A 2016 study in New England Journal of Medicine has received
a substantial correction, which affected several aspects of the article.
Typically, an error that affects so much of a paper would
undermine the results (and possibly lead to a retraction). But in this case,
the revised dose calculations actually strengthened the findings, according to
the first author.
The NEJM study aimed to clarify whether patients with a
neuromuscular disease called myasthenia gravis benefit from a surgical
procedure to remove the thymus. About half of the patients received surgery
plus the steroid prednisone, while the rest only received the steroid. The researchers
found patients who received the surgery fared better.
Shortly after the paper was published in August 2016, the
authors discovered an error in the calculation of the average prednisone dose.
According to Gil Wolfe, the first author of the paper, when the researchers
corrected the error:
“The recalculation didn’t reverse any of the findings; it
actually strengthened them, making thymectomy look even better.”
In other words, people who had surgery needed less
prednisone overall, and the authors found the doses went down faster in the
surgery group than they initially thought.
Here’s the correction notice for “Randomized Trial of
Thymectomy in Myasthenia Gravis,” which explains the calculation error:
“Randomized Trial of Thymectomy in Myasthenia Gravis
(Original Article, N Engl J Med 2016;375:511-522). An error in calculating the
time-weighted average of the doses of prednisone led to incorrect point
estimates for the primary and secondary outcomes. For patients whose prednisone
dose was tapered and then stopped before month 36 and who remained off
prednisone, the time-weighted dose calculations did not account for the months
during which the patients were not receiving the medication. As a result, the
time-weighted prednisone doses for such patients were overestimated. The errors
affected several parts of the article: the Abstract, the Results section, the
Discussion, Figure 1B, and Table 2. The Supplementary Appendix was also
affected. The direction of change of the primary and secondary outcomes and the
overall conclusions of the trial are not altered from the original published
version. The article is correct at NEJM.org.”
Wolfe, professor and chair of the Department of Neurology at
the University at Buffalo School of Medicine and Biomedical Sciences, the State
University of New York, told us:
“We wanted prednisone data for the full 36 months patients
were followed. But for patients who went down to 0 mg of the drug during the
study, the time-weighted dose calculation stopped before 36 months.”
Wolfe explained that when the authors recalculated the drug
dose over the three year study period, the revised numbers made the surgery
option look even better than the original numbers had.
Wolfe said that the recalculation only affected the
prednisone dose data, not the data on disease severity, patient quality of
life, or complications from surgery or prednisone.
A spokesperson for NEJM told us the journal never considered
a retraction:
“In the process of looking at the computer program that did
the analysis for this trial, the study statisticians found that that the amount
of prednisone was miscounted. They reviewed the published article and found
that they needed to make changes in dose reported for each group.”
http://retractionwatch.com/2017/06/20/big-corrections-usually-weaken-findings-recent-nejm-one-strengthened-author-says/
Courtesy of Doximity
Courtesy of a colleague
No comments:
Post a Comment