This case is about Merck's efforts
for more than a decade to defraud the United States with respect
to the efficacy of
Merck's mumps vaccine.
The FDA insists on such a high efficacy rate (95%) because only
then can the disease ultimately be eradicated through what is
commonly referred to as "herd immunity."
Without demonstrating that its mumps vaccine continued to be 95%
effective, Merck would lose its exclusive license to manufacture
and sell its MMRII vaccine.
Relators Krahling and Wlochowski participated on the team that
conducted this supposedly enhanced test. Each of them witnessed
firsthand the falsification of the test data in which Merck
engaged to reach its 95% efficacy threshold. In fact, each was
significantly pressured by Krah and other senior Merck personnel
to "participate in this fraud."
Merck added rabbit antibodies for the singular purpose of
altering the outcome of the test by increasing the virus
neutralization count.
Without applying a proper "control" to the process, there is no
way to isolate whether virus neutralization is caused by the
human antibodies alone or in combination with the rabbit's
antibodies, Merck did not apply this kind of control.
And adding rabbit antibodies as a supplement to a vaccine was
not an option because it could result in serious complications
to a human, even death.
"Merck's senior management" helped
orchestrate the vaccine fraud
Krah did not act alone in orchestrating the falsification of
Merck's mumps vaccine test results. He acted with the authority
and approval of Merck's senior management.
In July, Relator Krahling met with Alan Shaw, Merck's Executive
Director of Vaccine Research and complained to him about the
fraudulent vaccine testing.
Shaw talked about the significant bonuses that Emini had
promised to pay once the testing was complete.
Relator Krahling then met with Bob Suter, Krahling's human
resources representative at Merck. Krahling told Suter about the
falsification of testing data and Shaw's refusal to get
involved. Krahling told Suter that he was going to report the
activity to the FDA.
Suter told him he would go to jail if he
contacted the FDA and offered to set up a private meeting with
Emini where Krahling could discuss his concerns.
Emini agreed that Krah had misrepresented the data. Krahling
also complained about the use of rabbit antibodies to inflate
the seroconversion rate. Emini responded that the rabbit
antibodies were necessary for Merck to achieve the project's
objective.
"Destroyed evidence"
The next morning, Krah arrived early to the lab and packaged up
and destroyed evidence of the ongoing Protocol 007 efficacy
testing.
This included garbage bags full of
the experimental plates that would have (and should have) been
maintained for review until the testing was complete and final.
Despite the threats he received from Suter and Emini, Krahling
called the FDA to report this activity and Merck's ongoing
fraud.
On August 6, 2001, in response to
Krahling's call, an FDA agent came to Merck to question Krah and
Shaw... And she did not address the actual destruction of
evidence that Krah had already facilitated.
"Wide-scale falsification of test
data"
What no one knew outside of Merck - not the FDA, the CDC or any
other governmental agency - was that this result was the product
of Merck's improper use of rabbit antibodies and the wide-scale
falsification of test data to conceal the inflated
seroconversion numbers these antibodies generated.
In 2005, the FDA granted Merck approval and an exclusive U.S.
license for its ProQuad vaccine. Merck obtained the license
continuing to misrepresent the efficacy of its mumps vaccine.
Around the same time, the EMA also approved Sanofi Pasteur MSD's
application for sale of Merck's ProQuad in Europe. As with
MMRVaxPro, Merck's joint venture submitted the falsified results
of Protocol 007 to the EMA as supportive clinical information in
its vaccine application.
In 2006, more than 6,500 cases of mumps were reported in the
Mid-West. This was the largest mumps outbreak in almost twenty
years...
The CDC, FDA and Merck publicly worked together to determine the
cause of this 2006 outbreak. Of course, only Merck knew that the
primary cause was the insufficient efficacy of its vaccine.
"Flawed vaccine is the primary cause
of the outbreaks"
The reason for these continued outbreaks is that Merck's vaccine
docs not have a 95 percent efficacy rate.
The vaccine may have been 95 percent
effective when it was originally licensed in 1967, but the
vaccine virus has been waning as it is continually "passaged"...
Without demonstrating that its mumps vaccine continued to be 95
percent effective, Merck would lose its exclusive license to
manufacture and sell its MMRII vaccine. And if Merck lost the
license for MMRII, Merck would also be unable to secure FDA
approval for its ProQuad vaccine. So, Merck set out to conduct
testing of its mumps vaccine that would guarantee an efficacy
rate of 95 percent or higher.
It did this through manipulating its testing procedures and
falsifying the test results. Relators Krahling and Wlochowski
participated on the Merck team that conducted this testing and
witnessed firsthand the fraud in which Merck engaged to reach
its desired results. Merck internally referred to the testing as
Protocol 007. 25.
