title: The methodological quality of animal research in critical care: the public face of science.
abstract: BACKGROUND
  Animal research (AR) findings often do not translate to humans; one potential reason is the poor methodological quality of AR. We aimed to determine this quality of AR reported in critical care journals.
  
  
  METHODS
  All AR published from January to June 2012 in three high-impact critical care journals were reviewed. A case report form and instruction manual with clear definitions were created, based on published recommendations, including the ARRIVE guidelines. Data were analyzed with descriptive statistics.
  
  
  RESULTS
  Seventy-seven AR publications were reviewed. Our primary outcome (animal strain, sex, and weight or age described) was reported in 52 (68%; 95% confidence interval, 56% to 77%). Of the 77 publications, 47 (61%) reported randomization; of these, 3 (6%) reported allocation concealment, and 1 (2%) the randomization procedure. Of the 77 publications, 31 (40%) reported some type of blinding; of these, disease induction (2, 7%), intervention (7, 23%), and/or subjective outcomes (17, 55%) were blinded. A sample size calculation was reported in 4/77 (5%). Animal numbers were missing in the Methods section in 16 (21%) publications; when stated, the median was 32 (range 6 to 320; interquartile range, 21 to 70). Extra animals used were mentioned in the Results section in 31 (40%) publications; this number was unclear in 23 (74%), and >100 for 12 (16%). When reporting most outcomes, numbers with denominators were given in 35 (45%), with no unaccounted numbers in 24 (31%), and no animals excluded from analysis in 20 (26%). Most (49, 64%) studies reported >40, and another 19 (25%) reported 21 to 40 statistical comparisons. Internal validity limitations were discussed in 7 (9%), and external validity (to humans) discussed in 71 (92%), most with no (30, 42%) or only a vague (9, 13%) limitation to this external validity mentioned.
  
