Saturday, June 30, 2012

Ireland preserves Democracy, Scraps E-Voting Machines/ The Independent

From the Irish Times:

In a final vote of no confidence, Ireland’s ill-fated e-voting machines are finally headed to the scrap heap.

From the June 29 Independent:

THE Government has sold the infamous €54m e-voting machines for scrap -- for €9.30 each. [Sold as scrap for about 15 cents per ten dollars spent on their purchase.]
A huge fleet of trucks will begin removing the 7,500 machines from 14 locations on Monday.
They will be taken to a Co Offaly recycling company, KMK Metals Recycling Ltd in Tullamore, where they will be stripped down and shredded.
Ironically, the owner of the firm, Kurt Kyck, cast his vote on one of the machines in the 2002 elections. He has now paid €70,000 for the lot.
Scrapping the machines brings to an end the embarrassing e-voting debacle which has cost the taxpayer more than €54m since it emerged the expensive equipment was faulty. 
They could not be guaranteed to be safe from tampering. And they could not produce a printout so that votes/results could be double-checked...
But the voting machines still being used in the USA have identical problems. Even the Voice of America has reported on the ease of hacking our votes.  
"We believe that a very resourceful 12 to 13-year-old would be able to essentially produce these alien electronics that can hijack the machine," said Roger Johnston.  Roger Johnston heads up Argonne National Laboratory’s Vulnerability Assessment Team.
"I think our view of the voting machines we’ve looked at is that there really isn’t much security thought put into these devices," he said.
Johnston says security concerns are not isolated to the way the machines are made. 
"Often the warehouses where these machines are stored have fairly weak security, but almost universally, these machines are transported by third party low bid trucking companies, where there’s no background checks on these individuals," said Johnston. "Often the machines arrive at a polling place and there’s no one to sign for them or to take responsibility for their oversight.  So there’s often quite a period of time when these machines could be tampered with." 
ABC News covered this topic in 2006:

Princeton University researchers using an Accuvote TS -- a touch screen version of the Diebold machine -- showed how easy it would be to deploy a virus that would, in seconds, flip the vote of any election...
"We're taking the vote-counting process and we're handing it over to these companies -- and we don't know what happens inside these machines," said Edward Felten, a professor and a researcher at Princeton's Center for Information Technology Policy, which ran the study...
Machines malfunctioned in Texas, where 100,000 votes were added.
In California, directions for voters with vision problems came out in Vietnamese.
And in Maryland, screens froze and memory cards went missing.
Gov. Robert Ehrlich, a Republican running for reelection, advised residents to vote by absentee ballot because he had no confidence in the machines.
"I don't care if we paid half a billion dollars or $1 billion," Ehrlich said. "If it's going to put the election at risk, there's no price tag for a phony election or a fraudulent election..."

Wednesday, June 20, 2012

Anthrax Vaccine Manufacturer, with no expertise and no new products after 14 years in business, gets $220 million grant to develop nuclear, chemical, radiological and biological countermeasures for the US government/ Biz Journals

The Gang who Couldn't Shoot Strait at Emergent BioSolutions gain more largesse from the USG.  Yet this company cannot do anything right except obtain government contractskill off the competition, co-opt watchdog nonprofits and set up their own education agencies. See "Anthrax Vaccine:  to the Victor the Spoils"

"This award underscores Emergent’s core competencies not only in product development and manufacturing,  [They have developed no products--Nass] but also our expertise in contracting with the U.S. government and navigating the regulatory process," CEO Daniel J. Abdun-Nabi said in a statement.

From BizJournals:

Rockville-based Emergent BioSolutions Inc has formed a public-private partnership with the Department of Health and Human Services to establish a Center for Innovation in Advanced Development and Manufacturing.
The contract has an initial run of eight years worth $220 million with up to 17 additional one-year options. The partnership, with HHS’s Biomedial Advanced Research and Development Authority [BARDA], will initially develop a new pandemic influenza vaccine and construct facilities to produce it.
It will also develop chemical, biological, radiological and nuclear medical countermeasures.
Emergent (NYSE: EBS) announced the partnership shortly before the markets closed Monday. Its stock gained 77 cents, or 5.6 percent, in late-day trading and closed at $14.41 per share.
From Scott Lilly, former staff director of the House Appropriations Committee,  who wrote a report on Emergent BioSolutions' financial whiz-bangery in 2010:

