Lawmakers' group providing people's court for grievances
New Hampshire Sunday News (Manchester, NH) - Sunday, May 9, 2010
By NANCY WEST
unhappygrammy-I pray there is some hope for the people of NH. I'm counting on the Redress Grievance Caucus to help my precious grandchildren!
New Hampshire Sunday News
CONCORD -- About a dozen conservative state lawmakers say they have banded together to right wrongs the government has done to citizens in reviving a centuries-old practice known as "redress of grievances."
Their practice has shaken up the New Hampshire judiciary and triggered a run-in with Democratic House Speaker Terie Norelli.
Led by Republican Daniel Itse of Fremont, they call themselves the Legislators' Caucus for Redress of Grievances.
Last summer they started holding listening sessions, hearing from people who believe they have been wronged by government and officials.
They are not allowed to call themselves a committee or commission or label their sessions legislative hearings by agreement with Norelli.
"We listen to the wrong. If we determine that it's a suitable wrong, then we craft legislation to correct the problem," Itse said.
That might mean writing legislation to right a financial injury or destruction of property or any sort of abuse by government, including complaints against judges, Itse said.
"The beauty of redress is it doesn't cost the citizen anything. You don't have to lawyer up to go before the Legislature and say, 'I've been done wrong.' You make your case. If you win, you win," Itse said.
Early roadblock
Norelli initially barred the group from using legislative facilities and posting notices in the House calendar last year, after it sent letters to a district court judge and marital master on House stationery calling itself a council, notifying them of a hearing on a grievance against them and asking them to attend. She later reinstated those privileges.
"I made it clear they could not give the impression they represented an official body of the Legislature," Norelli said.
Norelli believes the group has a right to gather as an ad-hoc caucus, not as an official committee or council, to discuss grievances and as House members file legislation. But she said the caucus has no official standing and cannot use words that imply it has any authority bestowed by the Legislature.
"I don't personally believe it is the Legislature's role to adjudicate all these cases they want to look at. It is my understanding some cases they are reviewing or discussing are pending cases," Norelli said.
In a letter to the caucus, Norelli wrote: "Your letters attempting to summons a judge and marital master to your meeting were inappropriate and misleading and used terminology that I had specifically stated was not appropriate."
Reconsidered ban
After further communication, Norelli reinstated its right to meet in legislative facilities and post notices in the House calendar, with a warning.
"(Any) future letter sent out by your caucus inviting guests to attend your meetings should clearly contain a disclaimer that it in no way represents the Legislative branch of the state nor is it conducting any official business of the Legislature," Norelli wrote.
Howard Zibel, general counsel to the state Supreme Court, has made it clear the judicial branch has no use for the caucus.
"I do not believe the Legislators' Council on Redress of Grievances to be an official body of the House," Zibel wrote to Norelli.
Zibel complained about the group's letters to Judge Lucinda Sadler and Marital Master Philip Cross on House letterhead asking them to provide their "accounts of the events," at a hearing in the Legislative Office Building.
"It is highly irregular for a legislator to use official House of Representative stationery to attempt to summon a judge and marital master to present their account of a case heard in court at an unofficial meeting of legislators," Zibel wrote.
Members of the caucus filed three bills in the Legislature this session trying to oust Sadler, Cross, and Marital Master Michael Garner. Most of the complaints were from parents who believe they were harmed in custody or marital disputes by not getting due process in the court.
Expecting negative reaction
Itse expects all three bills will be voted "ought not to pass" by the Joint Committee on Address, but he is undaunted.
"Next time we'll be smarter," Itse said.
There soon will be a next time as 15 new grievance petitions are in the pipeline that eventually will become legislation, he said.
Several involve the Division for Children, Youth and Families' Nashua office and another is against a teacher for allegedly threatening a student.
Itse said petitions of redress were common in the Legislature from 1784 through 1819, and the judiciary was often the target of them until it exempted itself by a Supreme Court decision, Merrill v. Sherburne, and the filings waned. Scholars say the case outlined the separation of powers between the Legislature and judiciary.
Itse also is planning more listening sessions this summer for new grievants.
A constitutional scholar said the Legislators' Caucus for Redress of Grievances has no special authority, although members say they don't need any in relying on the New Hampshire Constitution Part 1, Articles 31 and 32.
Article 31 says: "The Legislature shall assemble for the redress of public grievances."
Article 32 says: "The people have a right ... to request of the legislative body, by way of petition or remonstrance, redress of the wrongs done them, and of the grievances they suffer."
Richard Hesse, a retired Franklin Pierce Law Center professor and scholar of the New Hampshire Constitution, said the caucus has no constitutional powers.
Article 31 makes it clear the constitution is referring to the Legislature as a body, not individual lawmakers -- or even a group of lawmakers, Hesse said.
"For individual members to act as the whole body, that would be chaos," Hesse said.
"It is very clear to me that the language means the Legislature shall assemble for the redress. I am persuaded to a certainty, it doesn't authorize individual legislators to act in the name of the Legislature," Hesse said.
No power claim
Gregory Sorg, a former legislator and an attorney who advises the caucus, says it doesn't claim any special powers.
"They don't have any particular constitutional authority. All of the individual legislators have the right to speak to their constituents and have them express grievances. All (the caucus) did was assemble a group of legislators together so they could hear the grievances people had at one time," Sorg said.
Sorg said he believes the process will become very popular if the Republican party regains control of the Legislature.
"It shouldn't be a partisan issue, but the Democrats see this as a way for Republicans to demean the judicial branch and that's not what it's about," Sorg said.
Norelli disagreed.
"I think there is a very limited number of members of the House that share their view. This is not a partisan issue, but is a small number of legislators who think this is the role of the general court," Norelli said.
In the long run, Itse believes, the caucus will make government more responsive to its citizens.
"Once the bureaucrats of government know they can be held accountable in a public manner, the abuse of the public will diminish greatly," Itse said.
Ideally, Itse said, all lawmakers would listen to their constituents' grievances, but most don't even know about the practice, although some are beginning to question him about it.
"Right now, the only place to go is before us," Itse said.
"I'm getting converts, slowly but surely."
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Record Number: mandc5-5ucvwnmht11b2mvl37p
Copyright, 2010, Union Leader Corp.
Isabella Brooke Knightly and Austin Gamez-Knightly
In Memory of my Loving Husband, William F. Knightly Jr. Murdered by ILLEGAL Palliative Care at a Nashua, NH Hospital
Thursday, May 13, 2010
Child Rape Beatings Mass Graves Juvenile Reform Center, Florida ‘White House Boys’
Child Rape Beatings Mass Graves Juvenile Reform Center, Florida ‘White House Boys’
by ADMIN on MAY 12, 2010
This is standard operating procedure in the U.S., hence all the raped, abused, and dead babies and toddlers laying around while in CPS custody/oversight, or adopted, or in juvenile “reform” centers – all havens for pedophiles. See links at bottom. — “The White House Boys” Trailer, the horrifying true story of a reform school in Mariana, Florida in the 1950s whose administrators raped, abused and killed young boys. After victims came forward demanding justice the Governor of Florida launched a mandatory investigation to uncover the truth behind the hundreds of unmarked graves located at the school. Families insisted that their lost children were buried there after being beaten to death in the White House. Based on the book “The White House Boys” by Roger Kiser. This is a sneak peak to the documentary and film presented to you by Franchesca Elder and Paul Hensler.
“White House Boys” Sue State Over Abuse at Florida State Boys School. 2.06.2009. First Coast News.
BRUNSWICK, GA – Roger Kiser remembers it like it was yesterday. “Unless you were there. Unless you saw how out of control it was, nothing mattered, life didn’t matter.”
Kiser was at the Florida Reform School for Boys, now known as the Arthur Dozier School, back in the late 1950s.
He says at the school, there was a place called the “White House” where he was taken numerous times for beatings. “They beat you until you were bloody,” says Kiser.
According to a class action lawsuit filed against the state, a number of others who went to the school have the same memories.
Court records detail how during the beatings, employees placed, “…monetary bets (on who) could draw blood from the boys first.”
One boy remembers, “After the blood curdling screams of a boy stopped, one of the state employees was heard to state, ‘I think he is dead.’”
“I have heard…out of 86 men I’ve talked to, I’d say there are 30 who did not see boys return after their beating,” says Kiser.
More than 30 graves have been found near the school’s property. The state is now investigating who is buried there.
According to the lawsuit, the victims have an idea who beat and sexually abused them. Two former employees are named in the lawsuit. They are Troy Tidwell and Robert Curry.
“Troy Tidwell is a gentleman who has one arm,” says Kiser, who notes Tidwell was one of the worst beaters. “Robert Curry was the psychologist. He was one that was molesting a lot of the boys,” says Kiser.
Kiser also notes they know who the other abusers are but most have passed away.
Tidwell’s phone is no longer in service. His attorney was not available for comment. Kiser says his attorneys are still trying to find Curry.
According to the lawsuit, after beatings boys were, “Placed in a ‘hole’ which was an approximately eight by eight foot cell with no lights or windows.” It also goes on to say, “Boys would spend as many as 30 days (there to) cover up the severe nature of the beatings.”
“I never went there. I do know boys were beaten so badly their visitation rights were suspended until they could somewhat heal up,” says Kiser.
The lawsuit alleges the abuse happened between the 1940s and 1960s.
Kiser has written a book about his experience. He believes there could be hundreds of men out there who were abused at the school over the years. Right now, he says more than 120 men have come forward.
http://www.firstcoastnews.com/news/local/news-article.aspx?storyid=130779&catid=3
INSTITUTIONAL CHILD ABUSE http://www.thestraights.com/index.htm and
Texas Juvenile Centers http://rawstory.com/news/2008/Texas_DA_reveals_evidence_against_Cheney_1127.html
Duration : 0:9:0
by ADMIN on MAY 12, 2010
This is standard operating procedure in the U.S., hence all the raped, abused, and dead babies and toddlers laying around while in CPS custody/oversight, or adopted, or in juvenile “reform” centers – all havens for pedophiles. See links at bottom. — “The White House Boys” Trailer, the horrifying true story of a reform school in Mariana, Florida in the 1950s whose administrators raped, abused and killed young boys. After victims came forward demanding justice the Governor of Florida launched a mandatory investigation to uncover the truth behind the hundreds of unmarked graves located at the school. Families insisted that their lost children were buried there after being beaten to death in the White House. Based on the book “The White House Boys” by Roger Kiser. This is a sneak peak to the documentary and film presented to you by Franchesca Elder and Paul Hensler.
“White House Boys” Sue State Over Abuse at Florida State Boys School. 2.06.2009. First Coast News.
BRUNSWICK, GA – Roger Kiser remembers it like it was yesterday. “Unless you were there. Unless you saw how out of control it was, nothing mattered, life didn’t matter.”
Kiser was at the Florida Reform School for Boys, now known as the Arthur Dozier School, back in the late 1950s.
He says at the school, there was a place called the “White House” where he was taken numerous times for beatings. “They beat you until you were bloody,” says Kiser.
According to a class action lawsuit filed against the state, a number of others who went to the school have the same memories.
Court records detail how during the beatings, employees placed, “…monetary bets (on who) could draw blood from the boys first.”
One boy remembers, “After the blood curdling screams of a boy stopped, one of the state employees was heard to state, ‘I think he is dead.’”
“I have heard…out of 86 men I’ve talked to, I’d say there are 30 who did not see boys return after their beating,” says Kiser.
More than 30 graves have been found near the school’s property. The state is now investigating who is buried there.
According to the lawsuit, the victims have an idea who beat and sexually abused them. Two former employees are named in the lawsuit. They are Troy Tidwell and Robert Curry.
“Troy Tidwell is a gentleman who has one arm,” says Kiser, who notes Tidwell was one of the worst beaters. “Robert Curry was the psychologist. He was one that was molesting a lot of the boys,” says Kiser.
Kiser also notes they know who the other abusers are but most have passed away.
Tidwell’s phone is no longer in service. His attorney was not available for comment. Kiser says his attorneys are still trying to find Curry.
According to the lawsuit, after beatings boys were, “Placed in a ‘hole’ which was an approximately eight by eight foot cell with no lights or windows.” It also goes on to say, “Boys would spend as many as 30 days (there to) cover up the severe nature of the beatings.”
“I never went there. I do know boys were beaten so badly their visitation rights were suspended until they could somewhat heal up,” says Kiser.
The lawsuit alleges the abuse happened between the 1940s and 1960s.
Kiser has written a book about his experience. He believes there could be hundreds of men out there who were abused at the school over the years. Right now, he says more than 120 men have come forward.
http://www.firstcoastnews.com/news/local/news-article.aspx?storyid=130779&catid=3
INSTITUTIONAL CHILD ABUSE http://www.thestraights.com/index.htm and
Texas Juvenile Centers http://rawstory.com/news/2008/Texas_DA_reveals_evidence_against_Cheney_1127.html
Duration : 0:9:0
Foster Children Mistreated, Suit Against City Claims
Foster Children Mistreated, Suit Against City Claims
By A. G. SULZBERGER
Published: May 12, 2010
A federal lawsuit is seeking to bar New York City from allowing troubled foster-care children to be kept in psychiatric hospitals after doctors have recommended their release, a practice that routinely adds months to a hospitalization despite laws that require such children to be placed in the least restrictive environment possible.
The suit, filed on Wednesday in United States District Court in Brooklyn, claims that the practice means that children who no longer require hospitalization are being kept in locked quarters where they have limited access to schooling, family visits and even walks outside.
The suit also claims that the Administration for Children’s Services, which oversees the care of about 16,000 foster children in New York City, and its subcontractors have been “using certain psychiatric hospitals as if they are detention centers,” sending some children to hospitals for disciplinary reasons, like breaking curfew, running away or getting in fights, rather than for mental health reasons.
A spokeswoman for the city’s Corporation Counsel declined to comment on the suit, saying the city had not yet had a chance to review it.
The suit was filed by the Legal Aid Society on behalf of three unnamed foster-care children who are currently hospitalized despite doctors’ recommendations that they be released.
“Every day that it continues, plaintiffs’ extended, wrongful confinement in these institutions is causing them irreparable damage,” the lawsuit says.
One of the children, a 6-year-old boy identified as S. M. who was placed into foster care last year, was hospitalized in Westchester in January, after “misbehavior” in his foster home, according to the complaint. The boy, who was in kindergarten, has been ready for discharge since April 2.
Another child, a 13-year-old boy identified as M. M., remains hospitalized on Long Island, though he was recommended for discharge on Jan. 26.
Legal Aid, a nonprofit group that represents foster-care children in New York, is seeking a preliminary injunction ordering the release of the three children, as well as a court order prohibiting the city from continuing to place foster-care children in hospitals unless doing so is medically necessary, and requiring that less-restrictive placements are made available for any child ready for release within 24 hours. The lawsuit also seeks financial damages.
Legal Aid requested class-action status for the lawsuit and identified two dozen more cases in which it claimed that children were held inappropriately, Nancy Rosenbloom, one of the Legal Aid lawyers handling the case, said. There is a high incidence of mental illness among foster-care children, who have been separated from their families, many after suffering physical or sexual abuse, said Marcia Lowry, executive director of the advocacy group Children’s Rights.
The suit cited a study by the group that estimated that about 14 percent of the foster care children in New York had been admitted to a psychiatric hospital in the course of a single year. Under both state and federal law, the city is required to place the children in the “most homelike” environment.
But foster homes, group homes and residential treatment centers can be unable or unwilling to accept children with mental illness or severe behavioral problems. The city has a policy against transferring children discharged from psychiatric hospitals to its Children’s Center, which temporarily houses other children during transition periods, according to Legal Aid.
“Some of these kids do have serious mental-health needs that may require hospitalization,” Ms. Rosenbloom said. “But the point of this case is once they’re ready to get out, they should get out.”
http://www.nytimes.com/2010/05/13/nyregion/13acs.html?partner=rss&emc=rss
By A. G. SULZBERGER
Published: May 12, 2010
A federal lawsuit is seeking to bar New York City from allowing troubled foster-care children to be kept in psychiatric hospitals after doctors have recommended their release, a practice that routinely adds months to a hospitalization despite laws that require such children to be placed in the least restrictive environment possible.
The suit, filed on Wednesday in United States District Court in Brooklyn, claims that the practice means that children who no longer require hospitalization are being kept in locked quarters where they have limited access to schooling, family visits and even walks outside.
The suit also claims that the Administration for Children’s Services, which oversees the care of about 16,000 foster children in New York City, and its subcontractors have been “using certain psychiatric hospitals as if they are detention centers,” sending some children to hospitals for disciplinary reasons, like breaking curfew, running away or getting in fights, rather than for mental health reasons.
A spokeswoman for the city’s Corporation Counsel declined to comment on the suit, saying the city had not yet had a chance to review it.
The suit was filed by the Legal Aid Society on behalf of three unnamed foster-care children who are currently hospitalized despite doctors’ recommendations that they be released.
“Every day that it continues, plaintiffs’ extended, wrongful confinement in these institutions is causing them irreparable damage,” the lawsuit says.
