Comment by oldstrangers | Hacker News Reader

Comment by oldstrangers | Hacker News Reader

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Merck, makers of Bravecto, say isoxazoline class drugs are safe... That's probably not a great source.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7738705/

The consolidated FDA, Project Jake and EMA findings (Table 8) showed notable differences between survey populations regarding the percentage of neurological toxicity and serious AE, and fatal effects. Statistical analysis of these serious AE showed highly significant differences between the findings of the Project Jake survey and those reported by the FDA and EMA. While the number of death and seizure AE reported by the EMA was 7 to 10 times higher than those reported to the FDA, the reported responses for the Project Jake survey for death and seizures fell in between those of the FDA and EMA but aligned more closely with the EMA results. Furthermore, the number of reported death and seizure AE for lotilaner and spinosad were considerably higher than suggested with respect to their product labelling for potential neurological effects (Table 2 and and8).8).

But yes, the drug is "generally" safe for use. It's still worth being aware of the potential risks.

The link you posted has a notice right at the top saying the article has been corrected.

It links to a corrigendum adding a conflict of interest disclosure stating

> A Class Action lawsuit related to the use and safety of isoxazoline parasiticides was filed on December 27, 2019 in New Jersey, while this manuscript was undergoing peer review. One of the article's co‐authors, Valerie Palmieri, is the Plaintiff. [PALMIERI, et al. v. INTERVET INC, Case No. .2:19‐cv‐22024‐JMV‐AME (D. N. J.).]”

Correct, a conflict of interest for sure, but it's still a peer reviewed paper regardless.

It has several red flags, IMO.

#1: Authorship is a big one, and the conflict of interest developing during the review process shows that these are not disinterested researchers.

#2: The type of study is a nearly worthless type, in that it has no real statistical control and is just asking people to report on things on the internet. What ends up happening with these studies is that people self-recruit by word of mouth. Survey respondents may have been asked by other participants to register adverse events, and survey respondents may have never given the medication to a pet or seen an adverse event. There is no controlling for that apparent in the study.

#3: The survey instrument is supposed to be in the appendix and it is not, yet it is not described. Their recruitment process is described only as "distributed electronically by mail throughout the United States to veterinarians, veterinary clients, pet caregivers/owners, kennel club groups and on social media sites between August 1 and 31, 2018." There are lots of complaints about the adverse-event reporting system, the worst is that adverse events are merely enumerated from reports and there is no real way to put them into a statistical study. This is just getting another enumeration of events and putting a different denominator under them.

In my prescribing I have seen only one adverse event worth reporting: a dog was heartworm positive and received ivermectin, doxycycline and afoxolaner at the same time. It had a transient episode of low blood pressure treated with fluids. For a drug that, in their denominator, gives 80+% adverse reactions, that is very surprising. So, the study doesn't really pass the smell test.

There have been other drugs that have caused adverse reactions in significant numbers of patients. We stop using them immediately. The difference is very noticeable.

OMG, I went down the rabbit hole on this paper and it is bonkers. Their methodology is amateur hour. It's just an uncontrolled non-validated survey sent out by an activist group. What is their list of survey recipients based on? What were the demographic differences between responders and nonresponders? It's the science equivalent of a political push-poll (https://en.wikipedia.org/wiki/Push_poll)

The first author is a business executive who launched a huge class-action against Merck without disclosing it in this paper, the only veterinarian in the authors has been cited for practicing without a license (https://www.ocregister.com/2021/10/26/founder-of-hemopet-in-...) and the senior author is an orthopedic surgeon with no relation to the field and has maybe one other publication.

Come on, this is not a serious paper.

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