Chapter 4. Drug Literature Evaluation I: Controlled Clinical Trial Evaluation
Read the excerpt of the following clinical trial summary and answer the questions that follow.
A study was conducted to assess the ability of low-dose erythromycin to reduce pulmonary exacerbation in persons with frequent noncystic fibrosis (CF) bronchiectasis. Study subjects were assigned to either erythromycin 250 mg twice daily (n = 59) or placebo (n = 58); baseline demographics were factored into randomizing the subjects to the groups. Both the erythromycin and placebo tablets were similar in appearance, taste, and shape; no one knew who was in which group. Subjects were between the ages of 20 and 85 years and had to have two pulmonary exacerbations requiring systemic antibiotic treatment within the prior 12 months, daily sputum production, but stable for at least 4 weeks. Exclusion criteria included those with CF and changes in any maintenance medications in the 4 weeks prior to study entry. The primary endpoint was the mean rate of protocol-defined pulmonary exacerbations (PDPE) per patient per year (defined as subject requiring antibiotic therapy for more than 24 hours, increased sputum production, and deterioration of symptoms). The results for all subjects randomized into this study were included in the final analysis regardless of whether they completed the entire study duration (48 weeks). Other endpoints included FEV1, change in exercise capacity, and adverse side effects. Tablet counts were used to determine adherence. Subjects returned to the clinic for follow-up 11 times over 48 weeks. Subjects also had access to contact an investigator any time of the day to report exacerbation symptoms. The investigators calculated that a total 118 subjects were needed to be enrolled in the study to have 90% ability to detect a difference between the erythromycin and placebo group for the primary endpoint. A p-value less than 0.05 was considered significant.
Baseline demographics were similar between the two groups in terms of average age (62 years), gender (60% female), and exacerbations per year. A total of 107 subjects completed the entire study duration and medication adherence was approximately 96%. Less incidences of PDPE were reported in the erythromycin group versus placebo (76 versus 114 episodes, respectively; p = 0.003). The mean PDPE was 1.29 versus 1.97 per patient per year. Less of a decrease in FEV1 (p = 0.04) and better exercise capacity (p = 0.4) was measured with erythromycin compared to placebo. Few side effects occurred in both groups. The investigators concluded that erythromycin did provide beneficial effects versus placebo in these subjects.
Which of the following is a false statement regarding this trial?
a. Randomization reduces bias in selecting subjects to the groups.
b. Statistical tests are validated with randomization being included in the trial.