1 Det Nordiske Cochrane Center, Cochranecenteret Rigshospitalet, Rigshospitalet, The Capital Region of Denmark2 Department of Biochemistry, Neurobiology and Ageing Programme, Centre for Life Sciences (CeLS), National University of Singapore, 28 Medical Drive, #04-21 Lab 2, 117456, Singapore.3 Department of Pathology, University of Oklahoma Health Sciences Center 940, Stanton L. Young Blvd., BMSB 451, Oklahoma City, Oklahoma 73104, USA.4 Department of Pediatrics, Division of Neonatology, J.W. Goethe - University Hospital Theodor Stern Kai 7, 60590, Frankfurt, Germany.
OBJECTIVES: To examine the impact of not blinding outcome assessors on estimates of intervention effects in animal experiments modeling human clinical conditions. STUDY DESIGN AND SETTING: We searched PubMed, Biosis, Google Scholar, and HighWire Press and included animal model experiments with both blinded and nonblinded outcome assessors. For each experiment, we calculated the ratio of odds ratios (ROR), that is, the odds ratio (OR) from nonblinded assessments relative to the corresponding OR from blinded assessments. We standardized the ORs according to the experimental hypothesis, such that an ROR <1 indicates that nonblinded assessor exaggerated intervention effect, that is, exaggerated benefit in experiments investigating possible benefit or exaggerated harm in experiments investigating possible harm. We pooled RORs with inverse variance random-effects meta-analysis. RESULTS: We included 10 (2,450 animals) experiments in the main meta-analysis. Outcomes were subjective in most experiments. The pooled ROR was 0.41 (95% confidence interval [CI], 0.20, 0.82; I(2) = 75%; P < 0.001), indicating an average exaggeration of the nonblinded ORs by 59%. The heterogeneity was quantitative and caused by three pesticides experiments with very large observer bias, pooled ROR was 0.20 (95% CI, 0.07, 0.59) in contrast to the pooled ROR in the other seven experiments, 0.82 (95% CI, 0.57, 1.17). CONCLUSION: Lack of blinding of outcome assessors in animal model experiments with subjective outcomes implies a considerable risk of observer bias.
Journal of Clinical Epidemiology, 2014, Vol 67, Issue 9, p. 973-83