Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
BMC Medical Research Methodology
Published in: BMC Medical Research Methodology 1/2014

Open Access 01-12-2014 | Research article

SYRCLE’s risk of bias tool for animal studies

Authors: Carlijn R Hooijmans, Maroeska M Rovers, Rob BM de Vries, Marlies Leenaars, Merel Ritskes-Hoitinga, Miranda W Langendam

Published in: BMC Medical Research Methodology | Issue 1/2014

Login to get access

Abstract

Background

Systematic Reviews (SRs) of experimental animal studies are not yet common practice, but awareness of the merits of conducting such SRs is steadily increasing. As animal intervention studies differ from randomized clinical trials (RCT) in many aspects, the methodology for SRs of clinical trials needs to be adapted and optimized for animal intervention studies. The Cochrane Collaboration developed a Risk of Bias (RoB) tool to establish consistency and avoid discrepancies in assessing the methodological quality of RCTs. A similar initiative is warranted in the field of animal experimentation.

Methods

We provide an RoB tool for animal intervention studies (SYRCLE’s RoB tool). This tool is based on the Cochrane RoB tool and has been adjusted for aspects of bias that play a specific role in animal intervention studies. To enhance transparency and applicability, we formulated signalling questions to facilitate judgment.

Results

The resulting RoB tool for animal studies contains 10 entries. These entries are related to selection bias, performance bias, detection bias, attrition bias, reporting bias and other biases. Half these items are in agreement with the items in the Cochrane RoB tool. Most of the variations between the two tools are due to differences in design between RCTs and animal studies. Shortcomings in, or unfamiliarity with, specific aspects of experimental design of animal studies compared to clinical studies also play a role.