... A report I recently completed for the Center for American Progress examines one particular set of contracts involving the purchase of a vaccine for exposure to Anthrax.  Normally it is virtually impossible to estimate the profit margin that a government contractor is making on a particular contract with information available in the public domain.  This contract was different, however, because the contractor was a public corporation which had only one product and only one customer.  Because the Securities and Exchange Commission requires disclosure of revenues and expenditures to stock holders,  it is possible to see how much it cost the company to produce what it was selling to the federal government. 
In the Form 10K released by this contractor in March,  the company disclosed that its revenues for the sale of its vaccine totaled $217 million.  The cost of sales according to the report was only $46 million.  Further research indicated that the company has enjoyed such margins for nearly a decade with sales exceeding $1.3 billion and expenses of less than $0.3 billion.
The company, Emergent BioSolutions,  argues that such margins are justified because it has faced a high level of financial risk in being a provider to the government.  But an examination of the risks it has faced since its founding in 1998 turned up a remarkable lack of risk compared to almost any other type of commercial endeavor.  The vaccine which is now sold under the name of BioThrax was developed by the U.S. Army in the 1960s.  The license to manufacture the vaccine was obtained by the state of Michigan and the state also built the facilities used for manufacture.  Those facilities were bought by Emergent with a down payment of $2.25 million.  They were then upgraded almost entirely at the expense of the U.S. government. 
The price of the vaccine was raised from a little less than $3 a dose which the government was paying to the state of Michigan to $10.60 a dose after Emergent took over. The price was then inexplicably raised again to more than $27 a dose—yielding the enormous profit margins detailed in the company’s annual report.  To protect those hefty margins, Emergent has probably the largest and most expensive lobbying team in Washington when lobby expenditures are compared to company revenues. 
We don’t have any idea how many high profit margin contracts the government has and it is only a result of the rather odd business model of this company that its high margins were uncovered.  Annual reports for companies that have multiple products and sell to customers other than the government ordinarily yield little information that would permit an estimation of the markup they get out of their government sales...  

Sunday, June 17, 2012

Clinical Trial Ethical Underpinnings: reflecting on a pediatric anthrax vaccine trial / Sci Am Blogs

In her third excellent Scientific American blog post, Infectious Disease doctor Judy Stone has delved into the ethical and regulatory framework under which clinical research must be conducted.  Dr. Stone provides a succinct historical overview of the important documents, and how they were enshrined in regulations guiding the conduct of research in humans.  For readers unfamiliar with The Declaration of Helsinki, the Belmont Report, and the Nuremberg Code, this is important information.  Did you know that informed consent is a relatively new, post World War II phenomenon?

The addition of children as routine research subjects is even newer, dating back only 10-15 years.

Given this context, Dr. Stone explores how the proposed trial of pediatric anthrax vaccine fails to comply with the existing norms and regulations:
... How does the proposed pediatric vaccine trial fit with the precepts outlined above? 
First, the Belmont principle “respect for persons” is violated, in that this vaccine trial, using the adult anthrax vaccine (AVA) has known serious risks and other potentially unknown risks in kids, and no benefit. We won’t even know if any antibodies formed would be protective.

Belmont principle of benefits to the participant is violated since there are none. Furthermore, U.S. regulations (45 CFR 46, Subpart D) state that children may not be exposed to risk if a medical experiment does not offer them a direct benefit. Even the NBSB report notes “Currently, U.S. children are not at immediate risk from anthrax and would not benefit directly from pre-event AVA [anthrax vaccine] administration”…There is only the potential future benefit...

And it appears that the Belmont principle of justice will be violated. A vulnerable population will be used without assent. (How many kids would willingly take a painful course of five injections, even without worry of other side effects?) How will the children’s continued participation be ensured? Coercion? Or bribes? Reportedly, the study is to be done in New York City, where there are 9/11 first responders who would be willing to volunteer their children. These parents, traumatized by 9/11, are unlikely to be able to review an informed consent form critically or objectively. Would there be such enthusiastic parents in rural America? I doubt it. I like the biting suggestion by Dr. Anthony Robbins, “How about the children of people who have the national security clearance required for the government to share with them all the evidence that adds up to a “credible threat?” With that information in hand, these parents would be able to make the choice-an informed decision for their children-that the rest of the public surely cannot.” ...

Skewed Results? Failure to Account for Clinical Trial Drop-Outs Can Lead to Erroneous Findings in Top Medical Journals / BMJ

Unmanned satellite-aircraft devices can now stay in orbit more than a year, then return to earth and make a soft landing at a military base!  Just imagine the accuracy and precision of the measurements and analysis needed to achieve this.  This accomplishment deserves more than a hat-tip to the scientific method.

