Evelyn Pringle June 23, 2006
Over the past six years, ten FDA approved drugs have been withdrawn from the market due to deaths and injuries, leading lawmakers to accuse the FDA of not doing its job in protecting the public from unsafe drugs and to call for measures of improvement.
On June 20, 2006, the New York Times reported that “two influential senators are expected within weeks to introduce a legislative proposal that could drastically change how drugs are tested and approved in the United States.”
The Senators behind the proposal are Michael Enzi (R-Wy), chairman of the Health, Education, Labor and Pensions Committee, and Ted Kennedy (D-MA), the ranking Democrat on the committee.
“In broad terms,” the Times article by Gardner Harris explains, “the bill would require that drug makers disclose the results of all large human tests of their drugs, known as Phase 3 and Phase 4 trials; create a detailed risk management plan to uncover and control any safety problems that arise after a drug is approved; and pay penalties if they fail to follow through with this plan, according to four experts who were briefed on the proposals.”
However, while lawmakers search for ways to ensure that Big Pharma does not continue to conceal adverse reactions that surface during drug trials and to sever the ties between the nation’s public health officials and Big Pharma, the Bush administration continues to promote their cozy relationships and help drug companies escape accountability for misconduct.
The best example of the administration’s efforts to protect Big Pharma was revealed recently when the FDA announced a preemption rule that would disallow lawsuits in state court against drug makers if a drug has been approved by the FDA.
“We think that if your company complies with the FDA processes, if you bring forward the benefits and risks of your drug, and let your information be judged through a process with highly trained scientists, you should not be second-guessed by state courts that don’t have the same scientific knowledge,” said FDA deputy commissioner on medical and scientific affairs, Scott Gottlieb.
But in all fairness, the FDA is certainly not the only public health agency in bed with Big Pharma. Nobody can deny the fact that Big Pharma is an equal opportunity corrupter. Its obvious that drug companies have infiltrated every Federal regulatory agency in the US.
For instance, on June 14, 2006, a National Institute of Health Alzheimer’s researcher, Dr Trey Sunderland, asserted his Fifth Amendment rights, and refused to testify before the House Energy and Commerce Committee about accusations that he has profited from giving Pfizer access to spinal fluid and plasma samples collected by the NIH.
Documents presented at the hearing revealed that between 1996 an 2004, Dr Sunderland accepted consulting, speaking and advisory fees totaling about $612,000 and committee staff members estimate that about $285,000, was related to 3,245 samples taken from 538 patients who participated as volunteers at the NIH.
At a price of about $12,000 per patient, the committee estimates the cost of collecting the samples that Dr Sunderland handed to Pfizer is close to $6.5 million.
The committee also noted that he did not seek prior approval to work for Pfizer, and did not report any of the income to the agency as required by NIH rules.
In fact, at one point, when asked, Dr Sunderland said he had no outside deals. According to the December 22, 2004 LA Times, while reviewing financial disclosure reports from scientists at the NIH, in March 2000, ethics officer Olga Boikess noticed that Dr Sunderland had not declared any jobs with the industry so she sent him an e-mail that said: “You did not list any outside positions.”
To which, Dr Sunderland replied: “I do not have any outside positions to note.”
This case had been dragging on for years but the doctor has probably not been too worried because history shows that any time a Republican lawmaker get too pesky about the money trails leading to the NIH, Big Pharma simply offers enough money to induce him to jump ship.
A couple years ago, two Republicans on powerful committees switched sides shortly after they launched investigations into conflicts of interest between drug companies and employees at the NIH.
Representative, WJ “Billy” Tauzin (R-La), was chairman of the House Energy and Commerce Committee, and had cited “secret consulting fees and stock options from drug companies” as reasons to request documentation of all payments from Big Pharma to NIH scientists.
But next thing you know, Tauzin announces that he is not running for reelection, and leaves Congress to become President of the Pharmaceutical Research and Manufacturers of America, the giant trade group that represents Big Pharma, with a reported $2 million a year in salary, benefits and perks.
Next up to bat, was Representative James Greenwood (R-Pa), who led 3 hearings on NIH conflicts of interest and criticized the agency for allowing scientists to use “a swivel chair” to make decisions while taking drug company money.
