Intravenous proton pump inhibitors for stress ulcer prophylaxis in critically ill patients: determining statistical equivalence according to evidence-based methods

Abstract

Our analysis involved 8 randomized trials for 851 patients. Two comparisons were made (pantoprazole vs. H2-receptor antagonists and omeprazole vs. H2-receptor antagonists). The following RDs were estimated: pantoprazole, RD = -1.2%, 95% CI: -3.5% to +1.2%; omeprazole, RD = -3.0%, 95% CI: -7.2% to +1.3%. The 95% CIs confidence intervals for RDs remained within the ± 6% margin. These results indicate that intravenous pantoprazole and intravenous omeprazole are equivalent, Conclusion: These two PPIs, when administered by intravenous route, are equivalent according to reasonable equivalence margins. This conclusion can be the basis to develop local acquisition tenders on these drugs. One advantage of this approach is that the feasibility of administrative decisions can directly be tested on clinical grounds and on the basis of standard evidence-based methods.

Testing the therapeutic equivalence of novel oral anticoagulants for thromboprophylaxis in orthopedic surgery and for prevention of stroke in atrial fibrillation

“…According to our results (in particular, the two analyses presented in Figures 1 and 2), rivaroxaban and apixaban proved to be equivalent in their effectiveness for thromboprophylaxis in orthopedic surgery, while dabigatran, rivaroxaban, apixaban, and edoxaban proved to be equivalent in their effectiveness for stroke prevention in atrial fibrillation. These demonstrations of equivalence suffer from the same limitations already pointed out in previous studies [1,2,3,4,5,6,7]. For example, margins continue to be a point of controversy in the overall area of equivalence studies [11,12,13,14,15,16]; furthermore, in the case of our analysis on NOACs, one might not agree from a clinical perspective on the magnitude of the margins (± 7.7% and ± 2.5% for the endpoints of thromboprophylaxis and stroke prevention, respectively).…”

“…In Italy, there has been a renewed interest in defining the criteria for therapeutic equivalence because, at the end of 2012, a national regulation was issued ("decreto Balduzzi" [7,8]) concerning the acquisition tenderings run by our NHS. According to this regulation, when these tenderings are aimed at drugs that belong to the same pharmacological class, a preventive authorization must be obtained from our National Medicines Agency to certify that the agents under examination are therapeutically equivalent.…”

“…The "best" paper(s) for the purposes of our analyses were identified through a simplified procedure that we had already adopted in a previous paper [7]. Firstly, we identified all reviews/meta-analyses that were considered eligible for our purposes (namely: a first subset of reviews suitable for the indication of thromboprophylaxis and a second subset of reviews suitable for atrial fibrillation), and we retrieved their full text.…”

“…Demonstrations of therapeutic equivalence have obvious clinical implications. However, these findings also have important practical consequences because hospital acquisition tenderings can be conducted more selectively in cases where equivalence has been demonstrated across different agents of the same pharmacological class [6,7].…”

Biological drugs for the treatment of rheumatoid arthritis by the subcutaneous route: interpreting efficacy data to assess statistical equivalence

“…On the other hand, the concepts of therapeutic equivalence and noninferiority have been widely debated in the scientific literature of the last years, particularly in the context of randomized controlled trials (RCTs) and meta-analyses. As a result, the statistical methodology for equivalence and noninferiority testing is now mature [Ahn et al 2013;Christensen, 2007;Tunes da Silva et al 2009] and in fact these techniques are increasingly being used in evidence-based analyses (especially those focused on comparative effectiveness) [Messori et al 2014a[Messori et al , 2014b[Messori et al , 2014c[Messori et al , 2014dMaratea et al 2014].…”