This paper appeared in Lancet online publication April 25th, 2019.
I have done a 'review of a review'. The 'A Leickly Story' website has many articles that I have reviewed and critiqued. During my time as a graduate student in Pharmacology, I learned the steps needed to critically review articles. Since my pre-medical school days, I continue to use those valuable tools. Hopefully, this review may provide a few more questions and a perspective on this important topic, especially as peanut OIT becomes more popular.
This article was of particular interest to me. However, very difficult to review. Many of the references needed to be checked and since this was a systematic review and meta-analyses- the formulas used to analyze the data are problematic and elusive. The reader should be able to look at the data and recreate what was in the paper.
My review focused on the concern with the conclusions about anaphylaxis with peanut oral immunotherapy. Specifically the conclusions that were reached regarding anaphylaxis and the warnings. I will share an overall impression and look at the two articles that were driving the conclusions on the anaphylaxis risk. The more intense review can be found on Goggle Drive- Review of the Lancet article on Peanut Oral Immunotherapy.
Please click on the link for the full review-journal club style.
My conclusions-
- Not a carefully written paper. There were many errors with dates of references, the names of the authors, interpretation, and use of the data from the references.
- Two studies accounted for two-thirds of the weight for the analysis. One of the studies was from a company website. That study had 22/23 subjects experiencing anaphylaxis. This study was not critically reviewed. How could a safety and monitoring board allow the continuation of a study with such a high frequency of anaphylaxis?
- Numbers in the paper do not match internally (from tables to figures) or externally from references to the analysis presented.
- There clearly were more episodes of anaphylaxis, however there were a large number of opportunities to experience reactions.
The PALISADES report that was recently in the New England Journal of Medicine is readily available for looking at a few numbers. There were 413 who entered the treatment arm of the study- they got peanut OIT-active agent. Upon entry, 72% or 297 of the OIT group were known to have had anaphylaxis with peanut exposure in their past. Now they are given peanut protein. Below are the number of expected reactions related to a potential reaction rate. If a repeat reaction with anaphylaxis happens 100% of the time, the study would have had at least 297 anaphylaxis events.
- 100% reaction rate with exposure - 297 events
- 50% reaction rate - 148 events
- 25% reaction rate - 74 events
- 20% reaction rate - 60 events
There were 60 events of anaphylaxis in the study.
Also, consider 413 subjects on peanut OIT -intention to treat. The intent was a year of treatment. That would be 150,745 days of peanut exposure. However there were drop-outs from the study. In PALISADES there were 372 who were exposed to peanut OIT for a year- 135,780 exposures to peanut protein. There were 60 anaphylactic reactions
- 0.0004 anaphylactic events per exposure or
- 1 episode of anaphylaxis per 2,500 exposures to the product.
Clearly we need to worry about anaphylaxis, peanut OIT is not a guarantee for no anaphylaxis, but it does offer some protection.
FEL 6/10/2019
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