If a treatment for asthma makes an asthma patient feel better, did it work? It’s hard to say, according to an article by Wechsler et al published this week in NEJM. The authors report the results of a randomized double-blind crossover pilot study comparing the effectiveness of four interventions: an active albuterol inhaler, a placebo inhaler, sham acupuncture, and “no treatment.”
The study assigned 39 stable asthmatics to receive each of the four interventions on three separate occasions, for a total of 12 treatment visits over the course of a year. At each visit, patients were asked to rate their degree of symptomatic improvement after receiving the intervention. Spirometry was also performed to assess the maximum forced expiratory volume in the first second (FEV1), a commonly used indicator of lung function.
The authors found that patients’ own evaluations of intervention effectiveness differed considerably from the objective spirometry results. Patients reported statistically significant symptomatic improvement with all three treatment-based interventions – albuterol (50%), placebo albuterol (45%), and sham acupuncture (46%) – as compared with the “no treatment” control (21%). Moreover, there was no statistically significant difference in the degree of relief provided by the active albuterol versus the placebo inhaler.
By objective measures, however, only the active albuterol was effective in improving lung function. Patients experienced an average improvement in FEV1 of 20.1% with the blinded albuterol; this was consistent with the 21.9% average improvement in response to open-label albuterol seen at the time of screening for the study. In contrast, the mean FEV1 improvement was only 7.5% with the placebo albuterol, 7.3% with sham acupuncture, and 7.1% with the “no treatment” control. This suggested a statistically significant difference in lung function following treatment with albuterol versus placebo.
In an accompanying editorial, Daniel E. Moerman, Ph.D., of the University of Michigan-Dearborn discusses the implications of these findings. “That [the patients] felt improved even when their FEV1 had not increased,” he writes, “begs the question of what is the more important outcome in medicine, the objective or the subjective, the doctor’s or the patients’ perception?”
The authors put it another way: “The bifurcation of placebo effects between objective and subjective outcomes found in this pilot study may represent the distinction that social scientists make between treating disease (objective physiology) and treating illness (subjective perceptions). While effective medications target and modulate objective biology, the mere ritual of treatment may impact patients’ self-monitoring, and perceptions of subjective aspects of their disease.”
NEJM editor-in-chief Jeffrey M. Drazen, M.D., said that these data raise questions about what outcomes should be measured in clinical asthma studies. While most studies are set-up to determine if there is an objective improvement in airflow, patient centered outcomes should also be considered as important.
What degree of importance do you assign to subjective versus objective measures when treating patients with asthma? Will the results of this study influence your clinical practice?