One of the children, a 6-year-old boy identified as S. M. who was placed into foster care last year, was hospitalized in Westchester in January, after “misbehavior” in his foster home, according to the complaint. The boy, who was in kindergarten, has been ready for discharge since April 2.
Another child, a 13-year-old boy identified as M. M., remains hospitalized on Long Island, though he was recommended for discharge on Jan. 26.
Legal Aid, a nonprofit group that represents foster-care children in New York, is seeking a preliminary injunction ordering the release of the three children, as well as a court order prohibiting the city from continuing to place foster-care children in hospitals unless doing so is medically necessary, and requiring that less-restrictive placements are made available for any child ready for release within 24 hours. The lawsuit also seeks financial damages.
Legal Aid requested class-action status for the lawsuit and identified two dozen more cases in which it claimed that children were held inappropriately, Nancy Rosenbloom, one of the Legal Aid lawyers handling the case, said. There is a high incidence of mental illness among foster-care children, who have been separated from their families, many after suffering physical or sexual abuse, said Marcia Lowry, executive director of the advocacy group Children’s Rights.
The suit cited a study by the group that estimated that about 14 percent of the foster care children in New York had been admitted to a psychiatric hospital in the course of a single year. Under both state and federal law, the city is required to place the children in the “most homelike” environment.
But foster homes, group homes and residential treatment centers can be unable or unwilling to accept children with mental illness or severe behavioral problems. The city has a policy against transferring children discharged from psychiatric hospitals to its Children’s Center, which temporarily houses other children during transition periods, according to Legal Aid.
“Some of these kids do have serious mental-health needs that may require hospitalization,” Ms. Rosenbloom said. “But the point of this case is once they’re ready to get out, they should get out.”
http://www.nytimes.com/2010/05/13/nyregion/13acs.html?partner=rss&emc=rss
A License to Kill? Part 2: Who Guards Gardasil’s Guardians?
May 12, 2010
A License to Kill? Part 2: Who Guards Gardasil’s Guardians?
By Mark Blaxill
In the first part of this report (HERE), Age of Autism identified a pattern of conflict of interest at the Department of Health and Human Services (DHHS) involving Merck’s Gardasil vaccine. Researchers at the National Cancer Institute (NCI) invented critical technology for the “virus-like particles” (or VLPs) that were used in the Gardasil vaccine. As the invention reached the commercial marketplace, these researchers’ bosses at the National Institutes for Health (NIH) celebrated their work as “heroic” and “a journey we can learn from.” Meanwhile, officials in the NIH Office for Technology Transfer (OTT) filed for patents on the VLP technology invented at NCI, licensed those patent rights to vaccine manufacturers and eventually received royalties from Merck, Gardasil’s manufacturer, and GlaxoSmithKline (GSK).
In the second part of the series, Age of Autism will follow the Merck-DHHS “public-private partnership” as it moved beyond NIH to its sister agencies. In a subsequent process at the Food and Drug Administration (FDA), officials in the Center for Biologics Evaluation and Research (CBER) supervised the clinical trials and granted Merck the first “Biologics License Application” (BLA) for a human papillomavirus (HPV) vaccine. Three weeks later, the Advisory Committee on Immunization Practices (ACIP) of the Centers for Disease Control and Prevention (CDC) recommended universal HPV vaccination for women from nine to twenty-six years of age, guaranteeing in one series of votes that Gardasil would reach blockbuster status for Merck: annual revenues of well over $1 billion. Subsequently, agencies within FDA and CDC have been responsible for monitoring Gardasil’s safety in the field, as officials within the Health Resources Services Administration (HRSA) brace themselves to sit in judgment over a new wave of vaccine injury claims. As we pointed out in the first part of this series, this conflict of interest is both extraordinary in scope and poorly understood by the general public.
At the same time, simply observing the possibility of conflict between the commercial activities of NIH and the regulatory roles of other agencies doesn’t necessarily mean that there will be bias, negligence or lack of diligence on the part of DHHS regulators. Nevertheless, the proclamation of great victory for a vaccine against cervical cancer—one that prompted the NIH Director to single out the invention for praise to both Congress and the President and won its inventors recognition as Federal Employees of the Year—could certainly have created pressure to usher Gardasil through the BLA approval and ACIP recommendation processes with special attention and unusual dispatch. As a result, one might argue that the potential for bias on the part of CBER and ACIP regulators--regulators who would have had a dangerous temptation to relax their required skepticism and hold the favored new product to lower standards of safety—gave them a responsibility for unusual diligence and extra care. But what does the evidence really say about their actual level of diligence? Did CBER and ACIP officials betray their eagerness to enable the celebration of a new “anti-cancer vaccine” or did they hold Gardasil to even more exacting standards of safety? Let’s take a closer look at how FDA and CDC approached their respective responsibilities for Gardasil.
How stringent was FDA’s safety review for Gardasil?
When the FDA issued its approval of Merck’s BLA for Gardasil on June 8, 2006, its decision was based on a review of Merck’s data from five separate clinical trials, each of which included efficacy and safety assessments for Gardasil. Four of the five trials approached their efficacy and safety studies in similar fashion, comparing Gardasil against a “placebo” that contained an active ingredient, with one trial comparing Gardasil against what the CBER reviewers described as a “saline placebo.” All together, these five trials examined a total of close 12,000 subjects who received at least one dose of Gardasil and compared their outcomes to roughly 10,000 subjects who received up to three injections of what Merck and CBER officials agreed to describe as a “placebo.”
But what is a placebo, really? One definition describes a placebo as “an innocuous or inert medication; given as a pacifier or to the control group in experiments on the efficacy of a drug.” The operative term here is the word inert. But in four of the five trials, Gardasil placebos contained a substance called an adjuvant, “a substance which enhances the body's immune response to an antigen.” According to one of the trial publications, most of the Gardasil trial placebos actually contained an “amorphous aluminium hydroxyphosphate sulfate adjuvant… and was visually indistinguishable from vaccine.” So although the majority of the placebo treatments in the Gardasil trials did not include Gardasil VLPs, they were by no means inert. In control populations representing nearly 95% of all “placebo” recipients, the study subjects received a formulation that actually included an immunologically active (and potentially harmful) aluminum adjuvant.
One of the five trials, however, was different. In this trial, the only one that examined a younger population of nine-to-fifteen year olds, the placebo recipients did not receive an aluminum adjuvant. By contrast, and according to most of the FDA documentation, the nearly 600 control subjects in this trial received a formulation most commonly described as either a “non-alum placebo” or a “saline placebo.” The safety results of this trial deserve special notice, since it’s the only trial that compared Gardasil to a solution that could reasonably be described as “inert.”
But even that assumption would overstate the case. Although the “saline placebo” did contain water and sodium chloride (ordinary table salt), the FDA was incorrect to suggest that there were no other active ingredients. According to the published description of this trial’s methods, “The placebo used in this study contained identical components to those in the vaccine, with the exception of HPV L1 VLPs and aluminum adjuvant, in a total carrier volume of 0.5 mL.” Formulations like this, which are made up of everything in the vaccine except its immunologically active components, are sometimes called a “carrier solution.” The correct description of the placebo as a “carrier solution” rather than a “saline placebo” was provided only once in the CBER review, buried in a table on page 301. Nowhere in either the CBER review or the published account of the trial can one find any description of this placebo’s ingredients.
It is possible, however, to infer the composition of the carrier solution from Merck’s Gardasil package insert, which lists the vaccine’s immunologically inactive ingredients. These include: “yeast protein, sodium chloride [table salt], L-histidine [an amino acid], polysorbate 80 [an emulsifier], sodium borate, and water for injection.” At least one of these chemicals, sodium borate, is a chemically reactive toxin, one that has many industrial uses as an active ingredient. These include applications as: a replacement for mercury in gold mining; an insecticide and fungicide; and a food additive that is now banned in the United States.
Is there any defense for the FDA to allow this approach to placebo selection in the Gardasil trials? From an efficacy standpoint, one can reasonably argue that yes, using an adjuvant in a placebo makes sense, since it will provide the most rigorous test of the value of the active ingredient under review, in this case the VLPs invented at NCI. And in fact, the returns from all five clinical trials provided convincing evidence that when the VLPs were added to a vaccine formulation containing the aluminum adjuvant, a strong immune response resulted. CBER therefore drew the reasonable conclusion that Gardasil works, at least against the endpoints it was able to measure.
But is it safe? When it comes to the accurate measurement of adverse effects of Gardasil, there is little justification for reliance on a placebo with ingredients that are not inert. There is some limited value, perhaps, in comparing adverse events that are introduced solely by the addition of VLPs to the vaccine solution. But a truly rigorous safety assessment would investigate the full safety profile of the VLPs in combination with the aluminum adjuvant and compare that profile to the profile of an inert solution. After all, the adjuvant is present precisely because it is not inert.
If the FDA trial standards were truly to enforce a high standard of safety, they would require the comparison of Gardasil’s safety profile to a true saline placebo. But Merck performed no such analysis and CBER permitted them to apply a lesser safety standard of safety analysis. As a result, CBER issued its BLA approval without any idea whatsoever of the true risks of Gardasil. Not surprisingly, most of the comparisons between adverse outcomes for those receiving doses of Gardasil and those exposed to an aluminum adjuvant “placebo” showed little evidence of injury risk from Gardasil.
Unfortunately, the conclusion that Gardasil was therefore safe was horribly wrong.
A different view of the Gardasil trial data
Based on the data provided in CBER’s review of the Gardasil trials, it is possible to piece together an alternative view of Gardasil’s adverse event profile by examining three separate populations: 1) the subjects who received actual doses of Gardasil (over 96% got all three doses); 2) the subjects who received a “placebo” containing an aluminum adjuvant (over 98% got 225 micrograms of amorphous aluminum hydroxide sulfate) formulated in a carrier solution that made it visually indistinguishable from the full vaccine; and 3) the subjects who received only doses of a carrier solution. For the Gardasil and aluminum adjuvant groups, safety results were collected in two ways: a smaller set of reported outcomes was measured for the entire trial group (the “general safety population”) and a smaller group (the “detailed safety population”), including the entire carrier solution group, followed a more detailed protocol. The respective sizes of these safety assessment groups are shown below. Unfortunately, the small relative size and somewhat unmatched profile of the carrier solution group reduces the statistical power of a comparative analysis across the three groups: the age profile of this carrier solution trial was younger (9-15 years of age) than the other four trials (10-26 years of age, with the bulk falling between 16-23 years old); and less female (54%) than the Gardasil recipients (over 90%) and the aluminum adjuvant recipients (100% female). Nevertheless, the results of this three way comparison are the closest thing we have to a valid, non-passive safety analysis; and they show striking differences in safety profiles, none of which can be attributed to sample bias.
There are several ways in which the CBER trial review permits a comparative safety analysis across all three groups. The first is by comparing immediate adverse events at the injection site: events such as pain, swelling, “erythema” (redness of the skin), hemorrhage and pruritis (itching). These events are highly specific and show up in the first few days; they can, however, vary quite a bit in terms of severity. The Gardasil trials reported their results for these injection site adverse events in the “detailed study population” within five days after any vaccination visit. The comparison of these outcomes is shown below (using a scale that keeps the ratios between the rates of the adverse events constant).
As the chart shows, the vast majority of the Gardasil (81%) and aluminum adjuvant (75%) groups reported some kind of adverse event, most of which involved some kind of pain. By contrast, less than half of the carrier solution group (45%) reported an adverse event. This pattern continues in almost all of the individual categories, with the Gardasil group showing the largest rate of local reactions, followed closely by the aluminum adjuvant group and then with a clear drop off in the frequency of adverse events in the carrier solution group. On a retrospective basis, all but one of the reduced risks for the carrier solution group were statistically significant.
The most striking difference between the three groups is in the area of “serious adverse events.” Although less frequent than minor instances of pain or swelling at the injection site, these serious events were disturbingly common in the groups exposed to active substances. Nearly 5% of the Gardasil recipients had a serious adverse event, well over six times the rate of the carrier solution group. And more than 2% of the aluminum “placebo” recipients had severe reactions, more than three times the rate of adverse events in the carrier solution group. Based on this finding alone, it’s hard to defend the choice to classify Merck’s adjuvant as an “inert” placebo.
A second approach to comparative safety analysis involves examining the adverse events that caused the participants to withdraw from the trial in a two week period after any vaccine visit. These withdrawals included a range of adverse reactions, only a small fraction of which the investigators designated as “severe.” But sudden deaths (which need not be specific to the vaccine) were also included. The comparison of the discontinuation rates in the three groups is shown below.
Overall, the rate of discontinuation was low, at less than half a percent. But in the carrier solution group not a single recipient chose to drop out of the trial. In addition, there were three discontinuations after two weeks due to deaths in the Gardasil group and one such death in the aluminum adjuvant groups, whereas there were zero deaths at any point in the carrier solution group. Seven discontinuations (four in the Gardasil group and three in the aluminum adjuvant group) were due to other severe adverse events. These are obviously small numbers, and the deaths were dismissed by the reviewers as unrelated to vaccination. And in fact, the rate of discontinuation in the Gardasil and aluminum adjuvant groups was nearly identical. As a result of this similarity on outcomes, the CBER reviewers dismissed any effect of vaccination on withdrawal decisions, in all likelihood because the vast majority of the officially designated “placebo” group was exposed to the aluminum adjuvant.
A third approach to a comparative safety analysis takes a longer view of adverse events, using data for serious adverse events over a twelve month period after the beginning of the trial. The FDA review includes voluminous data on these events, but one of the easiest to measure is simply the overall rate of serious adverse events. The trial data show rates for such serious events that were similar between the Gardasil and placebo group. Indeed the rate of serious adverse events in the Gardasil group (1%) was actually lower than the placebo group as a whole (1.1%). Not surprisingly, however, this result was driven entirely by a high rate of serious adverse events in the aluminum adjuvant group. When one examines the rate of serious adverse events in two distinct placebo groups, the rate of serious adverse events in the aluminum adjuvant group rises even higher, to 1.27%, while the rate in the carrier solution group comes out at zero. This comparison is shown below.
A final approach to safety assessment takes the extensive twelve-month data on the medical conditions in all trial subjects and examines the longer term adverse events in specific categories of interest. Several such categories show disturbing patterns. Autoimmune conditions like arthritis, lupus and thyroiditis were sharply higher in the Gardasil group when compared to the overall “placebo” group and were even noted by the FDA reviewer as a source of concern. These occurred at a rate of over 1 in 1000 in the Gardasil group; there were, however, zero reported cases of autoimmune disorders in the carrier solution group. As in the two week analysis, death rates over twelve months were higher in the Gardasil and aluminum groups. By contrast, the carrier solution group had no deaths in the longer period. The chart below shows the results for the twelve month analysis.
How much of the low rate of adverse events in the carrier solution group (officially designated the “018 Protocol”) was due not to real differences in outcome but rather to sample bias, the fact that the population for the 018 Protocol was younger and less purely female than the other four trial populations? The short answer is, not very much. There are several ways to test the effect of sample bias. These include: comparing the adverse event rate in the 018 Gardasil group to the Gardasil groups in the other four protocols (higher adverse events show the 018 population was more vulnerable); comparing differences in adverse event rates between boys and girls in the 018 Gardasil group (higher adverse events in boys also show the 018 population was more vulnerable); and comparing differences in rates between the 9-12 year olds and the 13-15 year olds in the 018 Gardasil groups (higher adverse events in younger subjects show the 018 group was more vulnerable). If anything, most of these comparisons suggest the use of the carrier solution group understates the adverse event rate for Gardasil. For example, the younger subjects in both 018 groups had a higher rate of injection site adverse events and the 018 Gardasil group also had a higher rate of severe adverse events than the other groups. Only the findings on deaths and discontinuations (which were most frequent in the Protocol 018 Gardasil boys and 13-15 year olds) might have been influenced by sample bias.
The FDA downplayed deaths during the clinical trial
When it came to the most serious adverse event of all, death, the FDA review effectively gave Gardasil a free pass. They failed to mention, of course, that the deaths in their “placebo” group actually received the entirety of the vaccine’s contents excepting the VLPs. Nevertheless, they did report briefly on each individual case of death. In cases of death due to traumatic events like motor vehicle accidents, however, no details were reported (could a seizure or heart attack while driving have caused some traumatic events?). In most of the biologically-related deaths, they found reasons not to make any connection to Gardasil or to blame the victims’ behavior (“they were on birth control pills”) or family history (“the family had a history of arrhythmia”). Here is the FDA reviewer’s summary of the deaths in the trial.
There were 10 deaths in the Gardasil recipients (0.8%), and 7 deaths in the placebo group (0.7%). The majority of the deaths were due to trauma in both groups. These deaths did not appear related to vaccine administration.
In each treatment group, there was a death related to a deep vein thrombosis and/or pulmonary embolism, and both subjects were on hormonal contraceptives. The Gardasil recipient with this event had symptoms of leg pain prior to the first vaccination. The other Gardasil recipients who died included one subject with pancreatic cancer 578 days after dose 3, and one young male who died of arrhythmia 27 days after dose 1. This latter subject had a strong family history for arrhythmia. These events did not appear related to administration of the vaccine.
