Basic characteristics of included studies.

<p>Basic characteristics of included studies.</p

Deficient Reporting and Interpretation of Non-Inferiority Randomized Clinical Trials in HIV Patients: A Systematic Review

<div><p>Objectives</p><p>Non-inferiority (NI) randomized clinical trials (RCTs) commonly evaluate efficacy of new antiretroviral (ARV) drugs in human immunodeficiency virus (HIV) patients. Their reporting and interpretation have not been systematically evaluated. We evaluated the reporting of NI RCTs in HIV patients according to the CONSORT statement and assessed the degree of misinterpretation of RCTs when NI was inconclusive or not established.</p><p>Design</p><p>Systematic review.</p><p>Methods</p><p>PubMed, Web of Science, and Scopus were reviewed until December 2011. Selection and extraction was performed independently by three reviewers.</p><p>Results</p><p>Of the 42 RCTs (n = 21,919; range 41–3,316) selected, 23 were in ARV-naïve and 19 in ARV-experienced patients. Twenty-seven (64%) RCTs provided information about prior RCTs of the active comparator, and 37 (88%) used 2-sided CIs. Two thirds of trials used a NI margin between 10 and 12%, although only 12 explained the method to determine it. Blinding was used in 9 studies only. The main conclusion was based on both intention-to-treat (ITT) and per protocol (PP) analyses in 5 trials, on PP analysis only in 4 studies, and on ITT only in 31 studies. Eleven of 16 studies with NI inconclusive or not established highlighted NI or equivalence, and distracted readers with positive secondary results.</p><p>Conclusions</p><p>There is poor reporting and interpretation of NI RCTs performed in HIV patients. Maximizing the reporting of the method of NI margin determination, use of blinding and both ITT and PP analyses, and interpreting negative NI according to actual primary findings will improve the understanding of results and their translation into clinical practice.</p></div

Forest plot showing efficacy of 5-NIs in the treatment of giardiasis; stratified by type of drug.

<p>Forest plot showing efficacy of 5-NIs in the treatment of giardiasis; stratified by type of drug.</p

Funnel plot assessing publication bias.

<p>Funnel plot assessing publication bias.</p

Flow diagram of selected studies.

<p>Flow diagram of selected studies.</p

Forest plot showing efficacy of 5-NIs in the treatment of giardiasis.

<p>Forest plot showing efficacy of 5-NIs in the treatment of giardiasis.</p

Study characteristics of non-inferiority trials in ARV-experienced patients.

*<p>81% ARV-experienced patients in the study; LLOQ = Lower limit of quantitation; 3TC = Lamivudine; ZDV = Zidovudine; APV = Amprenavir; RTV = Ritonavir; FTC = Emtricitabine; d4T = Stavudine; DRV = Darunavir; LPV = Lopinavir; RAL = Raltegravir; T-20 =  Enfuvirtide; TDF = Tenofovir DF; EFV = Efavirenz; ddI = Didanosine.</p

Study characteristics of non-inferiority trials in ARV-naive patients.

<p>Plac = placebo; TLOVR = time to loss of virologic response; TDF = Tenofovir DF; 3TC = Lamivudine; EFV = Efavirenz; d4T = Stavudine; ABC = Abacavir; ZDV = Zidovudine; FPV = Fosamprenavir; RTV = Ritonavir; NFV = Nelfinavir; IND = Indinavir; FTC = Emtricitabine; ATV = Atazanavir; DRV = Darunavir; NVP = Nevirapine; RAL = Raltegravir; AZT = Azidothymidine; RPV = Rilpivirine.</p

Study design characteristics stratified by type of trial population.

*<p>Upper 95% confidence limit for Hazard ratio was no greater than 1.18; **Upper 95% confidence limit for the Hazard ratio was less than 1.40.</p

Search strategy profile of the systematic review.

<p>Search strategy profile of the systematic review.</p