Background: Clinical trials in cystic fibrosis (CF) currently use laboratory-specific reference ranges to evaluate chemistry and hematology measurements. Laboratory-specific normal reference ranges may not accurately reflect what is abnormal but clinically insignificant among CF patients.
Methods: To address this concern, data from the Phase III trial of inhaled tobramycin in CF patients was used to describe the distribution and variability of laboratory parameters. The laboratory specimens were analyzed at a central laboratory after being obtained at baseline and throughout the 24-week trial.
Results: At the time of entry into the clinical trial, 91% (463 of 508) of patients had at least a single value outside the normal range. Liver function tests (AST, ALT) were above the normal range in 16% and 12% of the patients respectively, with 2.4% of patients having an AST>2.0 times the upper limit of normal. Of the 243 patients on placebo, 242 (99.6%) had at least one laboratory parameter that changed from normal to abnormal during the 24-week follow-up period. Of those same placebo patients, 11.5% (N=28) had a laboratory parameter change from a Common Toxicity Criteria (CTC) grade 0 to grade 2 or higher during follow-up.
Conclusions: Patients with CF frequently have laboratory values outside the normal range and have significant longitudinal variability of laboratory values. Interpretation of adverse events in the clinical trial setting may be complicated by the underlying high rates of some laboratory abnormalities in the CF population. This data was presented in poster format at the American Thoracic Society International Conference, Atlanta, USA, 2002, appearing subsequently in the Conference proceedings [Goss CH, Mayer-Hamblett N, Yunker A, Waltz DA, Kronmal RA, Ramsey BW. Laboratory parameter profiles among patients with cystic fibrosis. Am J Rep Crit Care Med 2002;165(8):A283].