Even if all of these deaths could be explained away one way or another, this certainly sounds like a lot of deaths for such a young, and overwhelmingly female, group (16 of the 17 deaths were in females; one 15 year-old male Gardasil recipient died of a heart attack). What kind of death rate is normal for young women? The trials provide no such reference rate, but such statistics are readily available. Carnegie Mellon has a web-site called “Death Risk Rankings” (see HERE) that provides an interactive tool for calculating death rates within a wide range of demographic categories. For American females in the age range of the Gardasil trials (9-26 years of age), the rates are as follows: 2.75 per 10,000 in 10-19 year olds and 5.03 per 10,000 in 20-29 year olds. [Note: the majority of trial subjects were from the U.S. and Europe. European deaths rates from young women are 30% lower than American death rates, making this a conservative comparison].
Out of 11,778 Gardasil recipients, over 90% of them young women between the ages of 9 and 23, one would expect an annual death rate to be a mix of the rates for the two reference groups, or less than 4 per 10,000 in an entire year. But in the trials, there were three “sudden deaths”, i.e. deaths that occurred within just the two weeks of the Gardasil injections, in a review period of less than forty-five days. That’s a death rate close to ten times higher than would be expected such a short period. And the overall Gardasil death rate of 8.5 per 10,000 (10 deaths out of 11,778) for the 12 month period of the trial is more than twice what one would expect. The FDA review evinced little concern over this high death rate, preferring instead to compare the deaths in the Gardasil group to that of the “placebo” group. But as one can see from the chart below, the death rate in the aluminum adjuvant group was higher than the reference groups as well.
In short, the CBER review of Gardasil condoned the use of an immunologically active placebo and not an inert solution. So instead of a adopting an increased measure of diligence in light of the potential for bias due to the DHHS conflict of interest in Gardasil, it appears that FDA permitted Merck to use a lower standard of safety. Only by using the single set of trial data in which the placebo solution was relatively (although not entirely) inert, can one assess the impact of this relaxed standard. Based on an analysis of this data, one is drawn to an inescapable conclusion.
Gardasil was not safe.
ACIP’s recommendation for universal vaccination of young females
If the FDA was less than diligent in its review of safety profile of the anti-cancer vaccine invented at its sister agency at NIH, how did its counterparts at CDC compare in terms of their own decision processes? Faced with a choice either to take a deliberate course, allowing a period of observation to follow Gardasil’s BLA approval, or to rush Gardasil into widespread use, CDC’s approach provides another standard of comparison for DHHS’s conduct. Would their key decision-making group, the Advisory Committee on Immunization Practices (ACIP) choose the deliberate or the hasty path?
There is very little ambiguity in this answer. ACIP wasted absolutely no time in recommending Gardasil for universal use among young women. Indeed, it would have been hard for them to move any faster. In June 2006, almost immediately after FDA approval, ACIP recommended the HPV vaccination. An account in the March 23, 2007 edition of the CDC publication, Morbidity and Mortality Weekly Report (MMWR) showed that ACIP was preparing for near instantaneous approval even before the FDA’s final reviews were completed.
The Advisory Committee on Immunization Practices (ACIP) HPV vaccine workgroup first met in February 2004 to begin reviewing data related to the quadrivalent HPV vaccine. The workgroup held monthly teleconferences and meetings three times a year to review published and unpublished data from the HPV vaccine clinical trials, including data on safety, immunogenicity, and efficacy. Data on epidemiology and natural history of HPV, vaccine acceptability, and sexual behavior in the United States also were reviewed. Several economic and cost effectiveness analyses were considered. Presentations on these topics were made to ACIP during meetings in June 2005, October 2005, and February 2006. Recommendation options were developed and discussed by the ACIP HPV vaccine workgroup. When evidence was lacking, the recommendations incorporated expert opinion of the workgroup members. Options being considered by the workgroup were presented to ACIP in February 2006. The final recommendations were presented to ACIP at the June 2006 ACIP meeting. After discussions, minor modifications were made and the recommendations were approved at the June 2006 meeting.
The date of the BLA approval for Gardasil was June 6, 2006. In the June 29 ACIP meeting, just 23 days after the FDA’s decision, ACIP gave Gardasil its formal support. The vote was unanimous, with two of the fifteen members abstaining due to their financial involvements with Merck.
But not only was the vote unanimous, the mood in the meeting was celebratory. Numerous vaccine safety advocates attended the June meeting due to their concerns over the influenza vaccines. One attendee recounted the reaction to the Gardasil decision. “After the vote the place erupted in applause. There was hand-shaking and back-slapping. It seemed kind of odd and inappropriate to us.” Asked why it seemed inappropriate, the observer explained that the concern arose, “because they were so clearly cheering the recommendation. It was clear and absolutely a celebratory reaction.”
The safety discussion was almost exclusively informed, of course, by the FDA’s flawed trial data. Not surprisingly, few concerns were raised. Here’s what the ACIP minutes had to say about Gardasil’s safety profile.
The clinical trial program places strong emphasis on evaluating the safety profile of GARDASIL®. Of ~21,464 subjects, ~11,000 received detailed safety follow-up and the remainder received serious adverse experiences in medical history and pregnancy follow-up. The incidence of overall adverse events (AEs), injection-site AEs, and low-grade fevers >100°F was slightly higher in the GARDASIL® group compared to the placebo group. Systemic AEs were comparable between the two groups. Serious AEs and discontinuation due to adverse experiences were extremely rare. [emphasis added]
As a result of this accelerated process, ACIP made a series of recommendations. The first placed Gardasil on the recommended list of childhood vaccines. “ACIP recommends routine vaccination of females 11-12 years of age, with three doses of the quadrivalent HPV vaccine. The vaccine series can be started as young as nine years of age at the discretion of the provider.” In the context of the clinical trials, this was an extremely aggressive recommendation. A scant 85 pre-pubescent girls, nine years of age or younger had received Gardasil in any trial (matched with only 48 controls) and only three percent of the Gardasil trail recipients were in the range of ACIP’s target population of 11-12 year olds. Not only was ACIP basing its recommendation on flawed safety analysis, it was extending its recommendations to include groups who lay outside of even this biased assessment.
But ACIP didn’t stop there. They also recommended a catch-up vaccine for all young women, even those who would have been sexually active for many years, who had contracted at least one strain of the virus, cleared it, and therefore received diminished benefit from vaccination. “ACIP recommends vaccination for females 13-26 years of age who have not been previously vaccinated. Ideally, vaccine should be administered before onset of sexual activity, but females who are sexually active should still be vaccinated.” From a commercial perspective, this recommendation multiplied Gardasil’s profit potential for Merck and its NIH partners, creating a near term target market that was seven times larger than just the routine market of 11-12 year- olds.
There was little effective restriction placed on Gardasil’s market potential. And only the yeast protein in the carrier solution was cited as a safety concern. “Vaccination should be deferred until after moderate or severe acute illnesses improve,” read the ACIP recommendation. “A history of hypersensitivity or severe allergic reaction to yeast or any other vaccine component should be classified as a contraindication. Initiation of the vaccine series should be delayed until after completion of the pregnancy.”
The momentum for an aggressive roll-out was strong. Representatives from nine different organizations gave formal statements in support of Gardasil during the public comment period. In the meantime, and with a strong push from Merck, some state officials stood in line to move even faster than ACIP. In February of 2007, Republican Texas Gov. Rick Perry bypassed the legislature and mandated Gardasil for all 11- and 12-year-old girls in the state.
The commercial results were powerful and immediate. Merck reported its first revenues from Gardasil in the second quarter of 2006 (presumably from sales after the June BLA approval), and its revenues began to climb rapidly: $70 million in the third quarter, $155 million in the fourth quarter, all leading to a blockbuster year of 2007 in which Gardasil recorded revenues of $1.5 billion. The financial bonanza had begun in earnest.
A few years later, Merck would attract criticism for its aggressive marketing of Gardasil during this period. Sheila and David Rothman wrote a sharp critique in the Journal of the American Medical Association (hardly a radical hotbed of vaccine consumerism) in which they neglected the conflicts described here but noted the extreme measures that Merck adopted.
The marketing of this vaccine broke with traditional practices. Heretofore, vaccines had been identified by the disease they were preventing (measles, mumps) or by their creators (Salk or Sabin). This HPV vaccine followed a different model. It was identified by a trade name, Gardasil, and promoted primarily to “guard” not against HPV viruses or sexually transmitted diseases but against cervical cancer. The marketing campaign that followed, according to Merck’s chief executive officer, proceeded “flawlessly.” In 2006, Gardasil was named the pharmaceutical “brand of the year” for building “a market out of thin air.”
But the Rothmans’ critique would do little to delay or disrupt the launch. At the time of the DHHS rush to market there were few dissenting voices and none of them were heard at ACIP.
One lone voice stood out. In March 2007, just as the vaccine was reaching its peak revenue numbers, one of the doctors who had guided the clinical trials voiced an objection. On March 14, 2007, an article in a small newspaper in Fort Wayne, Indiana reported on an interview with one of the scientists involved in the clinical trials. The scientist was named Diane Harper and she expressed dismay at the ACIP recommendation.
"Giving it to 11-year-olds is a great big public health experiment," said Diane M. Harper, who is a scientist, physician, professor and the director of the Gynecologic Cancer Prevention Research Group at the Norris Cotton Cancer Center at Dartmouth Medical School in New Hampshire.
"It is silly to mandate vaccination of 11- to 12-year-old girls There also is not enough evidence gathered on side effects to know that safety is not an issue."
Harper didn’t have much to gain from the commercial success of Gardasil, but she also was taking considerable risks by breaking ranks with her colleagues. One can only imagine how things would have been different if she had been in charge of the review process at FDA rather than running one branch of the clinical trial. In the midst of such a widespread degradation in regulatory ethics and standards, it’s interesting to consider why she made that choice.
The Fort Wayne reporter, Cindy Bevington, was frank as to why Harper was telling her story to them rather than a larger media outlet. “For months, Harper said, she's been trying to convince major television and print media to listen to her and tell the facts about the usefulness and effectiveness of this vaccine.” Why was an inside critique of the Gardasil promotion campaign not already big news? "No one will print it," Harper said.
Over the coming months, the assessment of adverse effects of Gardasil would be transferred to a different group within DHHS, from CBER and ACIP to the “postlicensure safety surveillance” groups within FDA and CDC. At this point, the deaths and serious adverse events would leave the realm of closely held statistics within a vaccine manufacturer’s actively monitored trial sample and into the realm of passive surveillance in the general population; soon watchdog and vaccine safety groups like National Vaccine Information Center and Judicial Watch issued critical analyses, see HERE and HERE. And Harper’s concerns over the inadequate safety data would prove prophetic. Why had Harper broken ranks so early? When Bevington asked Harper why she was speaking out despite the momentum to the contrary, her answer was refreshingly simple.
“I want to be able to sleep with myself when I go to bed at night.”
http://www.ageofautism.com/2010/05/a-license-to-kill-part-2-who-guards-gardasils-guardians.html
A License to Kill? Part 2: Who Guards Gardasil’s Guardians?
By Mark Blaxill
In the first part of this report (HERE), Age of Autism identified a pattern of conflict of interest at the Department of Health and Human Services (DHHS) involving Merck’s Gardasil vaccine. Researchers at the National Cancer Institute (NCI) invented critical technology for the “virus-like particles” (or VLPs) that were used in the Gardasil vaccine. As the invention reached the commercial marketplace, these researchers’ bosses at the National Institutes for Health (NIH) celebrated their work as “heroic” and “a journey we can learn from.” Meanwhile, officials in the NIH Office for Technology Transfer (OTT) filed for patents on the VLP technology invented at NCI, licensed those patent rights to vaccine manufacturers and eventually received royalties from Merck, Gardasil’s manufacturer, and GlaxoSmithKline (GSK).
In the second part of the series, Age of Autism will follow the Merck-DHHS “public-private partnership” as it moved beyond NIH to its sister agencies. In a subsequent process at the Food and Drug Administration (FDA), officials in the Center for Biologics Evaluation and Research (CBER) supervised the clinical trials and granted Merck the first “Biologics License Application” (BLA) for a human papillomavirus (HPV) vaccine. Three weeks later, the Advisory Committee on Immunization Practices (ACIP) of the Centers for Disease Control and Prevention (CDC) recommended universal HPV vaccination for women from nine to twenty-six years of age, guaranteeing in one series of votes that Gardasil would reach blockbuster status for Merck: annual revenues of well over $1 billion. Subsequently, agencies within FDA and CDC have been responsible for monitoring Gardasil’s safety in the field, as officials within the Health Resources Services Administration (HRSA) brace themselves to sit in judgment over a new wave of vaccine injury claims. As we pointed out in the first part of this series, this conflict of interest is both extraordinary in scope and poorly understood by the general public.
At the same time, simply observing the possibility of conflict between the commercial activities of NIH and the regulatory roles of other agencies doesn’t necessarily mean that there will be bias, negligence or lack of diligence on the part of DHHS regulators. Nevertheless, the proclamation of great victory for a vaccine against cervical cancer—one that prompted the NIH Director to single out the invention for praise to both Congress and the President and won its inventors recognition as Federal Employees of the Year—could certainly have created pressure to usher Gardasil through the BLA approval and ACIP recommendation processes with special attention and unusual dispatch. As a result, one might argue that the potential for bias on the part of CBER and ACIP regulators--regulators who would have had a dangerous temptation to relax their required skepticism and hold the favored new product to lower standards of safety—gave them a responsibility for unusual diligence and extra care. But what does the evidence really say about their actual level of diligence? Did CBER and ACIP officials betray their eagerness to enable the celebration of a new “anti-cancer vaccine” or did they hold Gardasil to even more exacting standards of safety? Let’s take a closer look at how FDA and CDC approached their respective responsibilities for Gardasil.
How stringent was FDA’s safety review for Gardasil?
When the FDA issued its approval of Merck’s BLA for Gardasil on June 8, 2006, its decision was based on a review of Merck’s data from five separate clinical trials, each of which included efficacy and safety assessments for Gardasil. Four of the five trials approached their efficacy and safety studies in similar fashion, comparing Gardasil against a “placebo” that contained an active ingredient, with one trial comparing Gardasil against what the CBER reviewers described as a “saline placebo.” All together, these five trials examined a total of close 12,000 subjects who received at least one dose of Gardasil and compared their outcomes to roughly 10,000 subjects who received up to three injections of what Merck and CBER officials agreed to describe as a “placebo.”
But what is a placebo, really? One definition describes a placebo as “an innocuous or inert medication; given as a pacifier or to the control group in experiments on the efficacy of a drug.” The operative term here is the word inert. But in four of the five trials, Gardasil placebos contained a substance called an adjuvant, “a substance which enhances the body's immune response to an antigen.” According to one of the trial publications, most of the Gardasil trial placebos actually contained an “amorphous aluminium hydroxyphosphate sulfate adjuvant… and was visually indistinguishable from vaccine.” So although the majority of the placebo treatments in the Gardasil trials did not include Gardasil VLPs, they were by no means inert. In control populations representing nearly 95% of all “placebo” recipients, the study subjects received a formulation that actually included an immunologically active (and potentially harmful) aluminum adjuvant.
One of the five trials, however, was different. In this trial, the only one that examined a younger population of nine-to-fifteen year olds, the placebo recipients did not receive an aluminum adjuvant. By contrast, and according to most of the FDA documentation, the nearly 600 control subjects in this trial received a formulation most commonly described as either a “non-alum placebo” or a “saline placebo.” The safety results of this trial deserve special notice, since it’s the only trial that compared Gardasil to a solution that could reasonably be described as “inert.”
But even that assumption would overstate the case. Although the “saline placebo” did contain water and sodium chloride (ordinary table salt), the FDA was incorrect to suggest that there were no other active ingredients. According to the published description of this trial’s methods, “The placebo used in this study contained identical components to those in the vaccine, with the exception of HPV L1 VLPs and aluminum adjuvant, in a total carrier volume of 0.5 mL.” Formulations like this, which are made up of everything in the vaccine except its immunologically active components, are sometimes called a “carrier solution.” The correct description of the placebo as a “carrier solution” rather than a “saline placebo” was provided only once in the CBER review, buried in a table on page 301. Nowhere in either the CBER review or the published account of the trial can one find any description of this placebo’s ingredients.
It is possible, however, to infer the composition of the carrier solution from Merck’s Gardasil package insert, which lists the vaccine’s immunologically inactive ingredients. These include: “yeast protein, sodium chloride [table salt], L-histidine [an amino acid], polysorbate 80 [an emulsifier], sodium borate, and water for injection.” At least one of these chemicals, sodium borate, is a chemically reactive toxin, one that has many industrial uses as an active ingredient. These include applications as: a replacement for mercury in gold mining; an insecticide and fungicide; and a food additive that is now banned in the United States.
Is there any defense for the FDA to allow this approach to placebo selection in the Gardasil trials? From an efficacy standpoint, one can reasonably argue that yes, using an adjuvant in a placebo makes sense, since it will provide the most rigorous test of the value of the active ingredient under review, in this case the VLPs invented at NCI. And in fact, the returns from all five clinical trials provided convincing evidence that when the VLPs were added to a vaccine formulation containing the aluminum adjuvant, a strong immune response resulted. CBER therefore drew the reasonable conclusion that Gardasil works, at least against the endpoints it was able to measure.
But is it safe? When it comes to the accurate measurement of adverse effects of Gardasil, there is little justification for reliance on a placebo with ingredients that are not inert. There is some limited value, perhaps, in comparing adverse events that are introduced solely by the addition of VLPs to the vaccine solution. But a truly rigorous safety assessment would investigate the full safety profile of the VLPs in combination with the aluminum adjuvant and compare that profile to the profile of an inert solution. After all, the adjuvant is present precisely because it is not inert.
If the FDA trial standards were truly to enforce a high standard of safety, they would require the comparison of Gardasil’s safety profile to a true saline placebo. But Merck performed no such analysis and CBER permitted them to apply a lesser safety standard of safety analysis. As a result, CBER issued its BLA approval without any idea whatsoever of the true risks of Gardasil. Not surprisingly, most of the comparisons between adverse outcomes for those receiving doses of Gardasil and those exposed to an aluminum adjuvant “placebo” showed little evidence of injury risk from Gardasil.
Unfortunately, the conclusion that Gardasil was therefore safe was horribly wrong.
A different view of the Gardasil trial data
Based on the data provided in CBER’s review of the Gardasil trials, it is possible to piece together an alternative view of Gardasil’s adverse event profile by examining three separate populations: 1) the subjects who received actual doses of Gardasil (over 96% got all three doses); 2) the subjects who received a “placebo” containing an aluminum adjuvant (over 98% got 225 micrograms of amorphous aluminum hydroxide sulfate) formulated in a carrier solution that made it visually indistinguishable from the full vaccine; and 3) the subjects who received only doses of a carrier solution. For the Gardasil and aluminum adjuvant groups, safety results were collected in two ways: a smaller set of reported outcomes was measured for the entire trial group (the “general safety population”) and a smaller group (the “detailed safety population”), including the entire carrier solution group, followed a more detailed protocol. The respective sizes of these safety assessment groups are shown below. Unfortunately, the small relative size and somewhat unmatched profile of the carrier solution group reduces the statistical power of a comparative analysis across the three groups: the age profile of this carrier solution trial was younger (9-15 years of age) than the other four trials (10-26 years of age, with the bulk falling between 16-23 years old); and less female (54%) than the Gardasil recipients (over 90%) and the aluminum adjuvant recipients (100% female). Nevertheless, the results of this three way comparison are the closest thing we have to a valid, non-passive safety analysis; and they show striking differences in safety profiles, none of which can be attributed to sample bias.
There are several ways in which the CBER trial review permits a comparative safety analysis across all three groups. The first is by comparing immediate adverse events at the injection site: events such as pain, swelling, “erythema” (redness of the skin), hemorrhage and pruritis (itching). These events are highly specific and show up in the first few days; they can, however, vary quite a bit in terms of severity. The Gardasil trials reported their results for these injection site adverse events in the “detailed study population” within five days after any vaccination visit. The comparison of these outcomes is shown below (using a scale that keeps the ratios between the rates of the adverse events constant).
As the chart shows, the vast majority of the Gardasil (81%) and aluminum adjuvant (75%) groups reported some kind of adverse event, most of which involved some kind of pain. By contrast, less than half of the carrier solution group (45%) reported an adverse event. This pattern continues in almost all of the individual categories, with the Gardasil group showing the largest rate of local reactions, followed closely by the aluminum adjuvant group and then with a clear drop off in the frequency of adverse events in the carrier solution group. On a retrospective basis, all but one of the reduced risks for the carrier solution group were statistically significant.
The most striking difference between the three groups is in the area of “serious adverse events.” Although less frequent than minor instances of pain or swelling at the injection site, these serious events were disturbingly common in the groups exposed to active substances. Nearly 5% of the Gardasil recipients had a serious adverse event, well over six times the rate of the carrier solution group. And more than 2% of the aluminum “placebo” recipients had severe reactions, more than three times the rate of adverse events in the carrier solution group. Based on this finding alone, it’s hard to defend the choice to classify Merck’s adjuvant as an “inert” placebo.
A second approach to comparative safety analysis involves examining the adverse events that caused the participants to withdraw from the trial in a two week period after any vaccine visit. These withdrawals included a range of adverse reactions, only a small fraction of which the investigators designated as “severe.” But sudden deaths (which need not be specific to the vaccine) were also included. The comparison of the discontinuation rates in the three groups is shown below.
Overall, the rate of discontinuation was low, at less than half a percent. But in the carrier solution group not a single recipient chose to drop out of the trial. In addition, there were three discontinuations after two weeks due to deaths in the Gardasil group and one such death in the aluminum adjuvant groups, whereas there were zero deaths at any point in the carrier solution group. Seven discontinuations (four in the Gardasil group and three in the aluminum adjuvant group) were due to other severe adverse events. These are obviously small numbers, and the deaths were dismissed by the reviewers as unrelated to vaccination. And in fact, the rate of discontinuation in the Gardasil and aluminum adjuvant groups was nearly identical. As a result of this similarity on outcomes, the CBER reviewers dismissed any effect of vaccination on withdrawal decisions, in all likelihood because the vast majority of the officially designated “placebo” group was exposed to the aluminum adjuvant.
A third approach to a comparative safety analysis takes a longer view of adverse events, using data for serious adverse events over a twelve month period after the beginning of the trial. The FDA review includes voluminous data on these events, but one of the easiest to measure is simply the overall rate of serious adverse events. The trial data show rates for such serious events that were similar between the Gardasil and placebo group. Indeed the rate of serious adverse events in the Gardasil group (1%) was actually lower than the placebo group as a whole (1.1%). Not surprisingly, however, this result was driven entirely by a high rate of serious adverse events in the aluminum adjuvant group. When one examines the rate of serious adverse events in two distinct placebo groups, the rate of serious adverse events in the aluminum adjuvant group rises even higher, to 1.27%, while the rate in the carrier solution group comes out at zero. This comparison is shown below.
A final approach to safety assessment takes the extensive twelve-month data on the medical conditions in all trial subjects and examines the longer term adverse events in specific categories of interest. Several such categories show disturbing patterns. Autoimmune conditions like arthritis, lupus and thyroiditis were sharply higher in the Gardasil group when compared to the overall “placebo” group and were even noted by the FDA reviewer as a source of concern. These occurred at a rate of over 1 in 1000 in the Gardasil group; there were, however, zero reported cases of autoimmune disorders in the carrier solution group. As in the two week analysis, death rates over twelve months were higher in the Gardasil and aluminum groups. By contrast, the carrier solution group had no deaths in the longer period. The chart below shows the results for the twelve month analysis.
How much of the low rate of adverse events in the carrier solution group (officially designated the “018 Protocol”) was due not to real differences in outcome but rather to sample bias, the fact that the population for the 018 Protocol was younger and less purely female than the other four trial populations? The short answer is, not very much. There are several ways to test the effect of sample bias. These include: comparing the adverse event rate in the 018 Gardasil group to the Gardasil groups in the other four protocols (higher adverse events show the 018 population was more vulnerable); comparing differences in adverse event rates between boys and girls in the 018 Gardasil group (higher adverse events in boys also show the 018 population was more vulnerable); and comparing differences in rates between the 9-12 year olds and the 13-15 year olds in the 018 Gardasil groups (higher adverse events in younger subjects show the 018 group was more vulnerable). If anything, most of these comparisons suggest the use of the carrier solution group understates the adverse event rate for Gardasil. For example, the younger subjects in both 018 groups had a higher rate of injection site adverse events and the 018 Gardasil group also had a higher rate of severe adverse events than the other groups. Only the findings on deaths and discontinuations (which were most frequent in the Protocol 018 Gardasil boys and 13-15 year olds) might have been influenced by sample bias.
The FDA downplayed deaths during the clinical trial
When it came to the most serious adverse event of all, death, the FDA review effectively gave Gardasil a free pass. They failed to mention, of course, that the deaths in their “placebo” group actually received the entirety of the vaccine’s contents excepting the VLPs. Nevertheless, they did report briefly on each individual case of death. In cases of death due to traumatic events like motor vehicle accidents, however, no details were reported (could a seizure or heart attack while driving have caused some traumatic events?). In most of the biologically-related deaths, they found reasons not to make any connection to Gardasil or to blame the victims’ behavior (“they were on birth control pills”) or family history (“the family had a history of arrhythmia”). Here is the FDA reviewer’s summary of the deaths in the trial.
There were 10 deaths in the Gardasil recipients (0.8%), and 7 deaths in the placebo group (0.7%). The majority of the deaths were due to trauma in both groups. These deaths did not appear related to vaccine administration.
In each treatment group, there was a death related to a deep vein thrombosis and/or pulmonary embolism, and both subjects were on hormonal contraceptives. The Gardasil recipient with this event had symptoms of leg pain prior to the first vaccination. The other Gardasil recipients who died included one subject with pancreatic cancer 578 days after dose 3, and one young male who died of arrhythmia 27 days after dose 1. This latter subject had a strong family history for arrhythmia. These events did not appear related to administration of the vaccine.
Even if all of these deaths could be explained away one way or another, this certainly sounds like a lot of deaths for such a young, and overwhelmingly female, group (16 of the 17 deaths were in females; one 15 year-old male Gardasil recipient died of a heart attack). What kind of death rate is normal for young women? The trials provide no such reference rate, but such statistics are readily available. Carnegie Mellon has a web-site called “Death Risk Rankings” (see HERE) that provides an interactive tool for calculating death rates within a wide range of demographic categories. For American females in the age range of the Gardasil trials (9-26 years of age), the rates are as follows: 2.75 per 10,000 in 10-19 year olds and 5.03 per 10,000 in 20-29 year olds. [Note: the majority of trial subjects were from the U.S. and Europe. European deaths rates from young women are 30% lower than American death rates, making this a conservative comparison].
Out of 11,778 Gardasil recipients, over 90% of them young women between the ages of 9 and 23, one would expect an annual death rate to be a mix of the rates for the two reference groups, or less than 4 per 10,000 in an entire year. But in the trials, there were three “sudden deaths”, i.e. deaths that occurred within just the two weeks of the Gardasil injections, in a review period of less than forty-five days. That’s a death rate close to ten times higher than would be expected such a short period. And the overall Gardasil death rate of 8.5 per 10,000 (10 deaths out of 11,778) for the 12 month period of the trial is more than twice what one would expect. The FDA review evinced little concern over this high death rate, preferring instead to compare the deaths in the Gardasil group to that of the “placebo” group. But as one can see from the chart below, the death rate in the aluminum adjuvant group was higher than the reference groups as well.
In short, the CBER review of Gardasil condoned the use of an immunologically active placebo and not an inert solution. So instead of a adopting an increased measure of diligence in light of the potential for bias due to the DHHS conflict of interest in Gardasil, it appears that FDA permitted Merck to use a lower standard of safety. Only by using the single set of trial data in which the placebo solution was relatively (although not entirely) inert, can one assess the impact of this relaxed standard. Based on an analysis of this data, one is drawn to an inescapable conclusion.
Gardasil was not safe.
ACIP’s recommendation for universal vaccination of young females
If the FDA was less than diligent in its review of safety profile of the anti-cancer vaccine invented at its sister agency at NIH, how did its counterparts at CDC compare in terms of their own decision processes? Faced with a choice either to take a deliberate course, allowing a period of observation to follow Gardasil’s BLA approval, or to rush Gardasil into widespread use, CDC’s approach provides another standard of comparison for DHHS’s conduct. Would their key decision-making group, the Advisory Committee on Immunization Practices (ACIP) choose the deliberate or the hasty path?
There is very little ambiguity in this answer. ACIP wasted absolutely no time in recommending Gardasil for universal use among young women. Indeed, it would have been hard for them to move any faster. In June 2006, almost immediately after FDA approval, ACIP recommended the HPV vaccination. An account in the March 23, 2007 edition of the CDC publication, Morbidity and Mortality Weekly Report (MMWR) showed that ACIP was preparing for near instantaneous approval even before the FDA’s final reviews were completed.
The Advisory Committee on Immunization Practices (ACIP) HPV vaccine workgroup first met in February 2004 to begin reviewing data related to the quadrivalent HPV vaccine. The workgroup held monthly teleconferences and meetings three times a year to review published and unpublished data from the HPV vaccine clinical trials, including data on safety, immunogenicity, and efficacy. Data on epidemiology and natural history of HPV, vaccine acceptability, and sexual behavior in the United States also were reviewed. Several economic and cost effectiveness analyses were considered. Presentations on these topics were made to ACIP during meetings in June 2005, October 2005, and February 2006. Recommendation options were developed and discussed by the ACIP HPV vaccine workgroup. When evidence was lacking, the recommendations incorporated expert opinion of the workgroup members. Options being considered by the workgroup were presented to ACIP in February 2006. The final recommendations were presented to ACIP at the June 2006 ACIP meeting. After discussions, minor modifications were made and the recommendations were approved at the June 2006 meeting.
The date of the BLA approval for Gardasil was June 6, 2006. In the June 29 ACIP meeting, just 23 days after the FDA’s decision, ACIP gave Gardasil its formal support. The vote was unanimous, with two of the fifteen members abstaining due to their financial involvements with Merck.
But not only was the vote unanimous, the mood in the meeting was celebratory. Numerous vaccine safety advocates attended the June meeting due to their concerns over the influenza vaccines. One attendee recounted the reaction to the Gardasil decision. “After the vote the place erupted in applause. There was hand-shaking and back-slapping. It seemed kind of odd and inappropriate to us.” Asked why it seemed inappropriate, the observer explained that the concern arose, “because they were so clearly cheering the recommendation. It was clear and absolutely a celebratory reaction.”
The safety discussion was almost exclusively informed, of course, by the FDA’s flawed trial data. Not surprisingly, few concerns were raised. Here’s what the ACIP minutes had to say about Gardasil’s safety profile.
The clinical trial program places strong emphasis on evaluating the safety profile of GARDASIL®. Of ~21,464 subjects, ~11,000 received detailed safety follow-up and the remainder received serious adverse experiences in medical history and pregnancy follow-up. The incidence of overall adverse events (AEs), injection-site AEs, and low-grade fevers >100°F was slightly higher in the GARDASIL® group compared to the placebo group. Systemic AEs were comparable between the two groups. Serious AEs and discontinuation due to adverse experiences were extremely rare. [emphasis added]
As a result of this accelerated process, ACIP made a series of recommendations. The first placed Gardasil on the recommended list of childhood vaccines. “ACIP recommends routine vaccination of females 11-12 years of age, with three doses of the quadrivalent HPV vaccine. The vaccine series can be started as young as nine years of age at the discretion of the provider.” In the context of the clinical trials, this was an extremely aggressive recommendation. A scant 85 pre-pubescent girls, nine years of age or younger had received Gardasil in any trial (matched with only 48 controls) and only three percent of the Gardasil trail recipients were in the range of ACIP’s target population of 11-12 year olds. Not only was ACIP basing its recommendation on flawed safety analysis, it was extending its recommendations to include groups who lay outside of even this biased assessment.
But ACIP didn’t stop there. They also recommended a catch-up vaccine for all young women, even those who would have been sexually active for many years, who had contracted at least one strain of the virus, cleared it, and therefore received diminished benefit from vaccination. “ACIP recommends vaccination for females 13-26 years of age who have not been previously vaccinated. Ideally, vaccine should be administered before onset of sexual activity, but females who are sexually active should still be vaccinated.” From a commercial perspective, this recommendation multiplied Gardasil’s profit potential for Merck and its NIH partners, creating a near term target market that was seven times larger than just the routine market of 11-12 year- olds.
There was little effective restriction placed on Gardasil’s market potential. And only the yeast protein in the carrier solution was cited as a safety concern. “Vaccination should be deferred until after moderate or severe acute illnesses improve,” read the ACIP recommendation. “A history of hypersensitivity or severe allergic reaction to yeast or any other vaccine component should be classified as a contraindication. Initiation of the vaccine series should be delayed until after completion of the pregnancy.”
The momentum for an aggressive roll-out was strong. Representatives from nine different organizations gave formal statements in support of Gardasil during the public comment period. In the meantime, and with a strong push from Merck, some state officials stood in line to move even faster than ACIP. In February of 2007, Republican Texas Gov. Rick Perry bypassed the legislature and mandated Gardasil for all 11- and 12-year-old girls in the state.
The commercial results were powerful and immediate. Merck reported its first revenues from Gardasil in the second quarter of 2006 (presumably from sales after the June BLA approval), and its revenues began to climb rapidly: $70 million in the third quarter, $155 million in the fourth quarter, all leading to a blockbuster year of 2007 in which Gardasil recorded revenues of $1.5 billion. The financial bonanza had begun in earnest.
A few years later, Merck would attract criticism for its aggressive marketing of Gardasil during this period. Sheila and David Rothman wrote a sharp critique in the Journal of the American Medical Association (hardly a radical hotbed of vaccine consumerism) in which they neglected the conflicts described here but noted the extreme measures that Merck adopted.
The marketing of this vaccine broke with traditional practices. Heretofore, vaccines had been identified by the disease they were preventing (measles, mumps) or by their creators (Salk or Sabin). This HPV vaccine followed a different model. It was identified by a trade name, Gardasil, and promoted primarily to “guard” not against HPV viruses or sexually transmitted diseases but against cervical cancer. The marketing campaign that followed, according to Merck’s chief executive officer, proceeded “flawlessly.” In 2006, Gardasil was named the pharmaceutical “brand of the year” for building “a market out of thin air.”
But the Rothmans’ critique would do little to delay or disrupt the launch. At the time of the DHHS rush to market there were few dissenting voices and none of them were heard at ACIP.
One lone voice stood out. In March 2007, just as the vaccine was reaching its peak revenue numbers, one of the doctors who had guided the clinical trials voiced an objection. On March 14, 2007, an article in a small newspaper in Fort Wayne, Indiana reported on an interview with one of the scientists involved in the clinical trials. The scientist was named Diane Harper and she expressed dismay at the ACIP recommendation.
"Giving it to 11-year-olds is a great big public health experiment," said Diane M. Harper, who is a scientist, physician, professor and the director of the Gynecologic Cancer Prevention Research Group at the Norris Cotton Cancer Center at Dartmouth Medical School in New Hampshire.
"It is silly to mandate vaccination of 11- to 12-year-old girls There also is not enough evidence gathered on side effects to know that safety is not an issue."
Harper didn’t have much to gain from the commercial success of Gardasil, but she also was taking considerable risks by breaking ranks with her colleagues. One can only imagine how things would have been different if she had been in charge of the review process at FDA rather than running one branch of the clinical trial. In the midst of such a widespread degradation in regulatory ethics and standards, it’s interesting to consider why she made that choice.
The Fort Wayne reporter, Cindy Bevington, was frank as to why Harper was telling her story to them rather than a larger media outlet. “For months, Harper said, she's been trying to convince major television and print media to listen to her and tell the facts about the usefulness and effectiveness of this vaccine.” Why was an inside critique of the Gardasil promotion campaign not already big news? "No one will print it," Harper said.
Over the coming months, the assessment of adverse effects of Gardasil would be transferred to a different group within DHHS, from CBER and ACIP to the “postlicensure safety surveillance” groups within FDA and CDC. At this point, the deaths and serious adverse events would leave the realm of closely held statistics within a vaccine manufacturer’s actively monitored trial sample and into the realm of passive surveillance in the general population; soon watchdog and vaccine safety groups like National Vaccine Information Center and Judicial Watch issued critical analyses, see HERE and HERE. And Harper’s concerns over the inadequate safety data would prove prophetic. Why had Harper broken ranks so early? When Bevington asked Harper why she was speaking out despite the momentum to the contrary, her answer was refreshingly simple.
“I want to be able to sleep with myself when I go to bed at night.”
http://www.ageofautism.com/2010/05/a-license-to-kill-part-2-who-guards-gardasils-guardians.html
A License to Kill? Part 3: After Gardasil’s Launch, More Victims, More Bad Safety Analysis and a Revolving Door Culture
May 13, 2010
A License to Kill? Part 3: After Gardasil’s Launch, More Victims, More Bad Safety Analysis and a Revolving Door Culture
By Mark Blaxill
In parts 1 (HERE) and 2 (HERE) of this series, Age of Autism identified a disturbing pattern of conflicts within the Department of Health and Human Services (DHHS) regarding Merck’s Gardasil vaccine. In an unprecedented “public-private partnership,” researchers at the National Institutes of Health (NIH) patented the technology for the “virus-like particles” (VLPs) that provoke Gardasil’s immune response to the human papillomavirus (HPV) and licensed their VLP technology to Merck. The terms of the patent license effectively made DHHS Merck’s financial partner on Gardasil, giving DHHS a clear conflict of interest on decisions regarding Gardasil.
This partnership gave Gardasil favorable treatment at key decision points, treatment that was financially rewarding to both parties. While the NIH Director celebrated his researchers’ “heroic” achievement and the researchers received numerous awards, including “Federal Employees of the Year,” officials at NIH’s sister agency, the Center for Biologic Research and Evaluation (CBER) of the Food and Drug Administration (FDA), stood watch over the Gardasil clinical trials. CBER’s review failed to hold Gardasil to a high standard of safety. Instead of comparing Gardasil to an inert placebo, as they should have, CBER based its entire safety assessment on a comparison of Gardasil’s adverse event profile with the adverse events associated with a “placebo” that was actually an immunologically active aluminum-based adjuvant. Despite the fact that an alternative comparison, pitting Gardasil against a relatively inert “carrier solution,” should have warned them of clear evidence of harm to Gardasil recipients, CBER approved Merck’s Gardasil Biologics License Application (BLA) anyway. In the meantime, following CBER’s approval of Merck’s BLA a key committee at the Centers for Disease Control and Prevention (CDC), the Advisory Committee on Immunization Practices (ACIP), put Gardasil on a fast track and immediately recommended three doses of the Gardasil vaccine to all American women between nine and twenty-six years of age. In a matter of days, Merck was guaranteed a blockbuster launch for Gardasil and within months Gardasil had reached annual revenue levels of well over $1 billion. Soon, Gardasil would become the #1 royalty generator for NIH’s technology licensing group, completing the partnership circle.
As a result of this favorable treatment at the hands of it regulatory partners at DHHS, by late 2006, Merck’s Gardasil was reaching a mass market of young American women. FDA had downplayed the fatalities associated with Gardasil in the clinical trials, but in a population of less than 12,000 young people, three sudden deaths following Gardasil and ten deaths within a year were a clear cause for concern. And as Gardasil’s reach was extending to a population numbering in the millions, the body count would soon rise. At this point in the process, the locus of DHHS conflict of interest would shift from agencies responsible for prelicensing activities such as clinical trial review and public health policy assessments to the agencies responsible for what insiders call “postlicensure surveillance” activities. The events the follow Gardasil’s launch is where part 3 of this series begins.
The body count rises
On July 20, 2008, the New York Post reported the vivid account of a mother who claimed her daughter was killed by Gardasil. In a story titled “My Girl Died As 'Guinea Pig' For Gardasil,” Lisa Ericzon’s description of her daughter’s tragic death was both detailed and disturbing. As told by the Post’s reporter, the story began like this:
“She loved SpaghettiO's, pepperoni, lilies, listening to her iPod and making her pals laugh. In her senior yearbook, she wrote, "The best things in life aren't things, they're friends." Now that's the quote chiseled into her gravestone.
Jessica Ericzon, 17, was "an all-American teenager," as described by one of her upstate LaFargeville teachers. Last February, she was working on her softball pitches, getting ready for a class trip to Universal Studios in Florida and hitting the slopes to snowboard with her older brother. Then one day, the blond, blue-eyed honors student collapsed dead in her bathroom. It started with a pain in the back of her head.
On the advice of her family doctor, Jessie had taken a series of three Gardasil shots.
Sadly, Jessica Ericzon’s death was not an isolated incident. Since Gardasil’s launch in late 2006, a rising number of parents have stepped forward to report the deaths of their daughters at the hands of the vaccine. Gardasil has now become a global product, so these reports have come from around the world; but the United States is by far Merck’s largest market, so most of the reported fatalities have come from closer to home. Jessica Ericzon came from upstate New York, about a mile south of the Canadian border, and her parents were among the first to go public about Gardasil. But they haven’t been the last. There are at least ten public reports of young women allegedly killed by Gardasil in the months since FDA approved Merck’s BLA on June 8, 2006. Many more have been reported privately to the CDC.
In contrast to Jessica’s sudden death, and just a few weeks before the New York Post headline and article, another family went public with their daughter’s plight, in a blog named “Jenny’s Journey.” In their introductory blog post, Jennifer Tetlock’s parents relayed an urgent request. Their daughter wasn’t dead, but she was dying from what Jenny’s doctors had theorized was a rare degenerative neurological condition, an unusual form of early onset amyotrophic lateral sclerosis (or ALS, popularly known as Lou Gehrig’s disease). The bloggers, Barbara Mellers, Philip Tetlock, and Barbara Shapiro, were in no sense activists, and weren’t eager to join what they later termed the “anti-Gardasil movement.” What they wanted most of all was to find a way to save their daughter’s life. “One of the major things that would help her doctors figure out what to do”, they wrote on June 6, 2008, “is to find other people like Jenny (called "comparables")--people that share her medical condition and perhaps have had luck with certain treatments.”
The list of Gardasil victims who have gone public--parents of young women like Jessica Ericzon and Jennifer Tetlock--provides only a fragmentary view of the death toll associated with Gardasil. Many more deaths have been reported to the Vaccine Adverse Events Reporting System (VAERS) in cases where the family has chosen not to go public with their tragic loss. Among the short list of publicized cases, most simply dropped dead like Jessica Ericzon within days of receiving a dose of the vaccine; these cases most closely resembled the three cases of sudden death from Gardasil reported during the clinical trials. Cases of clear “comparables” to Jenny Tetlock, young women who could satisfy Jenny’s parents’ quest, were less common. Nevertheless, there were a number of these publicly reported cases in which a Gardasil shot seemed to trigger a downward spiral of ill health-- encompassing a diverse range of symptoms--that would culminate in death (many of which came on suddenly as well).
The table below summarizes the connection between Gardasil and ten deaths that have been publicly associated with the vaccine. All of these stories have been reported elsewhere, most of them assembled in a memorial web-site called “The Truth About Gardasil.” You can find go to this web-site to read more about the stories of many of these young women (see HERE).
Name
Date of First Vaccine
Date of Death
Reported Cause, Complications and Timing of Death
1
Santana Valdez
Dec, 2006?
Aug 31, 2007
Sudden death, with airway papillomatosis, less than 4 months after 3rd dose
2
Jenny Tetlock
Mar, 2007
Mar 15, 2009
Juvenile amyotrophic lateral sclerosis with onset after 1st dose
3
Brooke Petkevicius
Mar, 2007
Mar 26, 2007
Sudden death, with seizure and pulmonary embolism, 2 weeks after 1st dose
4
Jessica Ericzon
Jul, 2007
Feb 12, 2008
Sudden death, 1 day after 3rd dose after neurological symptoms
5
Jasmin Soriat
Sep, 2007
Oct 12,
2007
Sudden death, with “respiratory paralysis,” less than 1 month after 1st dose
6
Amber Kaufman
Mar, 2008
Apr 7,
2008
Sudden death, with seizure, “cardiac disturbance of undetermined etiology,” 1 week after 2nd dose
7
Christina Tarsell
Jun, 2008
Jun 23,
2008
Sudden death, 2 weeks after 3rd dose after symptoms of dizziness and fatigue
8
Moshella Roberts
Apr, 2008
Apr 5,
2008
Sudden death, 4 days after 1st dose
9
Megan Hild
May/Jun, 2008?
Nov 15, 2008
Sudden death, 2 months after 2nd dose after “severe headaches” and “severe stomach pain”
10
Jasmine Renata
Sept, 2008
Sept 21, 2009
Sudden death 6 months after 3rd dose after increasing cardiac and neurological symptoms
These public reports provide varying degrees of detail regarding cause of death. In one case (one where substantial detail has been reported), a young woman named Brooke Petkevicius who died suddenly after her first dose of Gardasil showed symptoms remarkably similar to a case report detailed in CBER’s clinical trial review. The February 6, 2008 edition of East Bay Express (see HERE), a San Francisco Bay Area newspaper, provided the following account.
In early 2007, as the pharmaceutical giant Merck began promoting its new vaccine Gardasil as protection against cervical cancer, Brooke Petkevicius was a nineteen-year-old freshman at UC Berkeley. She had seen the ads for the vaccine, and discussed getting it with her mother, whose gynecologist also had recommended it. On March 12, Brooke received the first of three doses. Two weeks later, she dressed to go running with a friend. As they reached the elevator, Brooke suddenly collapsed against the wall and had a seizure.
"She started shaking a lot," recalled the friend, Kristin Bietsch. "And her eyes went glazy a little bit." An ambulance rushed Petkevicius to the hospital, but doctors couldn't save her. Her autopsy indicated that she was killed by a pulmonary embolism, or blood clot, which had blocked the artery between her heart and lungs. "She had a whole bunch of little floating clots in her system," said her mother, Debra Sonner, recalling what doctors told her at the time.
Was Brooke’s death just a random coincidence or were there clues from the early safety reviews that anticipated her tragic death? One needn’t look far for comparable stories: the following account comes from one of the three sudden deaths after Gardasil reported in the clinical trials.
This 22 year old non-smoking white female subject had symptoms of leg pain prior to the vaccination (11/15/02), and was seeing a masseur for this complaint. She was also on hormonal contraceptives. The subject was vaccinated with her first dose of Gardasil on -------. On --------, Day 19 Postdose 1, the subject experienced suspected deep vein thrombophlebitis (DVT) of the left leg and consulted her own general practitioner. On --------, Day 20 Postdose 1, the subject experienced severe chest pain and was taken to the emergency room (ER). The subject subsequently experienced a suspected acute massive pulmonary embolism of severe intensity and was admitted to the intensive care unit (ICU). Echocardiography was performed and showed normal aorta and no thrombosis in the vena cava. Abdominal ultrasound was performed with no abnormal findings. On the same day, the subject died of acute massive pulmonary embolism and deep vein thrombosis of the left leg. The autopsy report confirmed the diagnosis of acute massive pulmonary embolism and deep thrombophlebitis of the left leg and also revealed an incidental finding of acute ischemic renal failure.
As this account suggests, the CBER review eventually explained away this death as a coincidence, an unfortunate side effect of taking birth control pills in a situation where the victim suffered from a pre-existing condition. So as soon as reports of similar deaths began entering the VAERS system, the CDC found ways to dismiss comparable cases such as Brooke Petkevicius by pointing a finger at birth-control pills as well. In a June 2007 report on the early deaths from Gardasil that were reported to the Vaccine Adverse Event Reporting System (VAERS), CDC dismissed Brooke’s death as yet another coincidence. “Preliminary data indicate that the two women [including Brooke], who died of blood clots were taking birth-control pills, and blood clots are a known risk associated with birth-control pills. All four deaths are being fully investigated but none appear to be caused by vaccination," claimed CDC. With regard to Gardasil, CDC wrote in its defense, "Since more than 5 million doses have been distributed, some deaths will occur coincidentally following vaccination (but not due to vaccination)."
Blaming the victim and citing coincidental death following vaccination are two well-known tactics that long ago became part of the DHHS playbook and CDC is not alone in deploying this tactic. In addition to the pulmonary embolism described above, the CBER review dismissed the two other cases of sudden death following Gardasil. One such case was a 15-year old boy who died of a heart attack less than a month after his first dose of Gardasil; yet CBER reported “the autopsy was inconclusive, but there was a strong family history of arrhythmia.” The other case was a 21 year-old woman who died with a convulsion four days after her third Gardasil dose; the CBER review again blamed this victim for her death, reporting that “this subject had a history of seizure disorder and anxiety. She suffered a seizure 4 days after dose 3, and was noted to have cocaine in her urine.”
Natural skepticism aside, making sense of individual cases like the ten public death reports and the three sudden deaths in the Gardasil trials is tricky business. Without intensive medical investigations one may never find definitive proof of harm from Gardasil. And, of course, the vast majority of Gardasil recipients have survived their vaccination series with no discernible lasting effects. There can be little dispute, however, that Merck has an enormous incentive to downplay obstacles to a profitable new product like Gardasil. And unfortunately, as we’ve seen in the clinical trial cases, FDA appears to have shared Merck’s bias, acting more like an equity participant in a DHHS “public-private partnership” than a conscientious guardian of the public trust; Its CBER reviewers effectively turned a blind eye to troubling signals as they granted Merck its BLA for Gardasil. Inevitably, however, a persuasive critique of vaccine safety monitoring for a blockbuster vaccine like Gardasil needs to move away from the realm of anecdote and into the realm of statistics. As we move beyond the review of individual cases, we’ll take a closer look at whether or not DHHS officials displayed notable biases in their analyses of Gardasil’s adverse effects in larger populations and how those analyses have been criticized by others.
Lack of diligence in postlicensure safety surveillance
Responsibility for what public health officials call “postlicensure safety surveillance” falls to a small set of DHHS departments. Two of these are the FDA’s Vaccine Safety Branch (VSB) and the CDC’s Immunization Safety Office (ISO). After CBER approves a vaccine and ACIP recommends it, the baton within DHHS passes next to VSB and ISO. In the passing of this baton, as stipulated previously, the presence of a conflict of interest does not mean that regulatory activity will necessarily reflect bias, negligence or lack of diligence on the part of the next group of regulators: Each department’s work deserves to be judged on its own merits. But in light of what appears to be a clear pattern of bias in the prelicensure activities of DHHS, it’s reasonable to approach an assessment of postlicensure activities with some skepticism. What, then, does the public record of postlicensure surveillance activity say about the presence of absence of bias and how VSB and ISO have done their jobs in assessing Gardasil’s safety?
The main public output of the FDA and CDC groups’ work has so far come in a single report published in the August 19, 2009 issue of the Journal of the American Medical Association (JAMA). In that paper, ISO’s Barbara Slade and four of her colleagues from CDC joined together with seven FDA colleagues to publish the first-ever analysis of the VAERS data on Gardasil. Not surprisingly, the JAMA paper gave Gardasil a free pass; in the process the authors joined the chorus of DHHS celebration for the breakthrough of its home-grown anti-cancer vaccine. “Vaccination with [Gardasil] has the potential to decrease the global morbidity and mortality of HPV-associated diseases, including cervical cancer. After hepatitis B vaccine, which can prevent liver cancer, [Gardasil] is only the second vaccine licensed with an indication to prevent cancer.” And although they acknowledged the possibility of injury due to blood clots like those that killed Brooke Petkevicius, Slade et al argued that the data from VAERS led to the same conclusion as the positive review from their colleagues at CBER. “The postlicensure safety profile presented here is broadly consistent with safety data from prelicensure trials.”
As for the specific question of Gardasil deaths, Slade et al acknowledged that there had been deaths associated with Gardasil. But they dismissed the VAERS death reports as not frequent enough to worry about.
Causes of death included 4 unexplained deaths, 2 cases of diabetic ketoacidosis (1 complicated by pulmonary embolism), 1 case related to prescription drug abuse, 1 case of juvenile amyotropic lateral sclerosis, 1 case of meningoencephalitis (Neisseria meningitidis serogroup B), 1 case of influenza B viral sepsis, 3 cases of pulmonary embolism (1 associated with hyperviscosity due to diabetic ketoacidosis), 6 cardiac-related deaths (4 arrhythmias and 2 cases of myocarditis), and 2 cases due to idiopathic seizure disorder. The PRR [statistics speak for “proportional reporting ratio”, or the VAERS death rate relative to the “background” expected death rate] for deaths in 6- to 17-yearolds was 1.4 (Χ2=0.42, P=.52). The PRR for deaths in 8- to 29-year-olds was 1.2 (Χ2=0.01, P=.92). Neither of these met the screening criteria for signal detection. [emphasis added]
Criticism of the JAMA analysis came quickly (some preceded the paper’s publication) and from several different quarters. One of the most trenchant attacked the relevance of the VAERS case data itself and came from the parents of a Gardasil victim. Like so many parents of vaccine injured children, Jennifer Tetlock’s parents had become deeply dissatisfied by the diligence of federal officials in evaluating Gardasil’s safety. Jennifer’s adverse reaction, as originally diagnosed, was among the least common adverse events; Slade et al reported it as an isolated case. But in April 2009, Jenny’s parents publicly voiced their suspicion that their doctor’s original diagnosis of juvenile amyotrophic lateral sclerosis may have been misleadingly narrow. They argued that “world-class immunologists suspect that Jenny had a potentially treatable autoimmune disorder mimicking ALS, possibly triggered by the Gardasil vaccination.” If true, this interpretation of her reaction placed Jenny’s death in a broader category of a severe autoimmune reactions from Gardasil. As reported previously in part 2, this kind of autoimmune reaction was a risk that the clinical trials showed to be quite common.
More broadly, Jenny’s parents struck out at CDC’s failure of postlicensure diligence.
The CDC does not inspire confidence, so we conducted our own shoestring search to determine whether Jenny was alone. We created a website (jenjensfamilyblogspot.com). Although this website has only drawn 40,000 visitors, it has out-performed the federal government in finding girls ominously similar to Jenny (current score is: Jenny site 2; CDC’s VAERS: 0).
One does not need to be a statistician to see how unlikely it is that these two other girls are the only cases out there—or how frightening it is that we already know of three documented cases of girls (those two plus Jenny) who developed ALS within several months after their vaccinations. After all, if the odds of ALS in teenaged girls are 1 in 3 million and we found 3 in only 40,000, it is very possible that many other of the 6 million girls vaccinated have already developed severe neurological collapse, like Jenny.
Jenny’s parents may have been uncertain about the proper diagnosis of Jenny’s reaction, but they were not alone in their criticism of the statistics underlying the FDA/CDC analysis. In a December 2009 letter to JAMA, Drs. Vicky Debold (Full disclosure: Debold is a director of the Age of Autism sponsor SafeMinds) and Eric Hurwitz criticized the Slade analysis. Debold and Hurwitz identified numerous flaws in the CDC/FDA report, arguing that: a) cases of autoimmune diseases such as Guillain-Barré syndrome were systematically underreported; b) the method for obtaining background rates of disease could include vaccine injury and were thus inappropriate to use in comparisons; and c) the denominator for the case population used to generate the PRRs was grossly overstated. On the last point, Debold and Hurwitz noted that Slade et al had mistakenly used “total vaccine doses distributed” as the denominator for disease rates instead of doses administered (or for that matter the number of women receiving doses), a choice that “systematically inflates the ratio’s denominator.”
Debold and Hurwitz noted the larger policy problem created by these failures in postlicensure surveillance and by Slade et al’s low standard of diligence. “Federal officials have cited this study as evidence that [Gardasil] ‘is a safe and effective vaccine,’” they noted. “However, we consider that conclusion to be unwarranted because the study draws inferences from data likely to be systematically biased.”
Diane Harper, one of the researchers involved in the Gardasil trials, agreed with Debold and Hurwitz. In an August 2009 interview with CBS News reporter Sharyl Attkisson, she also criticized Slade et al, arguing to Attkisson that “the risks of vaccination are underreported in Slade's article, as they are based on a denominator of doses distributed from Merck's warehouse. Up to a third of those doses may be in refrigerators waiting to be dispensed as the autumn onslaught of vaccine messages is sent home to parents the first day of school. Should the denominator in Dr. Slade's work be adjusted to account for this, and then divided by three for the number of women who would receive all three doses, the incidence rate of serious adverse events increases up to five fold" [emphasis added].
Harper also agreed with Jenny Tetlock’s parents’ suggestion that Slade et al were understating the number of deaths in their risk assessment, the numerator. Harper told Attkisson, "Parents and women must know that deaths occurred. Not all deaths that have been reported were represented in Dr. Slade's work, one-third of the death reports were unavailable to the CDC, leaving the parents of the deceased teenagers in despair that the CDC is ignoring the very rare but real occurrences that need not have happened if parents were given information stating that there are real, but small risks of death surrounding the administration of Gardasil."
So how should one weigh the net impact of all these claims and criticisms? Certainly, although there are serious health risks, including death, associated with Gardasil, there are also potential benefits, including reduced rates of cervical cancer. Slade’s analysis doesn’t provide the number of individuals receiving vaccine in the first two years after the Merck vaccine’s introduction, but based on the statistics she provides, it’s reasonable to assume that something less than 10 million young women received doses of Gardasil (23 million doses distributed with a target of 3 doses per subject). A balanced review of the overall benefits of Gardasil would compare the frequency and consequences of vaccine injury in this population, based on the most objective rate of adverse events, with the vaccine’s purported benefits.
If we compare the death rate (these rates were calculated in part 2 of this series) in the Gardasil trial group of 8.5 per 10,000 to an expected death rate in young women of 3.9 per 10,000, we get an extra death risk from Gardasil of roughly 4-5 per 10,000 annually. Applied to a population of 4 million young women per year, that would come to a total of close to 2,000 extra deaths per year that were caused by Gardasil during the period of its launch. This is an extraordinarily high rate and may possibly be explained away by bad luck and coincidences, as the CBER review contended. But it is the only active surveillance analysis ever done on a population exposed to Gardasil. By contrast, the calculated death rate from VAERS reports gives a much lower number, over 100 times lower, a ratio that many consumer advocates (and certainly Jennifer Tetlock’s parents) believe reflects more on the poor quality of the VAERS database than the actual risk of death from Gardasil.
But if Gardasil is successful in preventing deaths from cervical cancer, is it possible that society is still coming out ahead overall? The America Cancer Society estimates that there were 4,000 deaths in 2009 from cervical cancer. If Gardasil could prevent a significant number of these deaths in the future, then it’s possible that the benefits of the vaccine might exceed the risks. Unfortunately for the vaccine program, the deaths caused by Gardasil are immediate and the preventable deaths from cervical cancer are many years away.
Unfortunately for the public, in assessing the reliability of any estimates of Gardasil’s future benefits there are many unknowns: we don’t know how long the immunity against HPV will last; we don’t know whether costly booster shots and a new round of adverse events will be necessary; and, most important of all, we don’t yet have any idea whether or not Gardasil will succeed in preventing a meaningful number of cervical cancer deaths. We know it provides effective immunity against two of the most common cancer-causing strains of HPV. But it’s entirely possible that, just as soon Gardasil suppresses these strains of HPV, new cancerous strains will arise to take their place leaving overall cervical cancer rates unchanged. The dirty little secret of the war on cervical cancer is that public health officials have no current way to judge how and whether widespread vaccination with Gardasil will affect the actual rate of cervical cancer and they won’t be able to make that judgment for many years.
A similar situation holds in the case of a similarly multi-strain infection and its associated vaccine formulation: in this case the many different strains of streptococcus pneumoniae, the bacterial species responsible for invasive pneumoccoal disease (or IPD) and the so-called pneumococcal vaccine. In order to combat IPD, a leading cause of bacterial meningitis, a multi-strain vaccine called Prevnar was introduced by Wyeth in 2000. Prevnar quickly became one of the most commercially successful vaccines of all time, bringing in nearly $3 billion in revenue in 2008. But in asking whether Gardasil will actually work against cervical cancer, it’s useful to ask whether a similar vaccine product like Prevnar has been successful in actually preventing IPD?
A recent study from Massachusetts on its effectiveness suggests that Prevnar, contrary to all expectations, did not reduce the incidence of IPD in the state. Instead, although the forms of IPD caused by strains in the vaccine went down after Prevnar’s introduction, IPD cases caused by other strains (some of which were even more dangerous than the original strains) rose almost immediately and in opposite proportions, to keep the rate of IPD in Massachusetts constant. In plain language, Prevnar, the most commercially valuable vaccine in history, created no health benefits whatsoever. It just didn’t work.
Will this be the case with Gardasil? We will only know with any certainty what Gardasil’s benefits will be after many years, even decades of use. Right now, it’s too early to tell how many of the 4,000 annual deaths from cervical cancer might be prevented. But several things are clear in the near term: Gardasil has already injured an unknown number of young women, with these injuries likely including deaths that may number in the hundreds, possibly (based on the only data available) as many as 2,000 per year; Gardasil also has left many more young women with crippling chronic conditions like Guillain-Barré syndrome, arthritis and autoimmune thyroid conditions.
Diane Harper has also argued that assessments of the net benefits of Gardasil have overstated its value. She told Sharyl Attkisson in her interview that, "the risks of serious adverse events including death reported after Gardasil use in the JAMA article by CDC’s Dr. Barbara Slade were 3.4/100,000 doses distributed.” This rate is substantially lower than our estimates here. Nevertheless, Harper remained concerned that Gardasil’s risks outweighed its benefits. “The rate of serious adverse events is on par with the death rate of cervical cancer. Gardasil has been associated with at least as many serious adverse events as there are deaths from cervical cancer developing each year.”
In light of the many years required to prevent cases of cervical cancer, it’s clear that the current cost of Gardasil outweighs its current benefit. Moreover, it may take many years to realize any net benefit to society from Gardasil; the crossover point where realized benefits exceed the costs incurred is far away and uncertain. At the moment, therefore, there is only one net benefit that is certain: the benefit to Merck’s bottom line. And, of course, the bottom line of Merck’s business partner at NIH.
Revolving door culture
DHHS has a clear conflict of interest with respect to Gardasil at the institutional level since it shares directly in Gardasil’s profits. We’ve also seen now that this conflict of interest is echoed by (and possibly sustains) a pervasive pattern of regulatory bias in favor of Gardasil during multiple stages of the decision process. But as the Gardasil body count rises, one natural question one might ask is why, at a personal level, more DHHS officials haven’t taken the principled stand of Diane Harper, who spoke up against the ACIP Gardasil recommendation because “I want to be able to sleep with myself when I go to bed at night.”
In the case of several senior officials involved in overseeing key DHHS decisions during the Gardasil era, some portion of that answer is provided by their subsequent career moves. Indeed, these moves reveal a cultural problem that is in many ways more troubling than the direct Gardasil financial conflicts: a pervasive pattern of senior officials cashing in on their careers in public service in order to obtain lucrative corporate and consulting jobs. The career moves of these senior officials show that a virtual revolving door between regulators and the pharmaceutical, vaccine and biologics companies they are supposed to regulate erodes any meaningful sense in which these officials truly serve consumer interests, especially when it comes to product safety. This revolving door provides the cultural foundation that undergirds some of the more egregious institutional conflicts.
A short account of the recent careers of just a few of the officials involved in regulating Gardasil shows this revolving door in action.
• Mike Leavitt was named on December 13, 2004 as Secretary of DHHS, where he subsequently was responsible most of the critical regulatory decisions involving Gardasil. In January 2009, he left HHS and formed Leavitt Partners, a Washington DC consulting firm that helps its client “enter new markets, enhance the value of their products and navigate dynamic regulatory and reimbursement systems.” In his consulting work, Leavitt could certainly teach his clients about Gardasil and how they could follow Merck’s example in forging a model “public-private partnership.”
• Julie Gerberding was named Director of CDC on July 3, 2002 and served in that role until she resigned on January 29, 2009. Gerberding watched over Gardasil policy at CDC during the period of FDA review in which ACIP put Gardasil on a fast track for approval in June 2006. She also was in charge of the oversight for CDC’s postlicensure safety activities during much of the period leading up to Slade et al’s JAMA submission when portions of the VAERS analysis were reviewed with ACIP. Less than a year after leaving public service, on December 21, 2009, Merck announced Gerberding’s appointment as President of the Merck Vaccine Division, effective January 25, 2010, the minimum interval allowed for a Federal official to assume a position at a company they used to regulate. Gerberding, who once regulated Gardasil, is now directly responsible for its growth and profitability.
• Karen Goldenthal was the Director of the Division of Vaccines and Related Products Applications within CBER, the FDA division responsible for approving Gardasil’s BLA in June 2006. In 2007, shortly after Gardasil’s approval, Goldenthal left CBER to become Executive Director of PharmaNet Consulting. PharmaNet is “a global, drug development services company, provides a comprehensive range of services to the pharmaceutical, biotechnology, generic drug, and medical device industries.” Other FDA executives have taken leadership positions at PharmaNet, including William Egan, former head of Vaccine Research and Review at FDA, now a Vice President in PharmaNet’s consulting practice.
These departures provide just a few small examples of a pervasive exodus of FDA officials, many of whom leave FDA in order to provide advice to pharmaceutical companies on how to make their way successfully through the pre- and post-licensure processes. And when it comes to vaccines, there is a specific market for former CBER officials to coach vaccine manufacturers on how to get their BLAs approved and their launches more profitable. Like PharmaNet, a consulting company called the Biologics Consulting Group (BCG) shows how active the revolving door between FDA and industry has become. Here’s how BCG describes itself.
Biologics Consulting Group, Inc. (BCG) is a team of consultants who provide national and international regulatory and product development advice on the development and commercial production of biological, drug and device products. Our staff consists of experts in regulatory affairs, product manufacturing and testing, pharmacology/toxicology, facility inspections, statistics, program management, and clinical trial design and evaluation. Many of our consultants are former CBER, CDER, and CDRH reviewers. [emphasis added]
In an environment so stepped in both direct and indirect conflicts of interest, is it any wonder that Gardasil regulators have leaned so steeply in favor of industry while overlooking serious safety concerns?
The early victims of Gardasil look for justice
The final phase of regulatory activities surrounding Gardasil have yet to play themselves out. These involve the process of adjudicating claims of injury and death due to the vaccine. The DHHS agency responsible for this work is the Health Resources Services Agency (HRSA), which houses the Division of Vaccine Injury Compensation, the group responsible for managing the Vaccine Injury Compensation Program (VICP), more commonly known as “vaccine court.” In light of the pattern of bias we’ve observed in the approach other DHHS agencies have taken to Gardasil, one might reasonably question the prospects for fair treatment of Gardasil victims in vaccine court. Can we really expect the director of HRSA to encourage a fair and generous compensation policy on Gardasil when her colleagues over at NIH are profiting from the patent license, CDC is actively promoting its use and her former colleagues at FDA are providing consulting services to companies helping them avoid regulatory pitfalls and keep their profits intact?
As in the case of its sister agencies, the presence of conflict of interest does not necessarily mean that HRSA will demonstrate bias, negligence or failures of diligence in their approach to Gardasil. In advance of any record of decisions, however, it’s simply too early to tell how HRSA will respond. In other controversial areas such as the Autism Omnibus Proceeding, petitioners have been deeply disappointed in their treatment at the hands of the vaccine court. And it seems likely that Gardasil families are destined for their own day in vaccine court: HRSA provides “table injuries” that provide compensation for a short list of outcomes on a few vaccines, but there are no table injuries yet specified for Gardasil. (HRSA has commissioned the Institute of Medicine to develop such a list for the entire category of HPV vaccines. A candidate list of injuries can be found in the latest working list from the “Committee to Review Adverse Events of Vaccines”, see HERE ) So as Gardasil petitioners find their way into the VICP process, HRSA officials will be setting Gardasil injury compensation policy for the first time.
And the Gardasil girls are coming to seek justice. In an early action, on March 13, 2010, the parents of Jennifer Tetlock filed the following petition with the VICP.
The above captioned Petitioners request compensation under the National Vaccine Injury Compensation Program, 42 U.S.C. 300aa-10 et seq. (Supp. 1996), for the death of minor, Jennifer Tetlock who received the third series of the Gardasil vaccination on March 1, 2007 from James Cuthbertson, M.D. in Berkeley, California and thereafter suffered from atypical amyotrophic lateral sclerosis (ALS)-like lower motor neuron disease which was caused in fact by the above stated vaccination.
Will Jennifer Tetlock receive justice? It’s hard to imagine how any agency so inextricably linked to the Gardasil program--from invention to approval and recommendation to protection and profit—can possibly be trusted to be a fair arbiter of guilt and innocence.
But one can always hope. After all, the guardians of vaccine safety in DHHS have children themselves. And like Diane Harper, they also need to sleep with themselves when they go to bed at night.
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A License to Kill? Part 3: After Gardasil’s Launch, More Victims, More Bad Safety Analysis and a Revolving Door Culture
By Mark Blaxill
In parts 1 (HERE) and 2 (HERE) of this series, Age of Autism identified a disturbing pattern of conflicts within the Department of Health and Human Services (DHHS) regarding Merck’s Gardasil vaccine. In an unprecedented “public-private partnership,” researchers at the National Institutes of Health (NIH) patented the technology for the “virus-like particles” (VLPs) that provoke Gardasil’s immune response to the human papillomavirus (HPV) and licensed their VLP technology to Merck. The terms of the patent license effectively made DHHS Merck’s financial partner on Gardasil, giving DHHS a clear conflict of interest on decisions regarding Gardasil.
This partnership gave Gardasil favorable treatment at key decision points, treatment that was financially rewarding to both parties. While the NIH Director celebrated his researchers’ “heroic” achievement and the researchers received numerous awards, including “Federal Employees of the Year,” officials at NIH’s sister agency, the Center for Biologic Research and Evaluation (CBER) of the Food and Drug Administration (FDA), stood watch over the Gardasil clinical trials. CBER’s review failed to hold Gardasil to a high standard of safety. Instead of comparing Gardasil to an inert placebo, as they should have, CBER based its entire safety assessment on a comparison of Gardasil’s adverse event profile with the adverse events associated with a “placebo” that was actually an immunologically active aluminum-based adjuvant. Despite the fact that an alternative comparison, pitting Gardasil against a relatively inert “carrier solution,” should have warned them of clear evidence of harm to Gardasil recipients, CBER approved Merck’s Gardasil Biologics License Application (BLA) anyway. In the meantime, following CBER’s approval of Merck’s BLA a key committee at the Centers for Disease Control and Prevention (CDC), the Advisory Committee on Immunization Practices (ACIP), put Gardasil on a fast track and immediately recommended three doses of the Gardasil vaccine to all American women between nine and twenty-six years of age. In a matter of days, Merck was guaranteed a blockbuster launch for Gardasil and within months Gardasil had reached annual revenue levels of well over $1 billion. Soon, Gardasil would become the #1 royalty generator for NIH’s technology licensing group, completing the partnership circle.
As a result of this favorable treatment at the hands of it regulatory partners at DHHS, by late 2006, Merck’s Gardasil was reaching a mass market of young American women. FDA had downplayed the fatalities associated with Gardasil in the clinical trials, but in a population of less than 12,000 young people, three sudden deaths following Gardasil and ten deaths within a year were a clear cause for concern. And as Gardasil’s reach was extending to a population numbering in the millions, the body count would soon rise. At this point in the process, the locus of DHHS conflict of interest would shift from agencies responsible for prelicensing activities such as clinical trial review and public health policy assessments to the agencies responsible for what insiders call “postlicensure surveillance” activities. The events the follow Gardasil’s launch is where part 3 of this series begins.
The body count rises
On July 20, 2008, the New York Post reported the vivid account of a mother who claimed her daughter was killed by Gardasil. In a story titled “My Girl Died As 'Guinea Pig' For Gardasil,” Lisa Ericzon’s description of her daughter’s tragic death was both detailed and disturbing. As told by the Post’s reporter, the story began like this:
“She loved SpaghettiO's, pepperoni, lilies, listening to her iPod and making her pals laugh. In her senior yearbook, she wrote, "The best things in life aren't things, they're friends." Now that's the quote chiseled into her gravestone.
Jessica Ericzon, 17, was "an all-American teenager," as described by one of her upstate LaFargeville teachers. Last February, she was working on her softball pitches, getting ready for a class trip to Universal Studios in Florida and hitting the slopes to snowboard with her older brother. Then one day, the blond, blue-eyed honors student collapsed dead in her bathroom. It started with a pain in the back of her head.
On the advice of her family doctor, Jessie had taken a series of three Gardasil shots.
Sadly, Jessica Ericzon’s death was not an isolated incident. Since Gardasil’s launch in late 2006, a rising number of parents have stepped forward to report the deaths of their daughters at the hands of the vaccine. Gardasil has now become a global product, so these reports have come from around the world; but the United States is by far Merck’s largest market, so most of the reported fatalities have come from closer to home. Jessica Ericzon came from upstate New York, about a mile south of the Canadian border, and her parents were among the first to go public about Gardasil. But they haven’t been the last. There are at least ten public reports of young women allegedly killed by Gardasil in the months since FDA approved Merck’s BLA on June 8, 2006. Many more have been reported privately to the CDC.
In contrast to Jessica’s sudden death, and just a few weeks before the New York Post headline and article, another family went public with their daughter’s plight, in a blog named “Jenny’s Journey.” In their introductory blog post, Jennifer Tetlock’s parents relayed an urgent request. Their daughter wasn’t dead, but she was dying from what Jenny’s doctors had theorized was a rare degenerative neurological condition, an unusual form of early onset amyotrophic lateral sclerosis (or ALS, popularly known as Lou Gehrig’s disease). The bloggers, Barbara Mellers, Philip Tetlock, and Barbara Shapiro, were in no sense activists, and weren’t eager to join what they later termed the “anti-Gardasil movement.” What they wanted most of all was to find a way to save their daughter’s life. “One of the major things that would help her doctors figure out what to do”, they wrote on June 6, 2008, “is to find other people like Jenny (called "comparables")--people that share her medical condition and perhaps have had luck with certain treatments.”
The list of Gardasil victims who have gone public--parents of young women like Jessica Ericzon and Jennifer Tetlock--provides only a fragmentary view of the death toll associated with Gardasil. Many more deaths have been reported to the Vaccine Adverse Events Reporting System (VAERS) in cases where the family has chosen not to go public with their tragic loss. Among the short list of publicized cases, most simply dropped dead like Jessica Ericzon within days of receiving a dose of the vaccine; these cases most closely resembled the three cases of sudden death from Gardasil reported during the clinical trials. Cases of clear “comparables” to Jenny Tetlock, young women who could satisfy Jenny’s parents’ quest, were less common. Nevertheless, there were a number of these publicly reported cases in which a Gardasil shot seemed to trigger a downward spiral of ill health-- encompassing a diverse range of symptoms--that would culminate in death (many of which came on suddenly as well).
The table below summarizes the connection between Gardasil and ten deaths that have been publicly associated with the vaccine. All of these stories have been reported elsewhere, most of them assembled in a memorial web-site called “The Truth About Gardasil.” You can find go to this web-site to read more about the stories of many of these young women (see HERE).
Name
Date of First Vaccine
Date of Death
Reported Cause, Complications and Timing of Death
1
Santana Valdez
Dec, 2006?
Aug 31, 2007
Sudden death, with airway papillomatosis, less than 4 months after 3rd dose
2
Jenny Tetlock
Mar, 2007
Mar 15, 2009
Juvenile amyotrophic lateral sclerosis with onset after 1st dose
3
Brooke Petkevicius
Mar, 2007
Mar 26, 2007
Sudden death, with seizure and pulmonary embolism, 2 weeks after 1st dose
4
Jessica Ericzon
Jul, 2007
Feb 12, 2008
Sudden death, 1 day after 3rd dose after neurological symptoms
5
Jasmin Soriat
Sep, 2007
Oct 12,
2007
Sudden death, with “respiratory paralysis,” less than 1 month after 1st dose
6
Amber Kaufman
Mar, 2008
Apr 7,
2008
Sudden death, with seizure, “cardiac disturbance of undetermined etiology,” 1 week after 2nd dose
7
Christina Tarsell
Jun, 2008
Jun 23,
2008
Sudden death, 2 weeks after 3rd dose after symptoms of dizziness and fatigue
8
Moshella Roberts
Apr, 2008
Apr 5,
2008
Sudden death, 4 days after 1st dose
9
Megan Hild
May/Jun, 2008?
Nov 15, 2008
Sudden death, 2 months after 2nd dose after “severe headaches” and “severe stomach pain”
10
Jasmine Renata
Sept, 2008
Sept 21, 2009
Sudden death 6 months after 3rd dose after increasing cardiac and neurological symptoms
These public reports provide varying degrees of detail regarding cause of death. In one case (one where substantial detail has been reported), a young woman named Brooke Petkevicius who died suddenly after her first dose of Gardasil showed symptoms remarkably similar to a case report detailed in CBER’s clinical trial review. The February 6, 2008 edition of East Bay Express (see HERE), a San Francisco Bay Area newspaper, provided the following account.
In early 2007, as the pharmaceutical giant Merck began promoting its new vaccine Gardasil as protection against cervical cancer, Brooke Petkevicius was a nineteen-year-old freshman at UC Berkeley. She had seen the ads for the vaccine, and discussed getting it with her mother, whose gynecologist also had recommended it. On March 12, Brooke received the first of three doses. Two weeks later, she dressed to go running with a friend. As they reached the elevator, Brooke suddenly collapsed against the wall and had a seizure.
"She started shaking a lot," recalled the friend, Kristin Bietsch. "And her eyes went glazy a little bit." An ambulance rushed Petkevicius to the hospital, but doctors couldn't save her. Her autopsy indicated that she was killed by a pulmonary embolism, or blood clot, which had blocked the artery between her heart and lungs. "She had a whole bunch of little floating clots in her system," said her mother, Debra Sonner, recalling what doctors told her at the time.
Was Brooke’s death just a random coincidence or were there clues from the early safety reviews that anticipated her tragic death? One needn’t look far for comparable stories: the following account comes from one of the three sudden deaths after Gardasil reported in the clinical trials.
This 22 year old non-smoking white female subject had symptoms of leg pain prior to the vaccination (11/15/02), and was seeing a masseur for this complaint. She was also on hormonal contraceptives. The subject was vaccinated with her first dose of Gardasil on -------. On --------, Day 19 Postdose 1, the subject experienced suspected deep vein thrombophlebitis (DVT) of the left leg and consulted her own general practitioner. On --------, Day 20 Postdose 1, the subject experienced severe chest pain and was taken to the emergency room (ER). The subject subsequently experienced a suspected acute massive pulmonary embolism of severe intensity and was admitted to the intensive care unit (ICU). Echocardiography was performed and showed normal aorta and no thrombosis in the vena cava. Abdominal ultrasound was performed with no abnormal findings. On the same day, the subject died of acute massive pulmonary embolism and deep vein thrombosis of the left leg. The autopsy report confirmed the diagnosis of acute massive pulmonary embolism and deep thrombophlebitis of the left leg and also revealed an incidental finding of acute ischemic renal failure.
As this account suggests, the CBER review eventually explained away this death as a coincidence, an unfortunate side effect of taking birth control pills in a situation where the victim suffered from a pre-existing condition. So as soon as reports of similar deaths began entering the VAERS system, the CDC found ways to dismiss comparable cases such as Brooke Petkevicius by pointing a finger at birth-control pills as well. In a June 2007 report on the early deaths from Gardasil that were reported to the Vaccine Adverse Event Reporting System (VAERS), CDC dismissed Brooke’s death as yet another coincidence. “Preliminary data indicate that the two women [including Brooke], who died of blood clots were taking birth-control pills, and blood clots are a known risk associated with birth-control pills. All four deaths are being fully investigated but none appear to be caused by vaccination," claimed CDC. With regard to Gardasil, CDC wrote in its defense, "Since more than 5 million doses have been distributed, some deaths will occur coincidentally following vaccination (but not due to vaccination)."
Blaming the victim and citing coincidental death following vaccination are two well-known tactics that long ago became part of the DHHS playbook and CDC is not alone in deploying this tactic. In addition to the pulmonary embolism described above, the CBER review dismissed the two other cases of sudden death following Gardasil. One such case was a 15-year old boy who died of a heart attack less than a month after his first dose of Gardasil; yet CBER reported “the autopsy was inconclusive, but there was a strong family history of arrhythmia.” The other case was a 21 year-old woman who died with a convulsion four days after her third Gardasil dose; the CBER review again blamed this victim for her death, reporting that “this subject had a history of seizure disorder and anxiety. She suffered a seizure 4 days after dose 3, and was noted to have cocaine in her urine.”
Natural skepticism aside, making sense of individual cases like the ten public death reports and the three sudden deaths in the Gardasil trials is tricky business. Without intensive medical investigations one may never find definitive proof of harm from Gardasil. And, of course, the vast majority of Gardasil recipients have survived their vaccination series with no discernible lasting effects. There can be little dispute, however, that Merck has an enormous incentive to downplay obstacles to a profitable new product like Gardasil. And unfortunately, as we’ve seen in the clinical trial cases, FDA appears to have shared Merck’s bias, acting more like an equity participant in a DHHS “public-private partnership” than a conscientious guardian of the public trust; Its CBER reviewers effectively turned a blind eye to troubling signals as they granted Merck its BLA for Gardasil. Inevitably, however, a persuasive critique of vaccine safety monitoring for a blockbuster vaccine like Gardasil needs to move away from the realm of anecdote and into the realm of statistics. As we move beyond the review of individual cases, we’ll take a closer look at whether or not DHHS officials displayed notable biases in their analyses of Gardasil’s adverse effects in larger populations and how those analyses have been criticized by others.
Lack of diligence in postlicensure safety surveillance
Responsibility for what public health officials call “postlicensure safety surveillance” falls to a small set of DHHS departments. Two of these are the FDA’s Vaccine Safety Branch (VSB) and the CDC’s Immunization Safety Office (ISO). After CBER approves a vaccine and ACIP recommends it, the baton within DHHS passes next to VSB and ISO. In the passing of this baton, as stipulated previously, the presence of a conflict of interest does not mean that regulatory activity will necessarily reflect bias, negligence or lack of diligence on the part of the next group of regulators: Each department’s work deserves to be judged on its own merits. But in light of what appears to be a clear pattern of bias in the prelicensure activities of DHHS, it’s reasonable to approach an assessment of postlicensure activities with some skepticism. What, then, does the public record of postlicensure surveillance activity say about the presence of absence of bias and how VSB and ISO have done their jobs in assessing Gardasil’s safety?
The main public output of the FDA and CDC groups’ work has so far come in a single report published in the August 19, 2009 issue of the Journal of the American Medical Association (JAMA). In that paper, ISO’s Barbara Slade and four of her colleagues from CDC joined together with seven FDA colleagues to publish the first-ever analysis of the VAERS data on Gardasil. Not surprisingly, the JAMA paper gave Gardasil a free pass; in the process the authors joined the chorus of DHHS celebration for the breakthrough of its home-grown anti-cancer vaccine. “Vaccination with [Gardasil] has the potential to decrease the global morbidity and mortality of HPV-associated diseases, including cervical cancer. After hepatitis B vaccine, which can prevent liver cancer, [Gardasil] is only the second vaccine licensed with an indication to prevent cancer.” And although they acknowledged the possibility of injury due to blood clots like those that killed Brooke Petkevicius, Slade et al argued that the data from VAERS led to the same conclusion as the positive review from their colleagues at CBER. “The postlicensure safety profile presented here is broadly consistent with safety data from prelicensure trials.”
As for the specific question of Gardasil deaths, Slade et al acknowledged that there had been deaths associated with Gardasil. But they dismissed the VAERS death reports as not frequent enough to worry about.
