Saturday, March 9, 2019

Transparent Citation Kiting in the 2013 and 2014 EAS “consensus” of experts: how to carry a conclusion without having to reach it.

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Transparent citation kiting in the 2013 EAS “consensus statement”

The 2013 “consensus statement of the European Atherosclerosis Society” was published in the European Heart Journal. It can be seen below, on the right. It is the most influential statement of FH prevalence in the industry, found in FDA documents, investor presentations, patient brochures, and even in SEC 10-K filings. It puts FH prevalence at 1/200. This number is converted in the 2014 EAS statement through the “Hardy-Weinberg” equation to the HoFH population of 1/160,000.  I found many shenanigans in these reports, and I hope to go public with those in separate presentations. For the present purposes, we’ll focus on the linguistic manipulation executed by way of citation kiting. On the left is Dr. Rader’s 2003 report, with the established definition of FH: it is distinct from the APOB and PCSK9 carriers. On the right is the 2013 EAS report which cites Dr. Rader’s paper, but it conflates the diseases together.  Combining FH, FDB, and FH3 in the 2003 report on the left leaves us with 1 in 300.  Most of the 1 in 200 in the 2013 report on the right is due to this linguistic maneuver.  (As for getting from 1 in 300 to 1 in 200, I will cover that in a separate presentation.)

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Pharma-funded publications are using readers’ suspended attention between publications to leave out facts, definitions, and even key numbers.  I’ve referred to this removal during the researchers’ transfer of information as a “fact-ectomy.” As for “citation kiting,” like check kiting, it claims a value on paper which persists as a value only as long as that claim remains unreconciled with its source. The scheme is easy to see, once we’re looking for it. We just trace the “citation” back to its source, match up quantities claimed in each, account for “innovative” definitions, and then set up their respective values and terms side by side. With citation kiting, what we see is something like a relay team that cheats by switching batons, instead of passing on the original. In SEC 10-K filings this 2014 EAS report is the source for the HoFH prevalence of 1/300,000. (It also takes the 2013 EAS HeFH number and through derivation cites 1/160,000 for HoFH.)  It’s not epidemiology.  It’s a gimmick. 

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Is there a good reason for blending different diseases under the name of one of them? Compound HeFH will soon be HoFH. What happens when we hold to the historical record, and tease the underlying components out from their new names? As with all of the FH studies that I have found, the claim of doubled, tripled, even sextupled prevalence is not only refuted by the studies’ own raw data, but the old numbers are confirmed by the very data used to claim a refutation. Restoring citation and linguistic integrity alone recovers the underlying math. Prevalence for HoFH was said to be 1 in 1,000,000. In the Dutch study, there were 20 HoFH found. But 4 of those were said to “inflate the prevalence,” so they were explicitly removed, leaving 16 employed in off-text calculations: this key HoFH number “16” is nowhere to be found in the entire report. And this report is on the homozygous, yet a prevalence number for the true homozygous FH is not in the text. True HoFH is 1/1,045,149, astonishingly close to the established number. Yet this result will not be mentioned, not here, not in the 2014 EAS. This Dutch study will blend in compound heterozygous FH and call both of them combined, the “HoFH.”  Then 2014 EAS will take that number and add in the HoFDB, and simply call of these, “HoFH.”

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Which Wall Street companies are interested in FH Prevalence?

Big players like Amgen, Regeneron, Sanofi, Merck, and others are financially interested in FH prevalence. However, Novelion (NVLN), Gemphire (GEMP), Madrigal (MDGL) and Esperion (ESPR) are also valued according to how large or small the FH population might be. These four companies go the extra mile and actually claim prevalence estimates in their annual reports filed with the SEC. Below are screenshots I took last year of the 2017 10-K’s. The same claims are made in the 2018 10-Ks.  All four claims depend upon “consensus" reports, which actually conducted no prevalence studies of their own. After chasing the literary references down to their sources, the stones upon which these prevalence claims are built are not scientific. They are linguistic and depend upon preserving asymmetry between what the authors and their readers know.  The 2014 EAS HoFH prevelance estimates – 1 in 300,000 and 1 in 160,000 – are derived from citation kiting. This results in the the equivocation of the (1) genetic definition of the disease and (2) diagnosed FH. Of these two, we will first look into the former, the linguistic equivocation of the genetic defintion of FH. In a separate presentation, I will provide evidence of the equivocation of “FH” through the removal of key elements/steps in the diagnostic procedure.

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Here is what an increased prevalence means ... and doesn't mean. For prevalence of homozygous FH, the difference between the Danish result of 1/160,000 and the Dutch result of 1/300,000 is large, but we must also remember that the original estimate by the Nobel Prize winner was 1/1,000,000. Even if we just consider Novelion, and not the entire industry, we can see what is at stake. What will shares of Novelion be worth with this or that prevalence figure? When raising money from investors, what value will investors place on such a company after the Dutch report? The annual price of Aegerion/Novelion’s drug, Juxtapid, has ranged from $290,000 to well over $300,000 during the last 5 years. To create a rough sketch, I used $300,000 to represent the price over these years and 320 million for the U.S. population. Then I calculated the annual addressable market per prevalence estimate according to the Danish and Dutch reports.  I set these two estimates between Aegerion/Novelion’s actual Juxtapid U.S. sales during the last 5 years and an addressable market in accordance with the Nobel Prize winners’ estimate. 

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