F Hoffmann1, F Andersohn. 1. Centre for Social Policy Research, Division Health Economics, Health Policy and Outcomes Research, University of Bremen, Ausser der Schleifmuehle 35-37, 28203 Bremen, Germany. hoffmann@zes.uni-bremen.de
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.
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.
Authors: S Matthaei; R Bierwirth; A Fritsche; B Gallwitz; H-U Häring; H-G Joost; M Kellerer; Ch Kloos; T Kunt; M Nauck; G Schernthaner; E Siegel; F Thienel Journal: Exp Clin Endocrinol Diabetes Date: 2009-10-29 Impact factor: 2.949
Authors: Stephan Martin; Hubert Kolb; Berthold Schneider; Lutz Heinemann; Christian Weber; Serge Kocher; Jacques K T Tshiananga; Werner A Scherbaum; Volker Lodwig Journal: Diabetes Technol Ther Date: 2009-04 Impact factor: 6.118