While Merck's PRN test was modeled after the efficacy test
generally accepted in the industry, it diverged from this "gold
standard" test in a significant way. It did not test the vaccine
for its ability to protect against a "wild-type" mumps virus. A
wild-type virus is a strain of the virus as it exists in nature
and would confront a person in the real world.
That is the type of real-life virus
against which vaccines are generally tested.
Instead, Merck tested the children's
blood for its capacity to neutralise the same Jeryl Lynn mumps
strain with which the children were vaccinated. The children's
vaccine response was not tested for its capacity to neutralize
virulent, disease-causing mumps virus.
The use of the Jeryl Lynn strain, as opposed to a virulent
wild-type strain, subverted the fundamental purpose of the PRN
test which was to measure the vaccine's ability to provide
protection against a disease-causing mumps virus that a child
would actually face in real life.
The end result of this deviation
from foe accepted PRN gold standard test was that Merck's test
overstated thee vaccine's effectiveness.
"Falsification of the test data"
Merck's Improper Use of Rabbit Antibodies In 1ts "Enhanced" PRN
Test
The second test Merck employed under Protocol 007 was formally
called the Anti-IgQ Enhanced Mumps Plaque Reduction
Neutralization Assay. It was commenced in 2000 and again led by
Krah and hia staff at Merck's West Point facility.
Relators Krahling and Wlochowski
participated on the team that conducted this supposedly enhanced
test. Each of them witnessed firsthand the falsification of the
test data in which Merck engaged to reach its 95 percent
efficacy threshold.
In fact, each was significantly
pressured by Krah and other senior Merck personnel to
participate in this fraud.
But the use of the rabbit antibodies allowed Merck to achieve
its high seroconversion objectives. In fact, the exact same
paired blood samples that were found under Merck's original PRN
test to lack sufficient virus neutralizing antibodies were now
considered seroconverted under the "enhanced" test.
Indeed, in one panel of sixty paired
blood samples that had failed the original PRN test, Merck
measured a seroconversion rate of 100 percent! ln other words,
non-neutralizing concentrations of antibodies that would never
protect a child from mumps in the real world were under Merck's
"enhanced" test treated as vaccine successful solely because of
the additional neutralization provided by the rabbit antibodies.
Specifically, Krah and Yagodich and other members of Krah's
staff falsified the test results to ensure a pre-positive
neutralization rate of below 10 percent. They did this by
fabricating their plaque counts on the pre-vaccination blood
samples, counting plaques that were not actually there.
With these inflated plaque counts,
Merck was able to count as pre-negative those blood samples that
would have otherwise been counted as pre-positive because of the
increased neutralization caused by the rabbit antibodies.
"Falsification [was] broad-based
and systematic..."
Merck's falsification of the pre- vaccination plaque counts was
performed in a broad-based and systematic manner:
Krah stressed to his staff that
that the high number of pre-positives they were finding was
a problem that needed to be fixed.
Krah directed his staff to re-check any sample found to be
pre-positive to see if more plaques could be found to
convert the sample to a pre-negative.
Krah and Yagodicii falsified plaque counts to convert
pre-positives to pre-negatives, and directed other staff
scientists to do the same.
Krah appointed Yagodich and two others to "audit" the
testing that other staff scientists had performed. These
audits were limited to finding additional plaques on
pre-positive samples thereby rendering them pre-negatives.
Krah instituted several measures to isolate the pre-positive
samples, facilitate their "re-count" and consequent
conversion to pro-negatives, and minimize the chances of
detection. Those included destroying test results,
substituting original counting sheets with "clean" sheets,
and entering and changing test results directly onto
electronic (excel) spreadsheets that left no paper trail.
Merck cancelled a planned outsource of the efficacy testing
to a lab in Ohio because the outside lab was unable to
replicate the seroconversion results Krah was obtaining in
his lab. Krah and his staff conducted all the testing
instead.
Unsurprisingly, none of the
"recounting" and "retesting" that Merck performed as part of its
"enhanced' PRN testing was performed on any post-vaccination
samples or on any pro-vaccination samples that were
pre-negative.
This additional "rigor" was only
applied to the pre-positive samples, the very samples that were
keeping Merck from achieving the requisite 95 percent
seroconversion threshold.
"A trillion to one"
In July 2001, Relators Krahling and Wlochowski conducted their
own test to confirm statistically what they already knew to be
true.
They reviewed approximately 20
percent of the data that Merck had collected as part of the
"enhanced" PRN test. In this sampling, they found that 45
percent of the pre-positive data had been altered to make it
pre-negative.
