Neuromuscular dose-response studies: determining sample size.
BACKGROUND
Investigators planning dose-response studies of neuromuscular blockers have rarely used a priori power analysis to determine the minimal sample size their protocols require. Institutional Review Boards and peer-reviewed journals now generally ask for this information. This study outlines a proposed method for meeting these requirements.


METHODS
The slopes of the dose-response relationships of eight neuromuscular blocking agents were determined using regression analysis. These values were substituted for γ in the Hill equation. When this is done, the coefficient of variation (COV) around the mean value of the ED₅₀ for each drug is easily calculated. Using these values, we performed an a priori one-sample two-tailed t-test of the means to determine the required sample size when the allowable error in the ED₅₀ was varied from ±10-20%.


RESULTS
The COV averaged 22% (range 15-27%). We used a COV value of 25% in determining the sample size. If the allowable error in finding the mean ED₅₀ is ±15%, a sample size of 24 is needed to achieve a power of 80%. Increasing 'accuracy' beyond this point requires increasing greater sample sizes (e.g. an 'n' of 37 for a ±12% error).


CONCLUSIONS
On the basis of the results of this retrospective analysis, a total sample size of not less than 24 subjects should be adequate for determining a neuromuscular blocking drug's clinical potency with a reasonable degree of assurance.
Department of Anesthesiology, Weill Cornell Medical College, 525 East 68th Street, New York City, NY 10065, USA. akopman@nyc.rr.com
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Kopman
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Lien
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Naguib
D000328:Adult; D004305:Dose-Response Relationship, Drug; D006801:Humans; D019148:Neuromuscular Blockade / Q000379:methods; D009466:Neuromuscular Blocking Agents / Q000008:administration & dosage* / Q000494:pharmacology; D009469:Neuromuscular Junction / Q000187:drug effects* / Q000502:physiology; D012107:Research Design; D012189:Retrospective Studies; D018401:Sample Size
D009466:Neuromuscular Blocking Agents