclusions/interpretation: The apparently protective effect of SMBG on all-cause mortality observed in the ROSSO study is completely explained by immortal time bias.