Combined bias suppression in single-arm therapy studies.

Rationale, Aims And Objectives: For therapy evaluation studies, control groups are sometimes not feasible. In single-arm studies, various bias factors apart from the test therapy can affect clinical outcomes. The objective of this analysis was to improve the methods to minimize bias in single-arm studies.

Method: We present a procedure for combined suppression of several bias factors, using two methods: sample restriction to patients unaffected by bias, and score adjustment. The procedure was used for a secondary analysis of disease score (doctors' global rating, 0-10) in a cohort of patients receiving anthroposophic therapies for chronic diseases. Four bias factors were suppressed stepwise: attrition bias (by replacing missing values with the baseline value carried forward), bias from natural recovery (by sample restriction to patients with disease duration of >/=12 months), regression to the mean due to symptom-driven self-selection (by replacing baseline scores with scores three months before enrolment) and bias from adjunctive therapies (by sample restriction to patients not using adjunctive therapies).

Results: In the cohort analysed, these four bias factors could together explain a maximum of 37% of the 0- to 6-month improvement of disease score.

Conclusion: Combined bias suppression, using sample restriction and score adjustment, is a transparent procedure to minimize bias in single-arm therapy studies. Further applicability of the procedure should be tested in future studies.