Conclusions

SYRCLE’s RoB tool is an adapted version of the Cochrane RoB tool. Widespread adoption and implementation of this tool will facilitate and improve critical appraisal of evidence from animal studies. This may subsequently enhance the efficiency of translating animal research into clinical practice and increase awareness of the necessity of improving the methodological quality of animal studies.
Appendix
Available only for authorised users
Literature
1.
Sandercock P, Roberts I: Systematic reviews of animal experiments. Lancet. 2002, 360 (9333): 586-10.1016/S0140-6736(02)09812-4.CrossRefPubMed
2.
Hooijmans CR, Rovers M, de Vries RB, Leenaars M, Ritskes-Hoitinga M: An initiative to facilitate well-informed decision-making in laboratory animal research: report of the First International Symposium on Systematic Reviews in Laboratory Animal Science. Lab Anim. 2012, 46 (4): 356-357. 10.1258/la.2012.012052.CrossRefPubMed
3.
Muhlhausler BS, Bloomfield FH, Gillman MW: Whole animal experiments should be more like human randomized controlled trials. PLoS Biol. 2013, 11 (2): e1001481-10.1371/journal.pbio.1001481.CrossRefPubMedPubMedCentral
4.
Chalmers TC, Celano P, Sacks HS, Smith H: Bias in treatment assignment in controlled clinical trials. N Engl J Med. 1983, 309 (22): 1358-1361. 10.1056/NEJM198312013092204.CrossRefPubMed
5.
Macleod MR, Fisher M, O’Collins V, Sena ES, Dirnagl U, Bath PM, Buchan A, van der Worp HB, Traystman R, Minematsu K, Donnan GA, Howells DW: Good laboratory practice: preventing introduction of bias at the bench. Stroke. 2009, 40 (3): e50-e52. 10.1161/STROKEAHA.108.525386.CrossRefPubMed
6.
Moher D, Cook DJ, Jadad AR, Tugwell P, Moher M, Jones A, Pham B, Klassen TP: Assessing the quality of reports of randomised trials: implications for the conduct of meta-analyses. Health Technol Assess. 1999, 3 (12): 1-4. 1–98
7.
Schulz KF, Chalmers I, Hayes RJ, Altman DG: Empirical evidence of bias. Dimensions of methodological quality associated with estimates of treatment effects in controlled trials. JAMA. 1995, 273 (5): 408-412. 10.1001/jama.1995.03520290060030.CrossRefPubMed
8.
Cochrane Handbook for Systematic Reviews of Interventions. Edited by: Higgins JPT, Green S. 2008, Chichester: John Wiley & Sons
9.
Higgins JP, Altman DG, Gotzsche PC, Juni P, Moher D, Oxman AD, Savovic J, Schulz KF, Weeks L, Sterne JA, Cochrane Bias Methods Group, Cochrane Statistical Methods Group: The Cochrane Collaboration’s tool for assessing risk of bias in randomised trials. BMJ. 2011, 343: d5928-10.1136/bmj.d5928.CrossRefPubMedPubMedCentral
10.
Hooijmans CR, Pasker-de Jong PC, de Vries RB, Ritskes-Hoitinga M: The effects of long-term omega-3 fatty acid supplementation on cognition and Alzheimer’s pathology in animal models of Alzheimer’s disease: a systematic review and meta-analysis. J Alzheimers Dis. 2012, 28 (1): 191-209.PubMed
11.
Krauth D, Woodruff TJ, Bero L: Instruments for assessing risk of bias and other methodological criteria of published animal studies: a systematic review. Environ Health Perspect. 2013, 121: 985-992.PubMedPubMedCentral
12.
Sena E, van der Worp HB, Howells D, Macleod M: How can we improve the pre-clinical development of drugs for stroke?. Trends Neurosci. 2007, 30 (9): 433-439. 10.1016/j.tins.2007.06.009.CrossRefPubMed
13.
Wever KE, Menting TP, Rovers M, van der Vliet JA, Rongen GA, Masereeuw R, Ritskes-Hoitinga M, Hooijmans CR, Warle M: Ischemic preconditioning in the animal kidney, a systematic review and meta-analysis. PLoS One. 2012, 7 (2): e32296-10.1371/journal.pone.0032296.CrossRefPubMedPubMedCentral
14.
Thayer K, Rooney A, Boyles A, Holmgren S, Walker V, Kissling G: Draft protocol for systematic review to evaluate the evidence for an association between bisphenol A (BPA) exposure and obesity. National Toxicology Program. 2013, U.S. Department of health and human services
15.
Whiting PF, Rutjes AW, Westwood ME, Mallett S, Deeks JJ, Reitsma JB, Leeflang MM, Sterne JA, Bossuyt PM, Group Q: QUADAS-2: a revised tool for the quality assessment of diagnostic accuracy studies. Ann Intern Med. 2011, 155 (8): 529-536. 10.7326/0003-4819-155-8-201110180-00009.CrossRefPubMed
16.
Whiting P, Rutjes AW, Reitsma JB, Bossuyt PM, Kleijnen J: The development of QUADAS: a tool for the quality assessment of studies of diagnostic accuracy included in systematic reviews. BMC Med Res Methodol. 2003, 3: 25-10.1186/1471-2288-3-25.CrossRefPubMedPubMedCentral
17.
Kilkenny C, Parsons N, Kadyszewski E, Festing MF, Cuthill IC, Fry D, Hutton J, Altman DG: Survey of the quality of experimental design, statistical analysis and reporting of research using animals. PLoS One. 2009, 4 (11): e7824-10.1371/journal.pone.0007824.CrossRefPubMedPubMedCentral
18.
Beynen ACG,K, van Zutphen LFM: Standardization of the animal and itsenvironment. In Principles of Laboratory Animal Science, Revised Edition.Edited by van Zutphen LFMB V, Beynen AC. Amsterdam and New York:Elsevier B.V.; 2001
19.
Perel P, Roberts I, Sena E, Wheble P, Briscoe C, Sandercock P, Macleod M, Mignini LE, Jayaram P, Khan KS: Comparison of treatment effects between animal experiments and clinical trials: systematic review. BMJ. 2007, 334 (7586): 197-10.1136/bmj.39048.407928.BE.CrossRefPubMed
20.