Yet when it comes to medical research, arguably as important to the well-being of citizens, accuracy and precision are nowhere in sight.  Results of studies are all over the map.  Some researchers best distinguish themselves by the clever ways they can transform any set of results into support for whatever drug, device or vaccine their sponsor wants to sell.  Imagine if they were rocket scientists!

I have previously discussed about ten methods that have been used to squeeze an ill-fitting conclusion from a clinical dataset.  One such method:  the handling of subjects "Lost to Followup" has now been shown to skew the results of as many as one third of clinical trials published in top medical journals, according to an open-access article in the May 18, 2012 BMJ by Akl EA et al.  Akl's group examined 235 papers in 5 top medical journals for whether losses to followup were mentioned, and how the losses were handled.  Over half the authors of the 235 papers (54%) did not respond to questions from Akl's group regarding details of the research, which is troubling.

Nineteen per cent of the trials did not mention how losses to followup were being handled.  Of those papers that did mention losses to followup, generally 2-15% of total subjects were lost.

When reasonable assumptions about these losses were made, it was found that the conclusions of the trials could become nonsignificant in about 1/3 of cases.  In other words, the positive result would be lost.

From the SUNY Buffalo press release:
“We found that in up to a third of trials, the results that were reported as positive – in other words, statistically significant – would become negative – not statistically significant, if the investigators had appropriately taken into consideration those participants who were lost to follow-up,” says Elie A. Akl, MD, MPH, PhD, lead author, and associate professor of medicine, family medicine and social and preventive medicine at the University at Buffalo School of Medicine and Biomedical Sciences and School of Public Health and Health Professions. He also has an appointment at McMaster University
“In other words, one of three claims of effectiveness of interventions made in top general medical journals might be wrong,” he says.
In one example, a study that compared two surgical techniques for treating stress urinary incontinence found that one was superior. But in the analysis published this month, it was found that 21 percent of participants were lost to follow-up. “When we reanalyzed that study by taking into account those drop-outs, we found that the trial might have overestimated the superiority of one procedure over the other,” Akl says.
According to Akl, it has always been suspected, but never proven, that loss to follow-up introduces bias into the results of clinical trials. “The methodology we developed allowed us to provide that proof,” he says.
The methodology that he and his coauthors developed consists of sensitivity analyses, a statistical approach to test the robustness of the results of an analysis in the face of specific assumptions, in this case, assumptions about the outcomes of patients lost to follow-up.

Friday, June 1, 2012

Narcolepsy traced to specific vaccine batches/ The Local

Very interesting:  the Narcolepsy Association discovered that specific lots were involved, after the Swedish Medical Products Agency denied it.  Bad lots may mean that the regulators were not doing their job.  If this devastating narcolepsy epidemic was caused by bad lots, liability for the injuries might land on the manufacturer, in this case GSK.  From Sweden's The Local:
A new Swedish study shows that all Swedes who developed narcolepsy from the swine flu vaccine Pandemrix received the vaccine from 12 of the 35 batches, despite the Swedish Medical Products Agency’s (Läkemedelsverket) previous claim that no such connection exists.

“We will have to think again,” said Maria Szirmai of the Swedish Medical Products Agency to newspaper Göteborgsposten (GP).

Over 220 Swedes, most of them children, developed narcolepsy as a side effect from the Swine flu vaccine Pandemrix, according to the reports filed with insurance company Läkemedelsförsäkringen.

All these had received the vaccine from some 12 of the 35 batches of vaccine delivered to Sweden.

From 23 of the 35 shipments there is no recorded case of anyone developing the condition, according to the study, which was carried out by the Swedish Narcolepsy Association (Narkolepsiföreningen).

The association traced the vaccine through the batch number on the side of the boxes.

Their findings will now be investigated by the agency, which has previously denied any connection between different vaccine shipments and the onset of narcolepsy.

In some parts of Sweden, namely in counties Skåne, Västra Götaland, Dalarna and Uppland, there are more children affected by narcolepsy than anywhere else in the country, which has so far flummoxed researchers.

Over half a million Swedes were vaccinated against swine flu with Pandemrix between autumn 2009 and spring 2010.