But low and behold, shortly thereafter, in July 2004, Rep Greenwood announced that he was giving up his post as chairman of the Energy and Commerce subcommittee to retire, only to become President of the Biotechnology Industry Organization, a group that in the same year, urged lawmakers not to bar NIH scientists from entering into paid consulting deals.
A report by the Office of Government Ethics, released the same month that Rep Greenwood announced his “retirement,” said the NIH was beset by a “permissive culture,” and revealed that 40% of the 155 randomly selected sample payments to agency employees reviewed had not been approved or accounted for within the NIH.
The FDA remains at the top of the list for corruption simply because the FDA evaluates the safety and effectiveness of drugs and decides which drugs can be marketed in the US.
Typically, as a first step toward the approval process, a drug company will initiate laboratory testing to assess the effectiveness and safety of a drug and if the laboratory testing is successful, the company will begin testing the drug on animals. The FDA does not become involved until the drug maker seeks permission to test the drug on humans.
When the drug reaches that point, the FDA’s Center for Drug Evaluation and Research, evaluates the results of laboratory and animal testing prior to allowing any study on humans.
Once a drug is approved for testing on humans an Institutional Review Board (IRB) is appointed to review and monitor the research. An IRB is generally made up of outside scientists, doctors and other medical professionals and has the authority to approve or disapprove a study or to require modifications to secure approval of the research.
The purpose of an IRB is to assure that appropriate steps are taken to protect the rights and welfare of human subjects. To that end, an IRB uses a group process to review research protocols and materials such as informed consent documents and investigator brochures related to the research.
In recent years, serious questions have been raised regarding the impartiality of the review process due to the fact that many of the FDA advisors recommending approval of a product are at the same time employed by the drug company that developed the drug or hold some other financial interest link to the company.
Due to these conflicts of interests, critics say dangerous drugs are winning approval. For instance, nearly a third of the members of the advisory panel that reviewed the data on Vioxx, Celebrex and Bextra, and voted to allow the drugs to remain on the market, even after Vioxx had been pulled off the market, had financial ties to the makers of the drugs and had their votes not been counted, they would never have received a vote of approval.
In addition, problems continue to surface in the private research industry. Contract Research Organizations (CRO), are now hired by the industry to perform research.
Critics says the competing CROs are skewing research in favor of approval in order to win more contracts. The funding up for grabs is enormous. According to a March 24, 2006, MSNBC commentary by Arthur Caplan, director of the Center for Bioethics at the University of Pennsylvania, “Private companies running studies for pharmaceutical and device companies are now a $14 billion industry in the United States alone.”
According to John Abramson, a clinical instructor at Harvard Medical School, and author of, “Overdosed America”, “When the institutional review boards were created, most medical research was conducted by universities and nonprofit institutions.”
“Similarly,” Mr Abramson says, “oversight of the safety of human volunteers in most U.S. studies is no longer done by nonprofit IRBs, but by for-profit review companies, hired directly by the for-profit research companies.”
In his opinion, he says the system lacks the appropriate checks and balances to protect human volunteers.
In the April 6, 2006 LA Times, Mr Abramson made a shocking revelation when he said, “the FDA recently approved “phase 0 studies” in which human beings can be given minuscule doses of experimental drugs even before animal studies are completed.”
A recent case in the UK demonstrates the dangers that could occur in such a study. In March 2006, six otherwise healthy men ended up in a London hospital in critical condition after participating in the trial of a new an anti-inflammatory drug, called TGN1412, to treat conditions involving the immune system, such as leukemia, multiple sclerosis and rheumatoid arthritis, conducted by the US based company, Parexel International Corp, on behalf of the German drug maker TeGenero.
The worst affected of the six men, Mohamed ‘Nino’ Abdelhady, called the Elephant Man because of the extreme swelling of his head, on April 5th, told the Daily Mail that he is plagued by nightmares.
Still recovering in the hospital at the time, he explained what he remembered. “I started to feel ill,” he said, “almost as soon as they had finished injecting me.”
“I felt as if I had rocks on my head,” he recalled, “and I must have started hallucinating.”
“Help me,” he told the newspaper that he screamed, “I’m dying.”
Ryan Wilson, the most critically ill man, begged doctors to put him to sleep because he was in such agony. His family was warned that his heart, lungs and kidneys failed.
His sister-in-law Jo Brown, recalled the horrific moment when they saw Mr Wilson in intensive care. She told reporters that his head had swollen to nearly three times its normal size, and that his neck was the same or wider than his head and that his skin had turned a dark purple.