Causes of death included 4 unexplained deaths, 2 cases of diabetic ketoacidosis (1 complicated by pulmonary embolism), 1 case related to prescription drug abuse, 1 case of juvenile amyotropic lateral sclerosis, 1 case of meningoencephalitis (Neisseria meningitidis serogroup B), 1 case of influenza B viral sepsis, 3 cases of pulmonary embolism (1 associated with hyperviscosity due to diabetic ketoacidosis), 6 cardiac-related deaths (4 arrhythmias and 2 cases of myocarditis), and 2 cases due to idiopathic seizure disorder. The PRR [statistics speak for “proportional reporting ratio”, or the VAERS death rate relative to the “background” expected death rate] for deaths in 6- to 17-yearolds was 1.4 (Χ2=0.42, P=.52). The PRR for deaths in 8- to 29-year-olds was 1.2 (Χ2=0.01, P=.92). Neither of these met the screening criteria for signal detection. [emphasis added]
Criticism of the JAMA analysis came quickly (some preceded the paper’s publication) and from several different quarters. One of the most trenchant attacked the relevance of the VAERS case data itself and came from the parents of a Gardasil victim. Like so many parents of vaccine injured children, Jennifer Tetlock’s parents had become deeply dissatisfied by the diligence of federal officials in evaluating Gardasil’s safety. Jennifer’s adverse reaction, as originally diagnosed, was among the least common adverse events; Slade et al reported it as an isolated case. But in April 2009, Jenny’s parents publicly voiced their suspicion that their doctor’s original diagnosis of juvenile amyotrophic lateral sclerosis may have been misleadingly narrow. They argued that “world-class immunologists suspect that Jenny had a potentially treatable autoimmune disorder mimicking ALS, possibly triggered by the Gardasil vaccination.” If true, this interpretation of her reaction placed Jenny’s death in a broader category of a severe autoimmune reactions from Gardasil. As reported previously in part 2, this kind of autoimmune reaction was a risk that the clinical trials showed to be quite common.
More broadly, Jenny’s parents struck out at CDC’s failure of postlicensure diligence.
The CDC does not inspire confidence, so we conducted our own shoestring search to determine whether Jenny was alone. We created a website (jenjensfamilyblogspot.com). Although this website has only drawn 40,000 visitors, it has out-performed the federal government in finding girls ominously similar to Jenny (current score is: Jenny site 2; CDC’s VAERS: 0).
One does not need to be a statistician to see how unlikely it is that these two other girls are the only cases out there—or how frightening it is that we already know of three documented cases of girls (those two plus Jenny) who developed ALS within several months after their vaccinations. After all, if the odds of ALS in teenaged girls are 1 in 3 million and we found 3 in only 40,000, it is very possible that many other of the 6 million girls vaccinated have already developed severe neurological collapse, like Jenny.
Jenny’s parents may have been uncertain about the proper diagnosis of Jenny’s reaction, but they were not alone in their criticism of the statistics underlying the FDA/CDC analysis. In a December 2009 letter to JAMA, Drs. Vicky Debold (Full disclosure: Debold is a director of the Age of Autism sponsor SafeMinds) and Eric Hurwitz criticized the Slade analysis. Debold and Hurwitz identified numerous flaws in the CDC/FDA report, arguing that: a) cases of autoimmune diseases such as Guillain-Barré syndrome were systematically underreported; b) the method for obtaining background rates of disease could include vaccine injury and were thus inappropriate to use in comparisons; and c) the denominator for the case population used to generate the PRRs was grossly overstated. On the last point, Debold and Hurwitz noted that Slade et al had mistakenly used “total vaccine doses distributed” as the denominator for disease rates instead of doses administered (or for that matter the number of women receiving doses), a choice that “systematically inflates the ratio’s denominator.”
Debold and Hurwitz noted the larger policy problem created by these failures in postlicensure surveillance and by Slade et al’s low standard of diligence. “Federal officials have cited this study as evidence that [Gardasil] ‘is a safe and effective vaccine,’” they noted. “However, we consider that conclusion to be unwarranted because the study draws inferences from data likely to be systematically biased.”
Diane Harper, one of the researchers involved in the Gardasil trials, agreed with Debold and Hurwitz. In an August 2009 interview with CBS News reporter Sharyl Attkisson, she also criticized Slade et al, arguing to Attkisson that “the risks of vaccination are underreported in Slade's article, as they are based on a denominator of doses distributed from Merck's warehouse. Up to a third of those doses may be in refrigerators waiting to be dispensed as the autumn onslaught of vaccine messages is sent home to parents the first day of school. Should the denominator in Dr. Slade's work be adjusted to account for this, and then divided by three for the number of women who would receive all three doses, the incidence rate of serious adverse events increases up to five fold" [emphasis added].
Harper also agreed with Jenny Tetlock’s parents’ suggestion that Slade et al were understating the number of deaths in their risk assessment, the numerator. Harper told Attkisson, "Parents and women must know that deaths occurred. Not all deaths that have been reported were represented in Dr. Slade's work, one-third of the death reports were unavailable to the CDC, leaving the parents of the deceased teenagers in despair that the CDC is ignoring the very rare but real occurrences that need not have happened if parents were given information stating that there are real, but small risks of death surrounding the administration of Gardasil."
So how should one weigh the net impact of all these claims and criticisms? Certainly, although there are serious health risks, including death, associated with Gardasil, there are also potential benefits, including reduced rates of cervical cancer. Slade’s analysis doesn’t provide the number of individuals receiving vaccine in the first two years after the Merck vaccine’s introduction, but based on the statistics she provides, it’s reasonable to assume that something less than 10 million young women received doses of Gardasil (23 million doses distributed with a target of 3 doses per subject). A balanced review of the overall benefits of Gardasil would compare the frequency and consequences of vaccine injury in this population, based on the most objective rate of adverse events, with the vaccine’s purported benefits.
If we compare the death rate (these rates were calculated in part 2 of this series) in the Gardasil trial group of 8.5 per 10,000 to an expected death rate in young women of 3.9 per 10,000, we get an extra death risk from Gardasil of roughly 4-5 per 10,000 annually. Applied to a population of 4 million young women per year, that would come to a total of close to 2,000 extra deaths per year that were caused by Gardasil during the period of its launch. This is an extraordinarily high rate and may possibly be explained away by bad luck and coincidences, as the CBER review contended. But it is the only active surveillance analysis ever done on a population exposed to Gardasil. By contrast, the calculated death rate from VAERS reports gives a much lower number, over 100 times lower, a ratio that many consumer advocates (and certainly Jennifer Tetlock’s parents) believe reflects more on the poor quality of the VAERS database than the actual risk of death from Gardasil.
But if Gardasil is successful in preventing deaths from cervical cancer, is it possible that society is still coming out ahead overall? The America Cancer Society estimates that there were 4,000 deaths in 2009 from cervical cancer. If Gardasil could prevent a significant number of these deaths in the future, then it’s possible that the benefits of the vaccine might exceed the risks. Unfortunately for the vaccine program, the deaths caused by Gardasil are immediate and the preventable deaths from cervical cancer are many years away.
Unfortunately for the public, in assessing the reliability of any estimates of Gardasil’s future benefits there are many unknowns: we don’t know how long the immunity against HPV will last; we don’t know whether costly booster shots and a new round of adverse events will be necessary; and, most important of all, we don’t yet have any idea whether or not Gardasil will succeed in preventing a meaningful number of cervical cancer deaths. We know it provides effective immunity against two of the most common cancer-causing strains of HPV. But it’s entirely possible that, just as soon Gardasil suppresses these strains of HPV, new cancerous strains will arise to take their place leaving overall cervical cancer rates unchanged. The dirty little secret of the war on cervical cancer is that public health officials have no current way to judge how and whether widespread vaccination with Gardasil will affect the actual rate of cervical cancer and they won’t be able to make that judgment for many years.
A similar situation holds in the case of a similarly multi-strain infection and its associated vaccine formulation: in this case the many different strains of streptococcus pneumoniae, the bacterial species responsible for invasive pneumoccoal disease (or IPD) and the so-called pneumococcal vaccine. In order to combat IPD, a leading cause of bacterial meningitis, a multi-strain vaccine called Prevnar was introduced by Wyeth in 2000. Prevnar quickly became one of the most commercially successful vaccines of all time, bringing in nearly $3 billion in revenue in 2008. But in asking whether Gardasil will actually work against cervical cancer, it’s useful to ask whether a similar vaccine product like Prevnar has been successful in actually preventing IPD?
A recent study from Massachusetts on its effectiveness suggests that Prevnar, contrary to all expectations, did not reduce the incidence of IPD in the state. Instead, although the forms of IPD caused by strains in the vaccine went down after Prevnar’s introduction, IPD cases caused by other strains (some of which were even more dangerous than the original strains) rose almost immediately and in opposite proportions, to keep the rate of IPD in Massachusetts constant. In plain language, Prevnar, the most commercially valuable vaccine in history, created no health benefits whatsoever. It just didn’t work.
Will this be the case with Gardasil? We will only know with any certainty what Gardasil’s benefits will be after many years, even decades of use. Right now, it’s too early to tell how many of the 4,000 annual deaths from cervical cancer might be prevented. But several things are clear in the near term: Gardasil has already injured an unknown number of young women, with these injuries likely including deaths that may number in the hundreds, possibly (based on the only data available) as many as 2,000 per year; Gardasil also has left many more young women with crippling chronic conditions like Guillain-Barré syndrome, arthritis and autoimmune thyroid conditions.
Diane Harper has also argued that assessments of the net benefits of Gardasil have overstated its value. She told Sharyl Attkisson in her interview that, "the risks of serious adverse events including death reported after Gardasil use in the JAMA article by CDC’s Dr. Barbara Slade were 3.4/100,000 doses distributed.” This rate is substantially lower than our estimates here. Nevertheless, Harper remained concerned that Gardasil’s risks outweighed its benefits. “The rate of serious adverse events is on par with the death rate of cervical cancer. Gardasil has been associated with at least as many serious adverse events as there are deaths from cervical cancer developing each year.”
In light of the many years required to prevent cases of cervical cancer, it’s clear that the current cost of Gardasil outweighs its current benefit. Moreover, it may take many years to realize any net benefit to society from Gardasil; the crossover point where realized benefits exceed the costs incurred is far away and uncertain. At the moment, therefore, there is only one net benefit that is certain: the benefit to Merck’s bottom line. And, of course, the bottom line of Merck’s business partner at NIH.
Revolving door culture
DHHS has a clear conflict of interest with respect to Gardasil at the institutional level since it shares directly in Gardasil’s profits. We’ve also seen now that this conflict of interest is echoed by (and possibly sustains) a pervasive pattern of regulatory bias in favor of Gardasil during multiple stages of the decision process. But as the Gardasil body count rises, one natural question one might ask is why, at a personal level, more DHHS officials haven’t taken the principled stand of Diane Harper, who spoke up against the ACIP Gardasil recommendation because “I want to be able to sleep with myself when I go to bed at night.”
In the case of several senior officials involved in overseeing key DHHS decisions during the Gardasil era, some portion of that answer is provided by their subsequent career moves. Indeed, these moves reveal a cultural problem that is in many ways more troubling than the direct Gardasil financial conflicts: a pervasive pattern of senior officials cashing in on their careers in public service in order to obtain lucrative corporate and consulting jobs. The career moves of these senior officials show that a virtual revolving door between regulators and the pharmaceutical, vaccine and biologics companies they are supposed to regulate erodes any meaningful sense in which these officials truly serve consumer interests, especially when it comes to product safety. This revolving door provides the cultural foundation that undergirds some of the more egregious institutional conflicts.
A short account of the recent careers of just a few of the officials involved in regulating Gardasil shows this revolving door in action.
• Mike Leavitt was named on December 13, 2004 as Secretary of DHHS, where he subsequently was responsible most of the critical regulatory decisions involving Gardasil. In January 2009, he left HHS and formed Leavitt Partners, a Washington DC consulting firm that helps its client “enter new markets, enhance the value of their products and navigate dynamic regulatory and reimbursement systems.” In his consulting work, Leavitt could certainly teach his clients about Gardasil and how they could follow Merck’s example in forging a model “public-private partnership.”
• Julie Gerberding was named Director of CDC on July 3, 2002 and served in that role until she resigned on January 29, 2009. Gerberding watched over Gardasil policy at CDC during the period of FDA review in which ACIP put Gardasil on a fast track for approval in June 2006. She also was in charge of the oversight for CDC’s postlicensure safety activities during much of the period leading up to Slade et al’s JAMA submission when portions of the VAERS analysis were reviewed with ACIP. Less than a year after leaving public service, on December 21, 2009, Merck announced Gerberding’s appointment as President of the Merck Vaccine Division, effective January 25, 2010, the minimum interval allowed for a Federal official to assume a position at a company they used to regulate. Gerberding, who once regulated Gardasil, is now directly responsible for its growth and profitability.
• Karen Goldenthal was the Director of the Division of Vaccines and Related Products Applications within CBER, the FDA division responsible for approving Gardasil’s BLA in June 2006. In 2007, shortly after Gardasil’s approval, Goldenthal left CBER to become Executive Director of PharmaNet Consulting. PharmaNet is “a global, drug development services company, provides a comprehensive range of services to the pharmaceutical, biotechnology, generic drug, and medical device industries.” Other FDA executives have taken leadership positions at PharmaNet, including William Egan, former head of Vaccine Research and Review at FDA, now a Vice President in PharmaNet’s consulting practice.
These departures provide just a few small examples of a pervasive exodus of FDA officials, many of whom leave FDA in order to provide advice to pharmaceutical companies on how to make their way successfully through the pre- and post-licensure processes. And when it comes to vaccines, there is a specific market for former CBER officials to coach vaccine manufacturers on how to get their BLAs approved and their launches more profitable. Like PharmaNet, a consulting company called the Biologics Consulting Group (BCG) shows how active the revolving door between FDA and industry has become. Here’s how BCG describes itself.
Biologics Consulting Group, Inc. (BCG) is a team of consultants who provide national and international regulatory and product development advice on the development and commercial production of biological, drug and device products. Our staff consists of experts in regulatory affairs, product manufacturing and testing, pharmacology/toxicology, facility inspections, statistics, program management, and clinical trial design and evaluation. Many of our consultants are former CBER, CDER, and CDRH reviewers. [emphasis added]
In an environment so stepped in both direct and indirect conflicts of interest, is it any wonder that Gardasil regulators have leaned so steeply in favor of industry while overlooking serious safety concerns?
The early victims of Gardasil look for justice
The final phase of regulatory activities surrounding Gardasil have yet to play themselves out. These involve the process of adjudicating claims of injury and death due to the vaccine. The DHHS agency responsible for this work is the Health Resources Services Agency (HRSA), which houses the Division of Vaccine Injury Compensation, the group responsible for managing the Vaccine Injury Compensation Program (VICP), more commonly known as “vaccine court.” In light of the pattern of bias we’ve observed in the approach other DHHS agencies have taken to Gardasil, one might reasonably question the prospects for fair treatment of Gardasil victims in vaccine court. Can we really expect the director of HRSA to encourage a fair and generous compensation policy on Gardasil when her colleagues over at NIH are profiting from the patent license, CDC is actively promoting its use and her former colleagues at FDA are providing consulting services to companies helping them avoid regulatory pitfalls and keep their profits intact?
As in the case of its sister agencies, the presence of conflict of interest does not necessarily mean that HRSA will demonstrate bias, negligence or failures of diligence in their approach to Gardasil. In advance of any record of decisions, however, it’s simply too early to tell how HRSA will respond. In other controversial areas such as the Autism Omnibus Proceeding, petitioners have been deeply disappointed in their treatment at the hands of the vaccine court. And it seems likely that Gardasil families are destined for their own day in vaccine court: HRSA provides “table injuries” that provide compensation for a short list of outcomes on a few vaccines, but there are no table injuries yet specified for Gardasil. (HRSA has commissioned the Institute of Medicine to develop such a list for the entire category of HPV vaccines. A candidate list of injuries can be found in the latest working list from the “Committee to Review Adverse Events of Vaccines”, see HERE ) So as Gardasil petitioners find their way into the VICP process, HRSA officials will be setting Gardasil injury compensation policy for the first time.
And the Gardasil girls are coming to seek justice. In an early action, on March 13, 2010, the parents of Jennifer Tetlock filed the following petition with the VICP.
The above captioned Petitioners request compensation under the National Vaccine Injury Compensation Program, 42 U.S.C. 300aa-10 et seq. (Supp. 1996), for the death of minor, Jennifer Tetlock who received the third series of the Gardasil vaccination on March 1, 2007 from James Cuthbertson, M.D. in Berkeley, California and thereafter suffered from atypical amyotrophic lateral sclerosis (ALS)-like lower motor neuron disease which was caused in fact by the above stated vaccination.
Will Jennifer Tetlock receive justice? It’s hard to imagine how any agency so inextricably linked to the Gardasil program--from invention to approval and recommendation to protection and profit—can possibly be trusted to be a fair arbiter of guilt and innocence.
But one can always hope. After all, the guardians of vaccine safety in DHHS have children themselves. And like Diane Harper, they also need to sleep with themselves when they go to bed at night.
in Mark Blaxill, Vaccines | Permalink
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