Article type
Year
Abstract
Background: The proof of a comparable efficacy or harm of 2 or more treatments is a well known problem in randomized clinical trials (RCTs). It has recieved widespread attention in the past. Such trials are called 'equivalence trials' (ETs) or 'non-inferiority trials' (N-ITs). An essential issue in planning ETs or N-ITs is the pre-specification of the 'irrelevant difference', which quantifies the amount of difference or inferiority which is to be considered tolerable. Comparability can then be assumed, if a difference larger than this quantity can be excluded by a confidence interval for the treatment difference or an appropriate statistical test. It is obvious that the equivalence or non-inferiority problem also arises in systematic reviews (SRs). Astonishingly, thus far, this issue seems to be neglected in the methodological literature with regard to SRs.
Objectives: It was the aim of our study to get an impression whether the equivalence or non-inferiority problem is an issue in SRs.
Methods: A random sample of 100 SRs was drawn from the Cochrane Library, 25 each for the periods 1998-1999, 2000-2001, 2002-2003, and 2004-2005. To be included, the reviews had to deal with therapeutic interventions, and the reviews had to summarize the results of at least 5 single trials. Protocols and /or updates were excluded. Two independent reviewers examined (i) whether equivalence or non-inferiority was stated as a problem of the reviews themselves, and (ii) whether irrelevant differences were pre-specified.
Results: (i) Equivalence or non-inferiority was stated as a problem of the review itself in only 4 reviews. (ii) An irrelevant difference was pre-defined in one review.
Conclusions: In SRs, equivalence or non-inferiority is only rarely mentioned as a problem of the reviews themselves. While we found several statements in regard to which differences between treatments were regarded as 'comparable', an irrelevant difference was pre-defined in only one review, as it is a part of good statistical practice in RCTs, when it is the aim to show comparability. Methodological advice is urgently necessary when considering how to deal with this issue in SRs.
Objectives: It was the aim of our study to get an impression whether the equivalence or non-inferiority problem is an issue in SRs.
Methods: A random sample of 100 SRs was drawn from the Cochrane Library, 25 each for the periods 1998-1999, 2000-2001, 2002-2003, and 2004-2005. To be included, the reviews had to deal with therapeutic interventions, and the reviews had to summarize the results of at least 5 single trials. Protocols and /or updates were excluded. Two independent reviewers examined (i) whether equivalence or non-inferiority was stated as a problem of the reviews themselves, and (ii) whether irrelevant differences were pre-specified.
Results: (i) Equivalence or non-inferiority was stated as a problem of the review itself in only 4 reviews. (ii) An irrelevant difference was pre-defined in one review.
Conclusions: In SRs, equivalence or non-inferiority is only rarely mentioned as a problem of the reviews themselves. While we found several statements in regard to which differences between treatments were regarded as 'comparable', an irrelevant difference was pre-defined in only one review, as it is a part of good statistical practice in RCTs, when it is the aim to show comparability. Methodological advice is urgently necessary when considering how to deal with this issue in SRs.