Anthrax vaccine – To the victor, the spoils / Scientific American blogs

From infectious disease MD Judith Stone at Scientific American comes this comprehensive look at what is behind the push to keep buying anthrax vaccine and even give it to children:
In my last post, we began to play “Follow the Money” to better understand the history of the anthrax vaccine and the current proposal to test the vaccine on children. 
Conflicts of Interest-Case Study 
Major issues with the anthrax vaccine include safety, conflicts of interest and the lobbying power of the drug developer. I don’t have all the answers, but will outline some of the concerns. Some of these are voiced by ardent vaccine opponents, such as NVIC; others sound more akin to “conspiracy theorists.”  
A list of safety concerns is presented by two ex-officers in the National Guard. Counterarguments as to safety issues are given by the Institute of Medicine and were outlined in the first part of this series. 
Earlier, Steve Salzberg pointed out the conflicts of interest with advisory committee members who receive their funding from government biodefense contracts. But let’s look at the sole manufacturer of the country’s vaccine. 
The anthrax vaccine was initially developed by the state of Michigan’s Biologic Products Institute (MBPI). In 1998, the MBPI plant was closed for “renovations” coincidentally following an FDA “notice of intent to revoke licenses”. MBPI was sold in 1998 to for-profit BioPort corporation, which became a subsidiary of Emergent BioSolutions. 
According to the Department of Defense’s anthrax vaccination website, Emergent is headed by Fuad El-Hibri and Admiral William Crowe, Jr., a former Chairman of the Joint Chiefs of Staff (appointed by President Reagan) and the U.S. ambassador to Britain (1994-1997, appointed by President Clinton). El-Hibri was “CEO of the British company Porton International, which had made a fortune selling anthrax vaccine to countries like Saudi Arabia during the Gulf War.” El-Hibri was not a U.S. citizen at the time and there was reluctance in some quarters to have the government’s sole anthrax vaccine supply controlled by foreign nationals. So Crowe was brought in as director in exchange for about 10% of the company’s stock
The Corporate Research Project details the bailouts to BioPort to keep the company, the sole manufacturer of anthrax vaccine, viable following considerable regulatory and financial problems. 
“BioPort had originally been awarded a $29.4 million DoD contract to supply 8.7 million doses of anthrax vaccine at the price of $4.36 each. But in 1999, the company got a $24.1 million bailout from the DoD. This included an increase in the price per dose from $4.36 to $10.64 and a reduction in the number of doses by about 30 percent. The Pentagon also agreed to advance BioPort $18.7 million to help it cover its debts. The new agreement increased the cost of the contract for the Pentagon to $49.8 million over the following five years. The government has reportedly spent more than $120 million of taxpayers’ money to keep the company afloat.” 
Reporter Bob Evans further details BioPort’s financial mismanagement, quoting Congressman Walter Jones, R-N.C., “The message seems clear: If a company wants to make millions without providing a product or service, enter into a sole-source contract with the Department of Defense to produce vaccines…BioPort appears to have the government over a barrel.” 
In addition to the financial subsidies, outlined above, concerns have been raised about irregularities in the manufacturing process. Reportedly, on the eve of the Gulf War, the Department of Defense “accelerated and altered the vaccine’s manufacturing process, but without proper regulatory approvals.” “The Government Accountability Office (GAO) reported that the manufacturer “did not notify FDA of a number of changes made in the manufacturing process in the early 1990s and no specific studies were undertaken to confirm that vaccine quality was not affected.” GAO added that the “ingredients used to make vaccine were changed from the original vaccine,” and that “prior to the time of licensing, no human efficacy testing of the … vaccine was performed.” A 2000 Congressional report stated, “use of the current anthrax vaccine for force protection against biological warfare should be considered experimental and undertaken only pursuant to FDA regulations governing investigational testing for a new indication.” 
After September 11, 2001, Bioport quickly got its license back, although the FDA had previously found a number of quality control issues in the manufacturing process.
Since then, Emergent BioSolutions has had a lucrative government monopoly and has been aggressive in protecting it. According to the Center for Responsive Politics, Emergent spent more than $3.2 million on lobbying in 2011 alone. 
There have also been public relations and “educational” endeavors sponsored by Bioport, though not always advertised as such. The Partnership for Anthrax Vaccination Education, or P.A.V.E., had a website in support of the vaccine, operated by Muhiuddm Haider, a professor at George Washington University. One of PAVE’s regular speakers was Jerome Hauer, former assistant secretary of health and human services for emergency preparedness; there was no disclosure that he was being paid by BioPort. 
Revolving Door Lobbying 