  
  CONCLUSIONS
  The reported methodological quality of AR was poor. Unless the quality of AR significantly improves, the practice may be in serious jeopardy of losing public support.
authors.affiliation: Faculty of Medicine and Dentistry, University of Alberta, Edmonton T6G 2R3, Alberta, Canada.
authors.forename: Meredith
authors.initials: M
authors.lastname: Bara
authors.affiliation: Department of Pediatrics, 4-546 Edmonton Clinic Health Academy, University of Alberta, 11405 87 Avenue, Edmonton T6G 1C9, Alberta, Canada.
authors.forename: Ari R
authors.initials: AR
authors.lastname: Joffe
keywords: Animal research; Critical care; Intensive care; Methodology
references.citation: Ann Neurol. 2011 Feb;69(2):389-99
references.pmid: 21387381
references.citation: Nat Rev Genet. 2012 Jun 18;13(7):505-16
references.pmid: 22705669
references.citation: Epidemiology. 2001 May;12(3):295-7
references.pmid: 11337600
references.citation: Am J Bioeth. 2009 Dec;9(12):62-4
references.pmid: 20013506
references.citation: Theor Biol Med Model. 2012 Sep 10;9:40
references.pmid: 22963674
references.citation: Nat Rev Neurosci. 2013 Feb;14(2):128-42
references.pmid: 23329160
references.citation: CMAJ. 2013 Mar 5;185(4):E201-11
references.pmid: 23359047
references.citation: Rev Neurosci. 2008;19(1):47-60
references.pmid: 18561820
references.citation: Ann Intern Med. 1999 Jun 15;130(12):995-1004
references.pmid: 10383371
references.citation: Exp Neurol. 2012 Feb;233(2):597-605
references.pmid: 22078756
references.citation: ILAR J. 2002;43(4):244-58
references.pmid: 12391400
references.citation: BMJ. 2012 Oct 19;345:e7101
references.pmid: 23086964
references.citation: Resuscitation. 2012 Jan;83(1):16-7
references.pmid: 22085661
references.citation: Amyotroph Lateral Scler. 2008;9(1):4-15
references.pmid: 18273714
references.citation: Nature. 2012 Mar 28;483(7391):531-3
references.pmid: 22460880
references.citation: Acad Emerg Med. 2003 Jun;10(6):684-7
references.pmid: 12782533
references.citation: Nature. 2012 Sep 6;489(7414):52-5
references.pmid: 22955614
references.citation: Crit Care Med. 2009 Jan;37(1 Suppl):S10-5
references.pmid: 19104207
references.citation: PLoS Med. 2005 Aug;2(8):e124
references.pmid: 16060722
references.citation: J Vet Intern Med. 2010 Jan-Feb;24(1):44-50
references.pmid: 19807866
references.citation: PLoS One. 2009 Nov 30;4(11):e7824
references.pmid: 19956596
references.citation: Am J Bioeth. 2009 Dec;9(12):60-1
references.pmid: 20013504
references.citation: PLoS One. 2011;6(9):e24059
references.pmid: 21915280
references.citation: Crit Care Med. 2009 Jan;37(1 Suppl):S30-7
references.pmid: 19104223
references.citation: Ann Intern Med. 1999 Jun 15;130(12):1005-13
references.pmid: 10383350
references.citation: Am J Bioeth. 2009 Dec;9(12):66-7
references.pmid: 20013508
references.citation: Am J Respir Crit Care Med. 1998 Jan;157(1):294-323
references.pmid: 9445314
references.citation: Nature. 2012 Oct 11;490(7419):187-91
references.pmid: 23060188
references.citation: Proc Natl Acad Sci U S A. 2013 Nov 26;110(48):19313-7
references.pmid: 24218581
references.citation: Lancet. 2012 Apr 21;379(9825):1551-9
references.pmid: 22516561
references.citation: Lab Anim. 2006 Jul;40(3):217-35
references.pmid: 16803640
references.citation: Nat Rev Drug Discov. 2003 Feb;2(2):151-4
references.pmid: 12563306
references.citation: Transl Stroke Res. 2013 Jun;4(3):279-85
references.pmid: 23658596
references.citation: Vet Rec. 2004 Apr 10;154(15):467-70
references.pmid: 15143737
references.citation: Ann Intern Med. 2012 Sep 18;157(6):429-38
references.pmid: 22945832
references.citation: PLoS Biol. 2010 Jun 29;8(6):e1000412
references.pmid: 20613859
references.citation: Prev Vet Med. 2009 Oct 1;91(2-4):107-15
references.pmid: 19573943
references.citation: Trends Neurosci. 2007 Sep;30(9):433-9
references.pmid: 17765332
references.citation: Nat Rev Drug Discov. 2011 Jun;10(6):428-38
references.pmid: 21629293
references.citation: Nature. 2011 Oct 19;478(7369):343-8
references.pmid: 22012392
references.citation: J Infect Dis. 2010 Jan 15;201(2):223-32
references.pmid: 20001600
references.citation: EMBO Rep. 2007 Jun;8(6):521-5
references.pmid: 17545990
references.citation: Mult Scler. 2010 Sep;16(9):1044-55
references.pmid: 20685763
references.citation: Shock. 2005 Dec;24 Suppl 1:1-6
references.pmid: 16374365
references.citation: Crit Care. 2014 Jan 14;18(1):R15
references.pmid: 24423201
references.citation: Philos Ethics Humanit Med. 2009 Jan 15;4:2
references.pmid: 19146696
references.citation: Psychol Sci. 2011 Nov;22(11):1359-66
references.pmid: 22006061
references.citation: PLoS Biol. 2013 Jul;11(7):e1001609
references.pmid: 23874156
references.citation: Nat Genet. 2007 Jun;39(6):730-2
references.pmid: 17529977
references.citation: Lab Anim. 1997 Apr;31(2):116-24
references.pmid: 9175008
references.citation: Am J Bioeth. 2009 Dec;9(12):55-9
references.pmid: 20013503
references.citation: PLoS Med. 2010 Mar 30;7(3):e1000245
references.pmid: 20361020
references.citation: Proc Natl Acad Sci U S A. 2008 May 13;105(19):6987-92
references.pmid: 18458337
references.citation: Nature. 2014 Feb 13;506(7487):150-2
references.pmid: 24522584
references.citation: Intensive Care Med. 2014 Jun;40(6):769-87
references.pmid: 24667919
references.citation: PLoS Biol. 2014 Jan;12(1):e1001756
references.pmid: 24409096
references.citation: Drug Discov Today. 2011 Aug;16(15-16):659-70
references.pmid: 21723955
references.citation: Proc Natl Acad Sci U S A. 2013 Feb 26;110(9):3507-12
references.pmid: 23401516
references.citation: EMBO Rep. 2004 Nov;5(11):1016-20
references.pmid: 15520799