In Reply Kleinman and Ostacher have indicated concern about the choice of end points for our recent clinical trial of gabapentin in those with alcohol use disorder (AUD).1 One concern was the use of the percentage of disialo carbohydrate-deficient transferrin (%dCDT) biomarker of heavy drinking to adjust the verbal reports of drinking provided during the trial, a procedure not detailed a priori. Unfamiliarity with this biomarker of alcohol consumption might underlie some of this concern. In fact, when assayed by the International Federation of Clinical Chemistry–recommended high-performance liquid chromatography assay,2 a %dCDT value above 1.7% has almost 100% specificity for heavy alcohol consumption, and, by extension, any alcohol consumption. Prior to knowing the participant study-drug assignments and based on their having positive %dCDT values above 1.7% during the trial, we judged that several participants had misreported their drinking status, not an unusual occurrence in both clinical trials and practice. We had to make a choice regarding which bias was more acceptable: to just report the verbally reported drinking in these cases, which we judged to be erroneous, or to adjust their treatment outcome to a heavy-drinking and/or nonabstinent status. While we judged the latter to be more valid, we also reported the nonadjusted verbally reported drinking status as well, thereby allowing readers to draw their own conclusions. All analyses on both the adjusted and the nonadjusted drinking outcomes were done prior to breaking the blind on study medication assignments. Of note, in another recent clinical trial by our group,3 we had reported that %dCDT values provided equal, or better, treatment effect sizes compared with verbally reported drinking status, attesting to its value as an important biomarker to consider in judging efficacy in alcohol clinical trials.
Identify all potential conflicts of interest that might be relevant to your comment.
Conflicts of interest comprise financial interests, activities, and relationships within the past 3 years including but not limited to employment, affiliation, grants or funding, consultancies, honoraria or payment, speaker's bureaus, stock ownership or options, expert testimony, royalties, donation of medical equipment, or patents planned, pending, or issued.
Err on the side of full disclosure.
If you have no conflicts of interest, check "No potential conflicts of interest" in the box below. The information will be posted with your response.
Not all submitted comments are published. Please see our commenting policy for details.
Anton RF, Hoffman M. Changed Primary Outcome Between Trial Registration and Publication—Reply. JAMA Intern Med. Published online July 13, 2020. doi:10.1001/jamainternmed.2020.2173
Customize your JAMA Network experience by selecting one or more topics from the list below.
Create a personal account or sign in to: