Excerpted From the House of Representatives Gov't Reform Committee Staff
Application to the FDA
December 9, 1994
Fred Clark, Paul Offit, Stanley
Plotkin (Inventors); Wistar
Institute of Anatomy and
Biology and Children's Hospital
of Pennsylvania (Assignees)
Filed U.S. Patent for
Rotavirus reassortant vaccine.
Application number 353547
Dr. Offit shares the patent on the Rotavirus vaccine
in development by Merck and lists a $350,000 grant from Merck for Rotavirus
vaccine development. Also, he lists that he is a consultant to Merck.
c. Dr. Paul Offit
Dr. Offit lists that he is a consultant to Merck on an
attachment to his OGE 450, but does not disclose whether or not he received any
remuneration for his services.
Dr. Offit began his tenure on ACIP in October of
1998. Out of four votes pertaining to the ACIP’s rotavirus statement he
voted “yes” three times, including, voting for the inclusion of the rotavirus
vaccine in the VFC program.
Dr. Offit abstained from voting on the ACIP’s
rescission of the recommendation of the rotavirus vaccine for routine use. He
stated at the meeting, “I’m not conflicted with Wyeth, but because I consult
with Merck on the development of rotavirus vaccine, I would still prefer
to abstain because it creates a perception of conflict.”[lxvii]
In the hearings in the House
He was questioned continually by Dan Burton, Congressman in the Conflict of
Interest Hearings in D.C. about his conflicts and he ABSOLUTELY denied that the
above made a conflict because he was an honest man.
Vaccine-Preventable Diseases Rotavirus vaccines on the horizon offer some
hope Future vaccines may include bovine and attenuated human rotavirus strains.by
SEATTLE – Future rotavirus vaccines may include both bovine and attenuated human
rotavirus strains. They are believed to be unlikely to induce intussusception,
and should still be effective, according to Paul Offit, MD, who spoke here at
the Pediatric Academic Societies meeting.
Offit, of the Children’s Hospital of Philadelphia, at the University of
Pennsylvania School of Medicine, said there are two new rotavirus vaccines on
the horizon that may make a dent in the tremendous disease burden caused by
In developing countries, rotavirus is a deadly disease, accounting for
approximately 660,000 to 800,000 deaths a year from severe dehydration. It is
because of the disease burden that a vaccine is needed, Offit said.
Initially, the first rotavirus vaccine, the live, oral tetravalent RotaShield (RRV-TV,
Wyeth-Ayerst) vaccine was developed using a simian rotavirus.
The approval of RotaShield in 1998 was based on positive evaluation of efficacy
data from five, large clinical efficacy trials conducted in the United States
and Europe. Offit said that the vaccine was about 48% to 68% protective against
disease. There were some adverse events, including fever, decreased appetite,
irritability and decreased activity after the first dose — these events were not
observed after the second dose.
Another problem noted before the vaccine was licensed was intussusception. It
was noted in five of 10,992 vaccine recipients, and one per 4,633 placebo
recipients. According to Offit, this fact was worrisome enough to be included in
the package insert.
About one year after the vaccine was licensed, a Morbidity and Mortality Weekly
Report noted 15 cases of intussusception, 13 of which had occurred after the
first dose and 11 of which had occurred within seven days of the vaccine’s
The CDC suspended use of the vaccine while a case study was performed, and after
that study, researchers determined that the relative risk was highest after the
first dose, and declined after the second dose. The risk for intussusception was
about one case per 10,000 vaccine recipients. Because of the risk of
intussusception, the vaccine’s manufacturer pulled the vaccine from shelves and
health officials suspended its use.
During the time that RRV-TV was available, approximately 1 million American
infants were immunized, and one child died of vaccine-related intussusception.
“One could argue the benefits of the vaccine still outweighed its risk,” Offit
said. “There would be far fewer hospitalizations and deaths from intussusception
than from rotavirus disease.”
Vaccines in the pipeline
The fact that the vaccine has been pulled from shelves left other companies
looking for alternative vaccine strategies. So far, most candidate vaccines
against rotavirus have been based on live, weakened animal strains of the virus.
These animal strains were used at first, in part, because they grew easily in
cell cultures. RRV-TV is based on a strain from the rhesus macaque, but Merck
has a candidate based on a bovine strain known as WC3 (RotaTeq).
In developing countries, rotavirus is a deadly disease, accounting for
approximately 660,000 to 800,000 deaths a year from severe dehydration.
The WC3 vaccine is a liquid, buffered vaccine that has been administered orally
on the two-, four-, six-month and two-, three-, four-month schedule in clinical
trials. It is a multivalent vaccine with specificity against the four serotypes
— G1, G2, G3 and G4, that are responsible for more than 85% of rotavirus
In several placebo-controlled studies done to date, WC3 and its parent vaccines
have been generally well tolerated and efficacious. No statistically significant
increase in the incidences of fever, irritability, vomiting, or diarrhea has
been observed in vaccine as compared with placebo recipients. For example, in a
study of 439 infants, 15.7% of vaccine recipients vs. 14.1% of placebo
recipients had fever during the two-week period after dose 1. The proportion of
patients who shed vaccine in stools is low, ranging from 3.3% to 4.4% during the
three to five days after vaccination.
Offit said a completed study of 1,946 infants who were followed for
gastroenteritis throughout the rotavirus season after vaccination, suggests that
RotaTeq was 68.8% to 76.6% efficacious in preventing any rotavirus disease
regardless of severity or serotype. Preliminary immunogenicity results show a
three-fold rise in serum neutralizing antibody titer to G1 in 73.3% to 86.2% of
vaccinees, and a three-fold rise in rotavirus-specific serum IgA in >90% of
A large study is underway to evaluate the safety of the vaccine with respect to
serious adverse experiences such as intussusception. He said no evidence of
intussusception associated with the new vaccine has been noted, yet, in 45,000
infants in clinical trials.
Another option for a rotavirus vaccine lies with the attenuated human rotavirus
vaccine (RotaRix, GlaxoSmithKline). Offit said this a phase-2 efficacy study of
215 infants had positive results, with approximately 90% of the vaccinated
infants protected from rotavirus and a statistical significance at P<0.001.
Examination of the safety data revealed only mild transient symptoms including
fever in a small number of infants.
For more information:
Offit P. New rotavirus vaccines: after Rotashield. Topic symposium 5654.
Presented at the Pediatric Academic Societies meeting. May 3-6, 2003. Seattle.
Dr. Offit is a coholder of the patent on bovine-human reassortant rotavirus
vaccine currently being developed by Merck.
Safety, efficacy, and immunogenicity of a live,
quadrivalent human-bovine reassortant rotavirus vaccine in healthy infants.
Clark HF, Bernstein DI, Dennehy PH, Offit P, Pichichero M, Treanor J, Ward RL,
Krah DL, Shaw A, Dallas MJ, Laura D, Eiden JJ, Ivanoff N, Kaplan KM, Heaton
University of Pennsylvania School of Medicine, Philadelphia, and Merck & Co,
Inc, West Point, Pennsylvania USA.
OBJECTIVES: To investigate safety, efficacy, and immunogenicity of live
quadrivalent rotavirus vaccine (QRV) containing human-bovine (WC3)
reassortant rotavirus serotypes G1, G2, G3, and P1a.Study design This was a
randomized, double-blinded, placebo-controlled trial. During 1993 to 1994, at
10 US study sites, 439 healthy infants approximately 2 to 6 months of age,
were enrolled to
receive 3 doses of oral QRV or placebo at approximately 8-week intervals.
RESULTS: The vaccine was generally well tolerated; no serious vaccine-related
adverse experiences were reported. Risk differences and 95% confidence
intervals suggested no differences between vaccine and placebo recipients in
the incidences of fever, irritability, vomiting, or diarrhea during the 14
days after any dose. QRV was 74.6% efficacious (95% CI: 49.5%, 88.3%) in
preventing rotavirus acute gastroenteritis (AGE), regardless of severity and
100% efficacious (95% CI: 43.5%, 100%) in preventing severe rotavirus AGE
through one rotavirus season. Serotype G1 was identified in most infants with
rotavirus AGE. A >/=3-fold rise in serum neutralizing antibody to G1 was
observed in 57% (45/79) of vaccinees. A >/=3-fold rise in serum
anti-rotavirus IgA and fecal anti-rotavirus IgA was observed in 88% (162/185)
and 65% (104/159) of vaccinees, respectively. CONCLUSIONS: QRV was generally
well tolerated, immungenic, and highly effective against rotavirus
PMID: 14760258 [PubMed - in process]
VACCINE EXPERT OFFIT DODGES VACCINE-MERCURY DEBATE ON MSNBC,
NATIONAL AUTISM ASSOCIATION
For Immediate Release:
June 24, 2005
Laura Bono, NAA (NC) 919-403-9443
Jo Pike, NAA (SC) 843-206-8443
Rita Shreffler, NAA (MO) 417-725-6107
Wendy Fournier, NAA (RI) 401-632-7523
VACCINE EXPERT OFFIT DODGES VACCINE-MERCURY DEBATE ON MSNBC, SAYS NATIONAL
DR. PAUL OFFIT AND OTHER EXPERTS AGAIN DECLINE DEBATE ON THIMEROSAL ISSUE
New York, NY - Yesterday on MSNBC's Connection: Coast-to-Coast, Dr. Paul Offit,
Chief of Infectious Diseases at the Children's Hospital of Philadelphia,
declined to argue his case that mercury in vaccines is safe. The one-hour
segment featured Offit, along with Dr. Louis Cooper, former President of the AAP.
Both requested not to debate journalist David Kirby, whose best-selling book
Evidence of Harm demonstrates a growing body of evidence that mercury in
vaccines and other products cause autism.
Many wonder why pro-mercury experts, who tout thimerosal's safety, continue to
shy away from healthy questioning. Richard Copeland (Springfield, OH)
grandparent of a child with autism says, "This is how people act when they have
something to hide."
More from Dr. Offit and Dr. Cooper:
- Offit contradicted his earlier public statements that the rise in autism is
real, citing the criteria for autism may have simply been "loosened." Multiple
studies conducted by UC Davis and Pediatrics conclude the rise is real.
- At a 2004 meeting in Chapel Hill, NC, Offit suggested that something must be
happening during pregnancy to cause autism, yet thimerosal is a post-natal
toxin. A mother pointed out that thimerosal is also given pre-natally via
immunoglobulins such as RhoGAM. Offit replied, "[Thimerosal] shouldn't have been
- On MSNBC, Offit made reference to Swine-flu vaccines causing Guillain-Barre,
an autoimmune disorder. In Chapel Hill, Offit claimed that "no vaccine has ever
caused an autoimmune disorder." Many feel autism is autoimmune related.
- On MSNBC, Offit discussed the "massive inadvertent mercury poisoning" in Iraq
in the early 70's, stating that pregnant Iraqi mothers who ate mercury-laden
food had babies with mental retardation and seizure disorders, not autism.
However, mental retardation and seizure disorders are sub-symptoms of autism, as
well as hearing problems, digestive problems, kidney issues and other symptoms
associated with the Iraqi poisoning.
- Offit claimed it is "very simple" to do retrospective epidemiological studies;
however, the CDC had to do their epidemiological study five times, one of which
found a connection but was never released.
- Offit said the epidemiological studies were "carefully performed." Yet, in
2004 National Journal quoted Dr. Robert Davis admitting they allowed newborn
babies into the inclusion criteria, even though newborns are too young to be
diagnosed with autism.
- Offit said that mercury (a neurotoxin) causing autism (a neurodevelopmental
disorder) does not make biological sense. Yet, in October 2001, the IOM
concluded that it was "biologically plausible."
- Dr. Cooper suggested the simultaneous increase between the rise in autism, now
affecting 1 in 166 children, and vaccine-based thimerosal, is a mere
"coincidence." Many feel that autism, which was first diagnosed right around the
same time thimerosal was introduced, is also a coincidence. Further, pro-mercury
advocates feel that parental reports of their children's immediate regression
following a thimerosal-based vaccine, is also a coincidence.
Offit championed epidemiological studies which mainly work off numbers and
statistics. Earlier in the segment, Kirby pointed out that major universities
have performed peer-reviewed biological studies, a more powerful indicator of
causation. These studies suggest mercury-based thimerosal causes autistic-like
behaviors. The behavioral and medical symptoms of autism and mercury poisoning
are virtually identical. To view these studies, please visit
Think Autism. Think Cure.
National Autism Association | PO Box 1547 | Marion | SC | 29571
A vaccine for rotavirus (Rotateq) developed by Merck, the
Children's Hospital of Philadelphia and Paul Offit, America's most quoted
promoter and apologist for the vaccine industry, will be considered for
licensure on December 14 and by the Vaccines and Related Biological Products
Advisory Committee of the Center for Biologics Evaluation and Research of the
Offit and his partners Merck and the Chidren's Hospital of Philadelphia, first
received a patent for a rotavirus vaccine in 1994. Offit later voted to add
rotavirus vaccine (a variety from Wyeth not Merck) to the recommended schedule
of vaccines when he was a member of the FDA's Advisory Committee of Immunization
Practices. Despite his ownership of a rotavirus vaccine patent Offit saw no need
to recuse himself from several votes on adding rotavirus to the schedule, which
is one of the last steps to inclusion in the mandatory schedules, and a
guaranteed market worth billions to a vaccine maker, and comes with complete
immunity from lawsuits.
This vaccine was rushed into distribution has quickly shown to cause massive
intestinal damage and death in a small but vulnerable subset of children. It was
just as quickly removed form the market.
According to the FDA website three of the members of the Committee's members
have applied for and received waivers for potential conflicts of interest
Participation of the public is permitted in this meeting:
December 14 - 15, 2005 Meeting
Date and Time:
The meeting will be held on December 14, 2005, 9:00 am to 4:30 pm; and on
December 15, 2005, 9:00 am to 4:30 pm
Holiday Inn Select, 8120 Wisconsin Avenue, Bethesda, MD, 20814, 301-652-2000 .
