Whether placebo controls are methodologically indicated depends on the questions that clinical trials are designed to answer. We argued that placebos were not needed in 2 asthma trials comparing combination therapy with monotherapy and in a third trial comparing 2 dosing regimens of the same inhaled corticosteroid.1 Temple and Meyer suggest that a placebo might have been warranted to test assay sensitivity in the first 2 trials. However, both these adequately powered studies were designed to test the superiority of the combination therapy to monotherapy. Given that the component treatments in these 2 trials had previously been demonstrated to be effective, we see the potential increase in rigor from including a placebo control as having marginal scientific value. The key ethical question is whether this theoretical increment of rigor justifies the risks of asthma worsening for those randomized to placebo. Temple and Meyer suggest that use of placebo did not place study participants at undue risk, citing that in 1 of these 2 trials, those randomized to placebo did not fare significantly worse than those randomized to montelukast monotherapy. In the second trial, however, 49% of the patients receiving placebo, compared with 35% receiving salmeterol, were withdrawn from the study because of worsening asthma—a difference that was statistically significant.2 In any case, if the placebo control was not methodologically necessary for a valid trial, then there was no justification for the risk of symptom worsening experienced by the subjects in the placebo arm of these trials. By including a placebo control when it was not methodologically required, these 2 studies failed to satisfy the ethical and regulatory requirement of minimizing risk.3,4 In the case of the third study, Temple and Meyer argue that a placebo control was needed to demonstrate that the once-daily dose had efficacy. On reflection, we think that their point has merit.
Thank you for submitting a comment on this article. It will be reviewed by JAMA Internal Medicine editors. You will be notified when your comment has been published. Comments should not exceed 500 words of text and 10 references.
Do not submit personal medical questions or information that could identify a specific patient, questions about a particular case, or general inquiries to an author. Only content that has not been published, posted, or submitted elsewhere should be submitted. By submitting this Comment, you and any coauthors transfer copyright to the journal if your Comment is posted.
* = Required Field
Disclosure of Any Conflicts of Interest*
Indicate all relevant conflicts of interest of each author below, including all relevant financial interests, activities, and relationships within the past 3 years including, but not limited to, employment, affiliation, grants or funding, consultancies, honoraria or payment, speakers’ bureaus, stock ownership or options, expert testimony, royalties, donation of medical equipment, or patents planned, pending, or issued. If all authors have none, check "No potential conflicts or relevant financial interests" in the box below. Please also indicate any funding received in support of this work. The information will be posted with your response.
Some tools below are only available to our subscribers or users with an online account.
Download citation file:
Web of Science® Times Cited: 1
Customize your page view by dragging & repositioning the boxes below.
More Listings atJAMACareerCenter.com >
Enter your username and email address. We'll send you a link to reset your password.
Enter your username and email address. We'll send instructions on how to reset your password to the email address we have on record.
Athens and Shibboleth are access management services that provide single sign-on to protected resources. They replace the multiple user names and passwords necessary to access subscription-based content with a single user name and password that can be entered once per session. It operates independently of a user's location or IP address. If your institution uses Athens or Shibboleth authentication, please contact your site administrator to receive your user name and password.