Letters Section Editor: Robert M. Golub,
MD, Senior Editor.
To the Editor: Dr Pluta and colleagues found
a significant benefit from the use of sodium nitrite in preventing delayed
vasospasm following subarachnoid hemorrhage in a study of 14 monkeys.1 We are concerned about these conclusions given certain
aspects of the study design.
Animal models allow well-controlled evaluation of new therapies prior
to definitive studies in humans. However, these models do not eliminate the
potential biases that are well-described in human studies. Human trials use
random treatment allocation to distribute the variability among patients evenly
between treatment groups.2 While the biological
variation among subjects may be less in animal models than in human populations,
genetic equivalence cannot be assumed, and there may be significant differences
between treatment groups.3 While this study
is strengthened by blinded outcome assessment, the 2 treatment groups may
still have differed with respect to important baseline and prognostic covariates.
Furthermore, the treating investigators were not blinded to treatment status
during the intervention, which may have resulted in differential management
of the groups. Human clinical trials that do not use randomization and blinding
have been shown to overestimate the magnitude of treatment effects.4 Indeed, a human study of a therapy that did not utilize
these rigorous methods would likely be viewed skeptically by clinicians.
Heard K, Bebarta VS, Lowenstein SR. Methodological Standards in Human vs Animal Clinical Trials. JAMA. 2005;294(1):40-41. doi:10.1001/jama.294.1.40-a