Y Yazici1, N M Adler, H Yazici. 1. Department of Medicine, Division of Rheumatology, New York University, Hospital for Joint Diseases, USA. yusuf.yazici@nyumc.org
Abstract
OBJECTIVES: Many randomized clinical trials (RCTs) are labelled efficacy and safety while due consideration for power is provided only for efficacy outcomes. This in turn necessitates a discussion of the inadequacy of sample size (type II error) for identifying harm. This is particularly important in RCTs of TNF inhibitors as harm related to these agents is still a matter of debate. METHODS: PubMed was searched for all RCTs published examining TNF inhibitors in RA, PsA and AS. Only original study reports were surveyed for whether: (i) they were labelled as efficacy, safety or both; (ii) the methods sections included safety as a primary or secondary end point; (iii) power calculations were adequately explained; (iv) statistical tests of significance were given for harm; and finally (v) any discussion of type II error for harm was present. RESULTS: Of the 34 articles surveyed, 24 (71%) were labelled as efficacy and safety. Among these, 23 (96%) did not include safety as a formal primary or secondary end point. In only 2/24 (8%) power calculations were given for safety. Finally, in only 3/22 (14%) any discussion about the inadequate sample size (type II error) for detecting harm could be found. CONCLUSIONS: Most reports of RCTs of TNF inhibitors in rheumatological diseases are inappropriately labelled as addressing efficacy and safety. Their lack of power in detecting harm is not adequately discussed, either.
OBJECTIVES: Many randomized clinical trials (RCTs) are labelled efficacy and safety while due consideration for power is provided only for efficacy outcomes. This in turn necessitates a discussion of the inadequacy of sample size (type II error) for identifying harm. This is particularly important in RCTs of TNF inhibitors as harm related to these agents is still a matter of debate. METHODS: PubMed was searched for all RCTs published examining TNF inhibitors in RA, PsA and AS. Only original study reports were surveyed for whether: (i) they were labelled as efficacy, safety or both; (ii) the methods sections included safety as a primary or secondary end point; (iii) power calculations were adequately explained; (iv) statistical tests of significance were given for harm; and finally (v) any discussion of type II error for harm was present. RESULTS: Of the 34 articles surveyed, 24 (71%) were labelled as efficacy and safety. Among these, 23 (96%) did not include safety as a formal primary or secondary end point. In only 2/24 (8%) power calculations were given for safety. Finally, in only 3/22 (14%) any discussion about the inadequate sample size (type II error) for detecting harm could be found. CONCLUSIONS: Most reports of RCTs of TNF inhibitors in rheumatological diseases are inappropriately labelled as addressing efficacy and safety. Their lack of power in detecting harm is not adequately discussed, either.
Authors: An-Wen Chan; Jennifer M Tetzlaff; Peter C Gøtzsche; Douglas G Altman; Howard Mann; Jesse A Berlin; Kay Dickersin; Asbjørn Hróbjartsson; Kenneth F Schulz; Wendy R Parulekar; Karmela Krleza-Jeric; Andreas Laupacis; David Moher Journal: BMJ Date: 2013-01-08