Christine Walsh, R.N. or Denise Royster, 301-827-0314, or FDA Advisory Committee
Information Line, 1-800-741-8138 (301-443-0572 in the Washington, DC area), code
3014512391. Please call the Information Line for up-to-date information on this
On December 14, 2005, the Committee will hear presentations and make
recommendations on the safety and efficacy of a Rotavirus Vaccine manufactured
by Merck. On December 15, 2005, the Committee will hear presentations and make
recommendations on the safety and efficacy of ZOSTAVAX (Zoster Vaccine Live [Oka/Merck]
) manufactured by Merck.
Between approximately 1:15 and 1:45 pm, on December 14, 2005; and 1:30 and 2:00
pm on December 15, 2005, oral presentations from the public will be scheduled.
Those desiring to make formal oral presentations should notify the contact
person before December 7, 2005.
Paul Offit at The Children's Hospital of Philadelphia developed a vaccine based
on a bovine strain of rotavirus (WC-3). Merck is currently running Phase III
trials of a modified version of his quadravalent reassortant vaccine. Aiming to
avoid the adverse affects that RotaShield® was associated with, the vaccine is
based on a bovine strain of rotavirus. The bovine strain was chosen because it
replicates less prolifically in the human gastrointestinal tract than the simian
strain used for the tetravalent rhesus reassortant vaccine.  Each of the five
reassortants consists of the genetic backbone of the bovine virus with an
inserted gene coding for a different human rotavirus surface protein. The
inserted genes were selected to represent a broad range of serotypes in order to
elicit protection against a wide variety of strains.
Genes coding for four VP7 proteins and one VP4 protein are included in the
reassortants. Human serotypes G1, G2, G3 and G4 are represented by the four VP7
proteins, and serotype P1a is represented by the VP4 protein.  Initial trials
of a similar live quadrivalent human-bovine reassortant vaccine demonstrated
promising protection against rotavirus infection.  Differing from the Merck
vaccine only by the exclusion of serotype G4, this vaccine's results likely
mirror the protection that RotaTeq® will afford.
The quadrivalent vaccine, which was delivered to vaccinees in three oral doses
at 2, 4, and 6 months of age (identical to the Merck vaccine delivery schedule),
showed 74.6% efficacy against any rotavirus infection and 100% efficacy against
severe rotavirus infection. No increase in diarrhea, vomiting, fever or
irritability was reported as compared to the recipients of the placebo. The
immunogenicity of the quadrivalent vaccine was reflected in an increased ratio
of rotavirus specific IgA to total IgA as measured in the vaccinee's stool. 
Licensure of RotaTeq® by the FDA is predicted for 2005 if Phase III trials are
The Cutter Incident: How America's First Polio Vaccine Led to the Growing
Vaccine Crisis -- by M.D., Paul A. Offit
Book Reviewed by John Gilmore
This is a truly bizarre book. Somehow the author Paul Offit, MD, believes
that telling a gripping story about the massive scientific, regulatory and
industrial failures that lead to hundreds of thousands of people in 1955 being
injected with a vaccine containing live polio viruses which resulted in
thousands of people paralyzed for life and hundreds of deaths, would persuade
people now that vaccine manufacturers should be shielded from any legal
liability for their products. That in a nutshell is the purpose of this book.
The first 130 pages tells the compelling story of the development of the
polio vaccine and how a batch of polio vaccine made by Cutter Laboratories
actually gave people the disease it was designed to prevent. This section is
followed by a forty-page analysis of the legal consequences of the Cutter
incident that verges on incoherence. Here Offit seems to make the classic
mistake of physicians who assume they are the leading authority in the room on
all subjects. Somehow Offit believes that a fundamental injustice to the vaccine
industry occurred when juries found that Cutter Laboratories was liable for the
damage created by their product. In Offit’s analysis, as long as the
pharmaceutical company thought the vaccine was safe, injured people should have
no legal recourse. It would seem obvious that shielding firms from liability
creates exactly the kind of environment where Cutter-type incidents would breed.
This section is followed by a brief polemic, more of a rant, filled with
factual errors, demanding the laundry list of political favors lusted after by
the pharmaceutical industry. These demands go far beyond “tort reform,” the
pharmaceutical industry is calling for the repeal of basic constitutional rights
and the undermining of basic principles of American
law to suit the short-term profit needs of a generously campaign-donating
While stating his academic and hospital associations, the book fails to
disclose significant and relevant details of Offit's own financial and business
dealings. In addition to being the leading vaccine promoter in the US, just
google him, he is also a vaccine developer and business partner with Merck,
GlaxoSmithKline and the Children’s Hospital of Philadelphia, who collectively
own a rotavirus vaccine that was recently overcame a major milestone to
+ Continues here: http://www.sarnet.org/lib/SARrev1-16-06.htm
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