Ethical dilemmas in a randomized trial of asthma treatment: Can Bayesian statistical analysis explain the results?

Objectives: The original objective was to determine whether the use of bile vel positive airway pressure (BiPAP) ventilation would reduce the need for endotracheal intubation, the length of hospital stay, and hospital charges in patients with status asthmaticus. The development of physician treatment bias made patient enrollment difficult. The article subsequently describes the use of Bayesian statistics to explain study results when this bias occ urs. Methods: This study was a prospective, randomized controlled clinical trial conducted over a 34.5-month period at an urban university hospital wi th an emergency department census of 94,000 annual visits. Patients remaini ng in status asthmaticus after initial standard treatment with inhaled beta -agonists and steroids were randomized to receive BiPAP ventilation plus st andard treatment versus standard treatment alone (non-BiPAP), with intubati on for either group as needed. Patients with concurrent cardiac or other pu lmonary diseases were excluded. The primary outcome measures were endotrach eal intubation rate and length of hospital stay. Secondary outcome measures included vital signs (respiratory rate, pulse rate, blood pressure), chang es in expiratory peak flow, changes in pulse oximetry values, and hospital charges. Data were analyzed using Fisher's exact test, Mann-Whitney tests, and Bayesian statistics. For patients enrolled in the study more than once, data analysis was performed on the first enrollment only. Results: Ninetee n patients were enrolled in the BiPAP group and 16 patients in the non-BiPA P group. Patients were frequently enrolled more than once and the data from the subsequent enrollments were excluded from the analysis. A marked decre ase in enrollment, due to physician treatment bias, led to a premature term ination of the study. Demographics showed that the groups were similar in a ge, sex, initial peak flow rate, and arterial blood gas measurements. There was a 7.3% increase (95% CI = -22 to +45) in the intubation rate in the no n-BiPAP group (n = 2) compared with that for the BiPAP group (n = 1). No si gnificant difference was seen in length of hospital stay or hospital charge s, although there was a favorable trend toward the BiPAP group. Complicatio ns encountered in the BiPAP group included one patient with discomfort asso ciated with the nasal BiPAP mask. Bayesian analysis demonstrated that in or der for the collected data to be convincing at the 95% confidence level, th e prior conviction among treating physicians that BiPAP was a successful tr eatment modality would have had to be 98.9%. Conclusions: In this study, Bi PAP appeared to have no deleterious effects in patients with status asthmat icus, with a trend toward decreased endotracheal intubation rate, decreased length of hospital stay, and decreased hospital charges. Although further study with more patients is needed to determine the clinical and statistica l significance of this intervention, ethical concerns regarding withholding BiPAP treatment from the patients in the control group forced a premature termination of the study in the authors' institution.