Mr Wilson remained in a coma for three weeks, and upon awakening, learned that he may lose parts of his fingers and toes, which had turned black because of his reaction to the drug.
“I’m told it’s like frostbite and my fingers will just fall off,” he told the UK’s News of the World recently.
In addition, Mr Wilson also suffered from heart, liver and kidney failure, septicemia, pneumonia and dry gangrene and is considered very luck to be alive, according to News Target on May 20, 2006.
The Parexel research was at the Phase I stage, where a drug is tested for safety with a small number of people who are given a tiny dose under careful supervision, not to determine whether the drug works, but to check for side effects, according to Q&A Drug trials by BBC News on March 16, 2006.
Experts say the recruitment of subjects for the Parexel trial left much to be desired. The web site that announced the recruitment hardly mentioned the potential risks, but elaborated at great length about the good pay, free food and “plenty of time to read or study or just relax, with digital TV, pool table, video games, DVD player and free Internet access.”
Parexel also recruits by placing ads online or in local papers, where critics say, they draw the attention of the young and poor. Once on the books, recruits often get automatic offers. “The offers keep rolling in via text message,” Tom de Castella, a former Parexel volunteer said in the March 19, 2006 Times Online. “$650 for three days here, $1,000 for a week there,” he said.
Ethicists shown the Parexel consent form, which is supposed to describe the experiment and its risks, told Bloomberg News, “the document didn’t sufficiently inform participants of the therapy’s possible dangers or properly depict the treatment as a novel drug that can disrupt the body’s immune system.”
The 13-page form also exploited the subjects’ need for money, they said, by threatening to withhold the 2,000 pound ($3,500) payment if the men left the test early.
Highly questionable research recruitment techniques are also occurring in the US. On November 29, 2005, in Texas, CBS News channel 42 reporter, Nanci Wilson, revealed records showing that staff at state mental hospitals in Texas help recruit patients into studies of experimental drugs not approved by the FDA.
At a state hospital in San Antonio, CBS News found 16 beds set aside to allow drug companies to conduct studies on mental patients under the state’s care. CBS 42 asked Austin psychiatrist, Deborah Peel, to review some of the records they obtained.
Dr Peel said the situation raised serious questions as to whether this is moral and ethical treatment. “They are essentially turning the state hospital population into research subjects,” she noted.
Texas hospital officials claim the mentally ill patients give informed consent by signing a detailed form describing the risks and benefits of participating in the study. But Dr Peel says, “I think there are real questions how informed their consent would be under those situations, because these are not people who have the means to choose to go elsewhere for treatment, and so, there’s a powerful element of pressure, of coercion that they have to feel.”
“Once again,” Dr Peel points out, “we have people who have no means, who are dependent on the state system, and the state system is working hand-in-glove with private corporations.”
In many studies, CBS news investigators determined that patients had been taken off drugs that were working and in the new study, some patients were given the experimental drug while others received a placebo.
Critics point out that for patients taking a new drug, there is no guarantee it will work, and the risks and long-term effects are not known. “To take people off medication when they have just been admitted for an inability to function and might have even been a harm to themselves or others, that raises real questions for me,” Dr Peel told CBC News.
What’s worse, she says, is that patients are not told whether they are taking a placebo or a drug even when they are discharged from the hospital during the study. They could get suicidal, she said, or could harm others.
The FDA has ignored atrocities in research involving mentally ill subjects for years. Back in 1998, a review of the data on atypical antipsychotic drugs submitted to the FDA, obtained with FOIA requests by Robert Whitaker, revealed numerous safety problems for subjects who participated in the trials.
Mr Whitaker found that among 12,176 patients from the US and abroad at the time the data was submitted, there were 88 deaths, including 38 suicides, meaning there was an overall death rate of 1 out of every 138 patients, according to his article in the November 17, 1998 Boston Globe.
The suicide rate in trials was found to be 2 to five times higher than the norm. In the medical literature, Mr Whitaker reported, suicide rates for schizophrenics ranged from two to five deaths per 1,000 per year, while the rate in trials was close to 10 per 1,000.
In addition, he found that for the three approved drugs in the study – Zyprexa, Risperdal, and Seroquel – 60% of the 7,269 patients who received the drugs dropped out before the end of the study, which typically lasted six to 8 weeks.