No pre-negatives were changed to
pre-positives. No post-positives were changed to post-negatives.
No post-negatives were changed to post-positives. All changes
were in one direction - reducing the incidence of pre-positives.
The statistical probability of so many innocent changes
occurring in just the pre-positive data and in no other data was
more than a trillion to one.
And that is a conservative measure
given the likelihood that an even greater number of
pre-positives were changed but remained undetected because the
changes were not recorded in Merck's files.
"Acted with the authority and
approval of Merck's senior management" - The Complicity of
Merck's Senior Management
Krah did not act alone in orchestrating the falsification of
Merck's mumps vaccine test results. He acted with the authority
and approval of Merck's senior management.
In April 2001, for example, Emilio Emini, the Vice President of
Merck's Vaccine Research Division, held a meeting with Krah and
his staff where he directed them to follow Krah's orders to
ensure the "enhanced" PRN testing would be successful.
He also told the staff,
Krah's orders to ensure the
"enhanced" PRN testing would be successful. He also told the
staff that they had earned very large bonuses for their work
so far on the project and that he was going to double the
bonuses mid pay them once the testing was complete.
In July 2001, Relator Krahling met
with Alan Shaw, Merck's Executive Director of Vaccine Research,
and complained to him about the fraudulent vaccine testing.
Krahling presumed that Shaw already
knew about the fraud since he visited Krah's lab frequently and
almost certainly would have witnessed the changing of
pre-positive data that Krah was openly directing.
Nevertheless, Krahling wanted to put
Shaw on formal notice of the fraud end told him of the
falsification of the pre-positive data. He also complained about
the improper use of the rabbit antibodies to inflate the
post-vaccine neutralization counts. Shaw responded that the FDA
permitted the use of rabbit antibodies and that that should be
good enough for Krahling.
Shaw refused to discuss anything
further about the matter. Instead, Shaw talked about the
significant bonuses that Emini had promised to pay once the
testing was complete.
"Threatened with jail time"
Relator Krahling then met with Bob Suter, Krahling's human
resources representative at Merck.
Krahling told Suter about the
falsification of testing data and Shaw's refusal to get
involved. Krahling told Suter that he was going to report the
activity to the FDA. Suter told him he would go to jail if he
contacted the FDA and offered to set up a private meeting with
Emini where Krahling could discuss his concerns.
Shortly thereafter, Emini agreed to meet with Krahling. Krahling
brought to the meeting actual testing samples and plaque
counting sheets to demonstrate to Emini the fraudulent testing
that Krah waa directing.
Emini agreed that Krah had
misrepresented the data. Krahliug also complained about the use
of rabbit antibodies to inflate the seroconversion rate. Emini
responded that the rabbit antibodies were necessary for Merck to
achieve the project's objective. Krahling proposed a scientific
solution to lower the pre-positive rate and end the need to
falsify data - stop using rabbit antibodies.
When Emini declined, Krahling asked
him what scientific rationale justified using the rabbit
antibodies. Rraini explained that Merck's choice to use these
antibodies was a "business decision."
The next morning, Krah arrived early to the lab and packed up
and destroyed evidence of the ongoing Protocol 007 efficacy
testing. This included garbage bags full of the experimental
plates that would have (and should have) been maintained for
review until the testing was complete and final.
Despite the threats he received from
Suter and Emini, Krahling called the FDA to report this activity
and Merck's ongoing fraud.
"FDA overlooked the vaccine fraud"
The FDA issued a one page deficiency report identifying a few
relatively minor shortcomings in Merck's testing process. These
principally related to flaws in Merck's record-keeping and in
its validation/explanation of changes to the test data.
The report did not address nor censure Merck for any issues
relating to Merck's improper use of rabbit antibodies or Merck's
wide-scale falsification of pre-positive test data. The FDA did
not discover this fraudulent activity in the course of their
perfunctory visit because of Krah's and Shaw's
misrepresentations to the FDA.
In order to comply with the deficiency report, Merck made minor
adjustments to its testing procedure relating to its heretofore
ad hoc procedure for counting plaques.
"Wide-scale falsification of
[vaccine] test data"
Merck completed its Project 007 testing in late summer or early
fall 2001. Unsurprisingly, the results Merck reported fell
within the 95 percent seroconversion target Merck had from the
outset.
This is the result Merck provided
the FDA and the public at large.
What no one knew outside of Merck -
not the FDA, the CDC or any other governmental agency - was that
this result was the product of Merck's improper use of rabbit
antibodies and the wide-scale falsification of test data to
conceal the inflated seroconversion numbers these antibodies
generated.
