title: Deficient reporting and interpretation of non-inferiority randomized clinical trials in HIV patients: a systematic review.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  Systematic review.
  
  
  METHODS
  PubMed, Web of Science, and Scopus were reviewed until December 2011. Selection and extraction was performed independently by three reviewers.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors: Health Outcomes and Clinical Epidemiology Section, Department of Quantitative Health Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, United States of America.
authors: Adrian V
authors: AV
authors: Hernandez
authors: Vinay
authors: V
authors: Pasupuleti
authors: Abhishek
authors: A
authors: Deshpande
authors: Priyaleela
authors: P
authors: Thota
authors: Jaime A
authors: JA
authors: Collins
authors: Jose E
authors: JE
authors: Vidal
mesh_terms: D019380:Anti-HIV Agents / Q000627:therapeutic use*; D003627:Data Interpretation, Statistical; D016206:Databases, Bibliographic; D004334:Drug Administration Schedule; D015658:HIV Infections / Q000188:drug therapy*; D006801:Humans; D016032:Randomized Controlled Trials as Topic; D012107:Research Design; D016896:Treatment Outcome
chemical_list: D019380:Anti-HIV Agents
references: Lancet Infect Dis. 2011 Dec;11(12):907-15
references: 21933752
references: PLoS One. 2010 Oct 27;5(10):e13550
references: 21048948
references: Lancet. 2009 Sep 5;374(9692):796-806
references: 19647866
references: BMC Med Res Methodol. 2006 Sep 20;6:46
references: 16987409
references: J Acquir Immune Defic Syndr. 2010 Mar;53(3):323-32
references: 20032785
references: Curr Med Res Opin. 2004 Jul;20(7):1103-14
references: 15265255
references: J Antimicrob Chemother. 2009 Jul;64(1):126-34
references: 19403652
references: JAMA. 2006 Mar 8;295(10):1152-60
references: 16522836
references: JAMA. 2010 May 26;303(20):2058-64
references: 20501928
references: J Antimicrob Chemother. 2011 Aug;66(8):1878-85
references: 21652619
references: Clin Infect Dis. 2004 Oct 1;39(7):1038-46
references: 15472858
references: Lancet. 2010 Jan 30;375(9712):396-407
references: 20074791
references: Lancet. 2007 Jul 7;370(9581):49-58
references: 17617272
references: Int J STD AIDS. 2010 Mar;21(3):166-71
references: 20215619
references: AIDS Res Ther. 2009 Apr 09;6:3
references: 19358725
references: J Clin Epidemiol. 2007 Mar;60(3):241-9
references: 17292017
references: Antivir Ther. 2011;16(5):759-69
references: 21817198
references: PLoS One. 2011;6(9):e22871
references: 21915255
references: PLoS One. 2011;6(6):e21450
references: 21738668
references: Lancet. 2011 Jul 16;378(9787):229-37
references: 21763935
references: PLoS One. 2010 Apr 22;5(4):e10307
references: 20442758
references: Lancet. 2006 Aug 5;368(9534):476-82
references: 16890834
references: J Acquir Immune Defic Syndr. 2010 Jun;54(2):143-51
references: 20134330
references: AIDS. 2000 Apr 14;14(6):671-81
references: 10807190
references: AIDS. 2010 Sep 24;24(15):2365-74
references: 20802297
references: Med J Aust. 2006 Sep 4;185(5):263-7
references: 16948622
references: BMJ. 2002 Aug 3;325(7358):249
references: 12153921
references: J Antimicrob Chemother. 2010 Nov;65(11):2436-44
references: 20843990
references: JAMA. 2006 Mar 8;295(10):1147-51
references: 16522835
references: Lancet. 2008 Aug 23;372(9639):646-55
references: 18722869
references: AIDS. 2008 Jul 31;22(12):1389-97
references: 18614861
references: J Acquir Immune Defic Syndr. 2006 Oct 1;43(2):153-60
references: 16951643
references: J Acquir Immune Defic Syndr. 2010 Apr;53(5):582-8
references: 20090545
references: AIDS. 2008 May 11;22(8):913-21
references: 18453850
references: JAMA. 2006 Mar 8;295(10):1172-4
references: 16522840
references: JAMA. 2004 Jul 14;292(2):191-201
references: 15249568
references: AIDS. 2008 Jan 11;22(2):F1-9
references: 18097218
references: Lancet. 2010 Jul 3;376(9734):33-40
references: 20557927
references: AIDS. 2004 Jul 23;18(11):1529-37
references: 15238771
references: AIDS. 2009 Jan 14;23(2):203-12
references: 19098490
references: J Antimicrob Chemother. 2009 Feb;63(2):380-8
references: 19036752
references: AIDS. 2007 Feb 19;21(4):457-66
references: 17301564
references: Antivir Ther. 2011;16(3):339-48
references: 21555816
references: J Acquir Immune Defic Syndr. 2006 Dec 15;43(5):535-40
references: 17057609
references: Lancet. 2010 Jan 9;375(9709):123-31
references: 20004464
references: Clin Infect Dis. 2009 Oct 15;49(8):1259-67
references: 19757993
references: Lancet. 2011 Jul 16;378(9787):238-46
references: 21763936
references: Lancet Infect Dis. 2011 Nov;11(11):825-33
references: 21831714
references: Ann Intern Med. 2006 Jul 4;145(1):62-9
references: 16818930
references: AIDS. 2004 Nov 19;18(17):2269-76
references: 15577539
references: J Acquir Immune Defic Syndr. 2005 Apr 1;38(4):417-25
references: 15764958
references: BMC Infect Dis. 2003 Jun 10;3:10
references: 12795812
references: AIDS. 2010 Jan 16;24(2):223-30
references: 20010070
references: AIDS. 2010 Jul 17;24(11):1697-707
references: 20467288