In the 1990s the prospect of antipsychotic drugs gaining FDA approval, promised a major market for Big Pharma and therefore, drug companies needed to recruit trial subjects quickly. And drug companies were willing to pay top dollars to researchers for each patient recruited.
In the Boston Globe article, Mr Whitaker discusses a criminal case in Georgia that reveals just how far researcher are willing to go to meet recruitment goals.
Dr Richard Borison, chairman of the psychiatry department at the Medical College of Georgia, and Bruce Diamond, a pharmacologist on the school’s faculty, were favorites for schizophrenia drugs and demonstrated a knack for rounding up psychotic patients quickly for trials funded Eli Lilly, Janssen, Zeneca, and Novartis.
As faculty members, Borison and Diamond were supposed to get approval for research and payments for trials were supposed to go the school. But according to Georgia authorities, who indicted the duo in early 1997, in 1989 they started having the drug makers send payments directly to them.
They simply opened an office across from the school, hired a commercial service to do ethical reviews of their studies, and placed their staff on the school’s payroll but kept all the money for themselves.
As unbelievable as it may seem, the scheme worked for about 7 years. From 1989 to 1996, Borison and Diamond made over $10 million including more than $4 million from schizophrenia drugs, according to the indictment and testimony during an investigation by the Augusta Veterans Affairs Hospital, where Borison was chief of psychiatry.
And these guys were slick. To recruit the mostly male patients, they hired good-looking young women, who testified that they were paid bonuses that ran into the thousands, and one staffer was even given a Honda Accord.
To find their recruits, workers looked for mentally ill patients who were stable and living in the community and offered them $150 to check into the VA so they could be in a study. Patients already in locked wards were offered cigarettes to participate.
Study coordinators, many with no medical training, determined whether a patient belonged in a study. According to an FDA investigation, untrained staff drew blood samples and adjusted doses of the drugs, and Borison and Diamond hardly ever saw the patients at all.
But the two researchers lived high off the hog, according to Georgia authorities. They socked away more than $5 million in cash and securities, spent nearly a half a million on antiques and drove Mercedes-Benz vehicles.
But as the old saying goes, all good things must end. In December, 1997, Diamond pleaded guilty to theft and bribery charges and was fined, $125,000, sentenced to 5 years in prison, and ordered to pay $1.1 million to the college.
Borison pleaded guilty to theft and racketeering charges, was sentenced to 15 years in prison, fined $125,000, and ordered to pay $4.26 million to the college.
To cover all bases, over the years, Big Pharma has also become adept at corrupting the judicial process.
For instance, Dr Bruce Levine, PhD, Clinical Psychologist and author of, World Gone Crazy, tells a story about Eli Lilly corrupting the judicial process in a case that began in 1989 when Joseph Wesbecker opened fire at his former place of employment, killing 8 people and wounding 12 more, before committing suicide, a month after he began taking Prozac. The victims of the shooting sued Eli Lilly, claiming that Prozac had pushed the guy over the edge.
It has long been known that Prozac induces violence in some patients but the FDA never required Lilly to list violence on the drug’s label. But as it turns out, five of the 9 members on the 1991 FDA advisory panel investigating the association between Prozac and violence that voted against requiring a warning label for violence, had ties to Big Pharma and two of the members had served as lead investigators for Lilly-funded Prozac studies.
The Wesbecker trial did not take place until 1994, but in the meantime, according to Dr Levine, “Eli Lilly had been settling many Prozac violence cases behind closed doors.”
In fact, he says, more than 150 Prozac lawsuits had been filed by the end of 1994, so “it was looking for a showcase trial that it could win.”
A crucial component of the victims’ legal strategy in the Wesbecker case was for the jury to hear about Lilly’s history of reckless disregard toward consumers, especially about the drug Oraflex, introduced in 1982 but taken off the market 3 months later.
“A US Justice Department investigation linked Oraflex to the deaths of more than 100 patients,” Dr Levine notes, “and concluded that Lilly had misled the FDA.”
In the end, Lilly was charged with 25 counts related to mislabeling side effects and pled guilty.
At the Wesbecker trial, Lilly attorneys argued that the Oraflex information would be too prejudicial for the jury to hear and the Judge initially agreed. However, when Lilly attorneys used witnesses to testify about it’s superb system of collecting and analyzing side effects, the Judge said that Lilly had opened the door to evidence to the contrary and so the Oraflex information would also be allowed in.
