Article type
Year
Abstract
Background:
Translational medicine relies substantially on animal model experiments. Such experiments rarely implement blinded outcome assessors, in contrast to the frequent use of blinded outcome assessors in human clinical trials.
Objectives:
To examine the impact of not blinding outcome assessors on estimates of intervention effects in animal experiments modelling human clinical conditions.
Methods:
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) i.e. 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 a ROR < 1 indicated that nonblinded assessors exaggerated intervention effects i.e. 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 (2450 animals) experiments in the main meta-analysis. Outcomes were subjective in most experiments. The pooled ROR was 0.41 (95% confidence interval 0.20 to 0.82; I2 = 75%, P value < 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 0.20 (0.07 to 0.59) in contrast to the pooled ROR in the other seven experiments, 0.82 (0.57 to 1.17).
Conclusions:
Lack of blinding of outcome assessors in animal model experiments with subjective outcomes implies a considerable risk of observer bias.
Translational medicine relies substantially on animal model experiments. Such experiments rarely implement blinded outcome assessors, in contrast to the frequent use of blinded outcome assessors in human clinical trials.
Objectives:
To examine the impact of not blinding outcome assessors on estimates of intervention effects in animal experiments modelling human clinical conditions.
Methods:
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) i.e. 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 a ROR < 1 indicated that nonblinded assessors exaggerated intervention effects i.e. 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 (2450 animals) experiments in the main meta-analysis. Outcomes were subjective in most experiments. The pooled ROR was 0.41 (95% confidence interval 0.20 to 0.82; I2 = 75%, P value < 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 0.20 (0.07 to 0.59) in contrast to the pooled ROR in the other seven experiments, 0.82 (0.57 to 1.17).
Conclusions:
Lack of blinding of outcome assessors in animal model experiments with subjective outcomes implies a considerable risk of observer bias.