However, in 2003, while still a government employee HHS, Hauer stated that a “new vaccine was “a better long-range option than investing in expanding manufacturing capacity” for BioThrax…” and that “the scientific basis” for a genetically engineered vaccine was “very sound and will result in an improved product.” Yet as soon as he left, and became a member of BioPort’s board, as well as a lobbyist for them, his assessment changed radically as he changed masters. 
Other lobbyists included: 
Louis Sullivan, secretary of health and human services under President George H.W. Bush
McKenna Long & Aldridge (MLA), which helped BioPort win a $122.7 million Project Bioshield contract. “MLA had supplied several lawyers, including one who’d helped write the Homeland Security Act of 2002 and two who’d been tapped by Congress for help in creating the BioShield law.” 
John Hishta, former executive director of the National Republican Congressional Campaign Committee and former campaign manager for Sen. John Warner (R-Va), influential in Pentagon politics. 
A more complete list of lobbyists and spending levels are available from the terrific Center for Responsive Politics here and here. They have a handy list of former Congressmen and a wonderful “revolving door profile.” 
These lobbyists have not only helped Emergent BioSolutions secure these seemingly exorbitant government contracts, but have helped ensure that they maintain a monopoly. Their main rival was VaxGen, who had won an $877.5 million federal contract to develop a safer, genetically engineered vaccine. According to an Los Angeles Times investigation, “Fear Inc.,” “Emergent responded by mobilizing more than 50 lobbyists, including former aides to Vice President Dick Cheney, to make the case that relying on the new vaccine was a gamble and that the nation’s safety depended on buying more of Emergent’s product
The company and its allies in Congress ridiculed VaxGen and impugned the competence or motives of officials who supported the new vaccine. The lobbying effort damaged VaxGen’s credibility with members of Congress and the Bush administration.” 
Between 2004-2007, Emergent spent $5.29 million on its cadre of lobbyists, while VaxGen spent only $720,000 on six lobbyists. After VaxGen’s contract was cancelled, Emergent had the audacity to claim that their aggressive lobbying was in the country’s interest. Executive Robert G. Kramer admonished the House Government Oversight and Reform Committee, “HHS has staked the nation’s protection against the No. 1 biologic threat on an experimental product.” He further threatened the committee that, should they fund VaxGen, Emergent would have to reconsider its decision to produce the vaccine. 
Adding insult to mortal injury, in 2008, Emergent purchased Vaxgen’s recombinant anthrax vaccine technology for a bargain $2 million, given that “more than $250 million was spent to develop it.” And now Emergent has lucrative government contracts for a vaccine with the recombinant protein antigen and a third generation vaccine. 
PharmAthene is another Emergent rival and has also had a rocky road, with it’s hopes for a 2008 contract dashed when Biomedical Advanced Research and Development Authority (BARDA) cancelled plans; and Emergent again vastly outspent its rival on lobbying. 
Emergent had another reason to aggressively protect its contract. According to the Center for American Progress’ must read report, Getting Rich on Uncle Sucker, Emergent’s cost of production in 2009 was $46 million and profit $217 million—a markup of about 300%.
Also, since the vaccine only has a four year shelf life, Emergent is guaranteed a steady income stream—on the order of $100 million/year—just to replenish the stock. 
While Emergent won a grant worth up to $1.25 billion in late 2011—and which was a sole-source contract—its future monopoly is not entirely guaranteed. BARDA is supporting development of next generation recombinant protein antigen (rPA)-based vaccines that will require fewer doses and hopefully have less side effects. 
In 2004, President Bush signed Project Bioshield, which earmarked $5.6 billion for new drugs and vaccines to counter bioterrorism. At this point, we seem to have a multi-billion dollar vaccine which has never been shown to be efficacious against inhalational anthrax and was adopted by circumventing usual FDA procedures and despite numerous manufacturing quality issues and safety issues. 
And that brings us to the proposed plan for testing the anthrax vaccine in children… Coming up next. 
About the Author: Judy Stone, MD is an infectious disease specialist, experienced in conducting clinical research. She is the author of Conducting Clinical Research, the essential guide to the topic. She survived 25 years in solo practice in rural Cumberland, Maryland, and is now broadening her horizons. She particularly loves writing about ethical issues, and tilting at windmills in her advocacy for social justice. As part of her overall desire to save the world when she grows up, she has become especially interested in neglected tropical diseases. When not slaving over hot patients, she can be found playing with photography, friends’ dogs, or in her garden. Follow on Twitter @drjudystone or on her website. Follow on Twitter @drjudystone
The views expressed are those of the author and are not necessarily those of Scientific American.