Roberts I, Kwan I, Evans P, Haig S: Does animal experimentation inform human healthcare? Observations from a systematic review of international animal experiments on fluid resuscitation. BMJ. 2002, 324 (7335): 474-476. 10.1136/bmj.324.7335.474.CrossRefPubMedPubMedCentral
21.
Faggion CM, Giannakopoulos NN, Listl S: Risk of bias of animal studies on regenerative procedures for periodontal and peri-implant bone defects - a systematic review. J Clin Periodontol. 2011, 38 (12): 1154-1160. 10.1111/j.1600-051X.2011.01783.x.CrossRefPubMed
22.
Hooijmans CR, de Vries RB, Rovers MM, Gooszen HG, Ritskes-Hoitinga M: The effects of probiotic supplementation on experimental acute pancreatitis: a systematic review and meta-analysis. PLoS One. 2012, 7 (11): e48811-10.1371/journal.pone.0048811.CrossRefPubMedPubMedCentral
23.
Hooijmans CR, Leenaars M, Ritskes-Hoitinga M: A gold standard publication checklist to improve the quality of animal studies, to fully integrate the Three Rs, and to make systematic reviews more feasible. Altern Lab Anim. 2010, 38 (2): 167-182.PubMed
24.
Kilkenny C, Browne WJ, Cuthill IC, Emerson M, Altman DG: Improving bioscience research reporting: the ARRIVE guidelines for reporting animal research. PLoS Biol. 2010, 8 (6): e1000412-10.1371/journal.pbio.1000412.CrossRefPubMedPubMedCentral
25.
Begg C, Cho M, Eastwood S, Horton R, Moher D, Olkin I, Pitkin R, Rennie D, Schulz KF, Simel D, Stroup DF: Improving the quality of reporting of randomized controlled trials. The CONSORT statement. JAMA. 1996, 276 (8): 637-639. 10.1001/jama.1996.03540080059030.CrossRefPubMed
26.
Moher D, Liberati A, Tetzlaff J, Altman DG: Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med. 2009, 6 (7): e1000097-10.1371/journal.pmed.1000097.CrossRefPubMedPubMedCentral
27.
Johnston NA, Nevalainen T: Impact of biotic and abiotic environment on animal experiments. Handbook of Laboratory Animal Science (Book 1). Edited by: Hau JS S. 2010, Boca Raton, Florida: CRC Press, 343-369. 3
28.
Kemppinen N, Meller A, Bjork E, Kohila T, Nevalainen T: Exposure in the shoebox: comparison of physical environment of ivcs and open rat cages. Scand J Lab Anim Sci. 2008, 35 (2): 97-103.
29.
Donnelly H, Saibaba P: Light-intensity and the estrous-cycle in albino and normally pigmented mice. Lab Anim. 1993, 27 (4): 385-390. 10.1258/002367793780745598.CrossRefPubMed
30.
Vanderschuren LJMJ, Niesink RJM, Spruijt BM, Vanree JM: Influence of environmental-factors on social play-behavior of juvenile rats. Physiol Behav. 1995, 58 (1): 119-123. 10.1016/0031-9384(94)00385-I.CrossRefPubMed
31.
Clough G: Environmental-effects on animals used in biomedical-research. Biol Rev. 1982, 57 (Aug): 487-523.CrossRefPubMed
32.
Clough G: Environmental factors in relation to the comfort and well-being of laboratory rats and mice. Standards in Laboratory Animal Management. 1984, Wheathampstead: Universities Federation for Animal Welfare (UFAW), 1: 7-24.
33.
Harri MNE: Effect of body-temperature on cardiotoxicity of isoprenaline in rats. Acta Pharmacol Toxicol (Copenh). 1976, 39 (2): 214-224.CrossRef
34.
Bruguerolle B: Circadian changes in pharmacokinetics. Therapie. 1983, 38 (3): 223-235.PubMed
35.
Bruguerolle B, Valli M, Bouyard L, Jadot G, Bouyard P: Effect of the hour of administration on the pharmacokinetics of lidocaine in the rat. Eur J Drug Metab Pharmacokinet. 1983, 8 (3): 233-238. 10.1007/BF03188753.CrossRefPubMed
36.
Marrino P, Gavish D, Shafrir E, Eisenberg S: Diurnal-variations of plasma-lipids, tissue and plasma-lipoprotein lipase, and VLDL secretion rates in the rat - a model for studies of VLDL metabolism. Biochim Biophys Acta. 1987, 920 (3): 277-284. 10.1016/0005-2760(87)90105-6.CrossRefPubMed
37.
Claassen V: Circadian and other rhytms. Neglected Factors in Pharmacology and Neuroscience Research Volume 12. Edited by: Huston JP. 1994, Amsterdam and New York: Elsevier Science B.V, 243-381.
38.
Claassen V: Housing conditions. Neglected Factors in Pharmacology and Neuroscience Research, Volume 12. Edited by: Huston JP. 1994, Amsterdam and New York: Elsevier Science B.V, 223-250.
Metadata
Title
SYRCLE’s risk of bias tool for animal studies
Authors
Carlijn R Hooijmans
Maroeska M Rovers
Rob BM de Vries
Marlies Leenaars
Merel Ritskes-Hoitinga
Miranda W Langendam
Publication date
01-12-2014
Publisher
BioMed Central
Published in
BMC Medical Research Methodology / Issue 1/2014
Electronic ISSN: 1471-2288
DOI
https://doi.org/10.1186/1471-2288-14-43

Other articles of this Issue 1/2014

BMC Medical Research Methodology 1/2014 Go to the issue

Research article

Comparing classification methods for diffuse reflectance spectra to improve tissue specific laser surgery

Research article

Reducing decision errors in the paired comparison of the diagnostic accuracy of screening tests with Gaussian outcomes

Research article

Presenting simulation results in a nested loop plot

Correspondence

Three steps to writing adaptive study protocols in the early phase clinical development of new medicines

Research article

Measuring health-related quality of life in chronic obstructive pulmonary disease: properties of the EQ-5D-5L and PROMIS-43 short form

Research article

Comparison of intervention effects in split-mouth and parallel-arm randomized controlled trials: a meta-epidemiological study