Tuesday, March 5, 2019

Intro: Citation Kiting in Peer Reviewed FH Literature.

Introductory explainer video:


Citation Kiting in Peer Reviewed FH Literature
Introductory Explainer Video: a follow-up to yesterday's newsletter. (See sign up, on the right.)


Here is the first youtube videohttps://www.youtube.com/watch?v=fKHYjnfHSjo


The explainer video above illustrates the consequences of citation kiting -- as if they were "Before" and "After" photos.  The 2003 "Rader report" and the 2016 "Regeneron report" expose the linguistic and mathematical "conclusion drift" that took place in the interim. But how was this equivocation scheme executed? In a future presentation, I will display screenshots of specific acts of citation kiting and the resulting equivocation. 

Below is a text version of the above, with a little more detail. 


Citation Kiting in Peer Reviewed FH Literature
Background: The disease “Familial Hypercholesterolemia” is caused by a mutation in a cholesterol receptor (LDLR). To express this relationship in acronyms, FH is caused by LDLR.
 Recently, peer reviewed medical journals have published papers declaring that FH prevalence is twice what it was once thought to be.
 Of course, funding by pharmaceutical companies surrounds these peer reviewed publications, payments to both the authors and the journals.
Here are a few Wall Street traded companies who have (or had) a financial interest in the size of the FH population:
·         NVLN      Novelion Therapeutics Inc. (Aegerion Pharmaceuticals)
·         MDGL     Madrigal Pharmaceuticals Inc.
·         GEMP     Gemphire Therapeutics Inc.
·         ESPR       Esperion Therapeutics Inc.
·         AMGN    Amgen Inc.
·         REGN      Regeneron Pharmaceuticals
·         MRK        Merck & Co. (Had hopes for Anacetrapib 2011 ~ 2017)
·         Companies which market statins also have an interest.

(I have no short positions in any of the companies related to my FH research. The reason for this is that I had declared to certain regulators that I had no financial position in any of these companies. Although I last made that declaration in 2017 and although it appears that regulators are not interested, I will hold myself to that statement going forward.)
I will break down my presentation into two parts. In part 1, I will make the case that the “increased” prevalence number is the result of a linguistic gimmick. As a consequence, the integrity of the scientific record is compromised and the addressable market for FH-targeted drugs is inflated.
How far does this scheme go? In any event, I cannot say that exposing peer reviewed medical literature would be the next “Big Short” – because that institution seems to be untouchable. However, what I will outline is a transparent equivocation scheme, carried out by what I call, “Citation Kiting” – with very serious consequences.
The Procedure for Equivocation: An established historical record receives a “fact-ectomy” and authors carry over the truncated content to a new report and then simply cite the purported source. The fact that the content in the source does not match the content in the destination is conspicuous – but only if readers stop trusting peer reviewers and actually reconcile the citations with the sources. (Fact: the industry’s most authoritative, most highly cited claim of doubled FH prevalence has no external, contemporary source for the number it uses! In a multi-billion-dollar industry, the number just … appears. It takes some time to rub one’s eyes and get past the doubt, “It can’t be this simple.” Stay tuned. It is..)
Citation kiting has two consequences, one of them seemingly trivial (although it is not), and the other obviously serious.
Part 1: “FH” as a genetically inherited disease: A fact-ectomy is performed on category headings and neighboring subcategories.(I will demonstrate how this works in my first two explainer videos.)
Part 2: “FH” as diagnostic procedure: A fact-ectomy is performed on elements and/or steps within the already established diagnostic procedures and screening strategies. 


Citation Kiting consequence: Part 1 Conflate to Bait: “Twice as many FH carriers found!”

