Hello again!First of all, thank you very much for the prompt reply!I am using the definitions for non-inferiority and equivalence provided by the extension of the CONSORT statement for these trials (Piaggio G, Elbourne DR, Altman DG, Pocock SJ, Evans SJ. Reporting of noninferiority and equivalence randomized trials: an extension of the CONSORT statement. JAMA 2006; 295(10):1152-1160.PMID: 16522836):"Equivalence trials aim to determine whether one (typically new) intervention is therapeutically similar to another, usually an existing treatment. We use new to refer to the treatment under test, and the comparison or reference treatment is often called an active control.Noninferiority trials seek to determine whether a new treatment is no worse than a reference treatment. Because proof of exact equality is impossible, a prestated margin of noninferiority (∆) for the treatment effect in a primary patient outcome is defined. Equivalence trials are very similar, except that equivalence is defined as the treatment effect being between -∆ and ∆".
However, I know it is difficult to define in the review protocol what will be the non-inferiority margin because the population included in the primary studies (and the control event risk) will vary.
I agree with Mike Bennett: non-inferiority or equivalence are related to the hypothesis under test (and have implications in the analysis and in the determination of the sample size). For this reason, I won´t consider the aim of each primary study (superiority, non-inferiority...) as an eligibility criteria in my review (it is not a factor influencing in the risk of bias of the primary studies).However I think the issue is relevant and must be detailed in the protocol (most of Cochrane protocols don´t give details about it). There are several sections in a Cochrane protocol where some information should be stated, for example:-the "Objectives" section: the main objective of the review is determining superiority, non-inferiority or equivalence? this information should be specified?,-the section "Dealing with missing data", where we should define which will be our first choice of analysis strategy, intention-to-treat or per-protocol.Moreover, I have some doubts about including in the same meta-analysis these three types of trials, mainly because the interpretation of the results can be different depending on the hypothesis of the included studies. For example, how to formulate conclusions based on a meta-analysis that included superiority and non-inferiority trials? (the same result may be interpreted in different ways, depending on the hypothesis (superiority or non-inferiority)). Should I make two meta-analysis (one with superiority trials and another one with non-inferiority trials)?Thank you very much for all the replies by the list members; I will summarize them as soon as possible and post them to the list!.Jesús
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Jesús López Alcalde
Grupo Cochrane Iberoamericano de Seguridad del Paciente
Centro Cochrane Iberoamericano (CCIb)
Telf. (0034) 913 089 400 (Ext. 657)
Telf. móvil: (0034) 633 217 736
Jesús López Alcalde
Systematic Reviews on Patient Safety Iberoamerican Group
Iberoamerican Cochrane Centre
Phone (0034) 913 089 400 (Ext. 657)
Cel.: (0034) 633 217 736