Linguistics
Blending the underlying objects under one name.
 Epidemiology
Tracking the underlying objects of the original names.
Past


Call LDLR mutation carriers, “FH”
Call the APOB, “FDB”
Call the PCSK9, “FH3”
Call the entire group, “ADH”
Call p.Arg3558Cys “harmless APOB”
Past “ADH” ≠ past “FH”.
“FH” = 1:500
LDLR = 1:500
APOB = 1:1,000
PCSK9 = 1:2,500
p.Arg3558Cys = 1:1,103
Math Total 1:232
Present
Drop usage of “ADH” and call LDLR, APOB, PCSK9, and p.Arg3558Cys, “FH”
Past “ADH” + p.Arg3558Cys = Present “FH”
“FH” = 1:200~1:250
LDLR = 1:500
APOB = 1:1,000
PCSK9 = 1:2,500
p.Arg3558Cys = 1:1,103
Math Total 1:232
Rational Conclusion
The change is only due to linguistics.
No change or discovery.

Citation Kiting Consequence: Part 2: Switch identification procedures
After conflation of the names of genetic mutations, add a second step -- switch counting procedures to identify different patients.


Screening and Diagnosis -- familial hypercholesterolemia








There is a lot more to this case, and some of it requires an elaborate breakdown and detailed presentation. Other parts are knee-slapping comedy. There is also tragedy.

I hope to present the whole of it, step-by-step, where each unit of the presentation will be undeniably clear. Toward this end, I am trying to put together short explainer videos, walking through not only the evidence, but exposing the actual engineering of equivocation … at the point of commission.
·    
     I will also be posting detailed PDF reports online. Please visit 3footcrowbar.com for announcements.

For now, here is a brief introduction to Part 1 of my future presentations:

How can one increase a prevalence rate without having to find more people?

Linguistics. 

If zebras were suddenly called “horses,” would we have more of either or both in the world? Industry-funded reports on FH are more aptly called linguistic strategies than prevalence studies. Their claim of a higher than expected prevalence is necessary to sound the alarm of “underdiagnosis.”

Here is only one example. The illustration below shows the consequences of citation kiting -- as if they were "Before" and "After" photos.  The 2003 "Rader report" and the 2016 "Regeneron report" expose the linguistic and mathematical "conclusion drift" that took place in the interim. But how was this equivocation scheme executed? In a future presentation, I will display screenshots of specific acts of citation kiting and the resulting equivocation.  Here, I’ve taken screenshots from two FH reports and put them together in the presentation below. 

On the left is a report from 2003, and on the right, Regeneron’s report from 2016. In 2003, FH referred to the presence of an LDLR mutation; FDB was different and referred to an APOB mutation, and FH3 was yet another disease name, and referred to PCSK9. These diseases were all under the umbrella acronym, “ADH” – which spells out to “Autosomal Dominant Hypercholesterolemia.” Now Big Pharma has funded reports which drop the umbrella, “ADH,” and take the subset of ADH named “FH” and promote it to serve as the umbrella term for the other two diseases. FH is no longer alongside FDB and FH3, and the terms to distinguish FDB and FH3 are dropped, and their respective mutations, APOB and PCSK9, are no longer referred to as subsets to “ADH,” but to “FH.” It is as if the peas under the shells labeled “FDB” and “FH3” have been palmed and are next found under the FH “shell,” which now houses all … the LDLR, the APOB and the PCSK9. FH becomes the main set … the entire set.

Illustration of a conclusion drift over the years -- prevalence of FH familial hypercholesterolemia

In Truisms:
·         A whole pie is larger than one of its slices.
·         Recent “FH” as LDLR + APOB + PCSK9 is greater than Nobel Prize winners’ “FH” as LDLR alone.


Bottom right, of the illustration below is a tweet by the lead author of the Regeneron report.
Linguistics and FH prevalence - Familial Hypercholesterolemia


Note that FH-as-LDLR is 1:518 … still roughly the 1:500 estimated by the Nobel Prize winner, Joseph Goldstein. Nonetheless, this report became a jumping point for the lead author to claim on 
Twitter:

“FH is ~twice as common as it was thought to be.” (See illustration above.)

And here is a co-author in a press release. (Orchestrated? Note that the phrase is a virtually identical.)
“The study shows us that FH is about twice as common as it was once thought to be …” 

['Geisinger and Regeneron study finds life-threatening genetic disorder is substantially underdiagnosed,' Dec. 22, 2016]

But FH "was thought to be" FH-as-LDLR, which was estimated to be around 1:500 to begin with, and in this study FH-as-LDLR is still around 1:500.


More to come. 

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