However, to Judge’s amazement,” Dr Levine says, “victims’ attorneys never presented the Oraflex evidence and Eli Lilly won the case. “
It was later learned that Lilly was successful in corrupting the judicial process in the case by cutting a secret deal with victims’ attorneys to pay them and their clients not to introduce the damaging Oraflex evidence.
However, Dr Levine says, the Judge “smelled a rat” and fought for an investigation, and in 1997, Lilly quietly agreed to the verdict being changed from a victory to “dismissed as settled.”
Legal experts are finding ways to expose and punish Big Pharma for conducting fraudulent research that requires no involvement by the nation’s compromised regulatory agencies. Barry Turner, Lecturer in Law at Leeds Law School in the UK, is a great fan of the False Claims Act legislation in the US.
As an academic lawyer, he has for a number of years been involved in litigation regarding the activities of the pharmaceutical industry and for the past two years, he has been involved in Qui tam litigation preparation.
“Tying Qui tam into human rights and civil liberties issues is easy,” Mr Turner says. “When President Lincoln initiated this law in 1863 it was because Union soldiers were going into battle in shoddy boots and uniforms equipped with guns and ammunition that were third rate,” he explains. “All because ‘businessmen’ saw the war as a gravy train.”
“Qui tam,” Mr Turner explains, “protects taxpayers and since tax revenue is the lifeblood of any state, any evasion of liability or deliberate defrauding of a taxpayers is an attack on all taxpayers and consequently all citizens.”
Qui tam in its long history, he says, has brought to book many crooks who stole from the US taxpayer and is based on the individual citizen being able to blow the whistle for the benefit of fellow citizens and the country.
The more recent Sarbanes-Oxley Act of 2002 (SOX), was enacted in the wake of the Enron and WorldCom scandals, and was designed to restore investor confidence in the nation’s financial markets by improving corporate responsibility through changes in corporate governance and accounting practices and by providing whistleblower protection to employees of publicly traded companies who report fraud.
SOX contains a civil and a criminal whistleblower provision. Section 806, creates a civil cause of action for employees who have been subject to retaliation for whistleblowing, and Section 1107, makes it a felony for anyone to knowingly retaliate against or take any action harmful to any person, including interfering with employment, for providing truthful information relating to the commission or possible commission of a federal offense.
According to Mr Turner, SOX is not limited to shareholders of a company. “What needs to be understood,” he says, “is that many millions of people who own no stock at all get defrauded in scams all the time.”
“Those who pay into pension funds are vulnerable to the financial shenanigans not only of fund managers but of boards of companies,” he explains, “and CEO’s that fail to police the companies activities or in some cases actively encourage fraud and reckless business practices.”
SOX came into being to prevent those financial shenanigans, he says. “The fat cats may lose a small amount of their stake in any scam,” he points out, “but the little man as ever stands to lose all.”
One of the features of SOX, he says, is the ability to bring an action against those who recklessly and fraudulently deal with stockholders money. Big Pharma, and its handmaiden psychiatry, he notes, is built on fraud.
For example, Mr Turner explains, Ritalin fraud consists of labeling millions of children as basket cases based on fraudulent research and a consensus of the vested interest.
“SSRI fraud,” he advises, “extends depression into the world of normal human experience to ever-extend the peddling of the often useless and frequently dangerous treatments.”
In other instances, he says, many poor and elderly people are starved of life saving drugs because the budgets of Medicare and Medicaid are bled dry by claims from drug companies for ‘me too’ drugs that in many cases are superfluous.
“Even where there is some justification for the use of these drugs,” he explains, “there is a drive to constantly increase the dose above the minimum effective one because a ‘minimum effective dose’ to the drug company means minimum effective profit.”
“Where money is diverted from real healthcare provisions, to a profit greedy industry that manufactures an illness to fit the drug,” he notes, “rather than provide drugs for real illnesses, then the most fundamental of constitutional rights ‘Life, Liberty and the Pursuit of Happiness’ is most at risk.”
Every unnecessary dose of Ritalin, Prozac, Paxil, and other psychiatric drugs prescribed and paid for with US tax dollars, he says, deprives patients dependant on state healthcare programs of drugs they need for cancer, diabetes, heart disease and other serious conditions.
In addition, Mr Turner points out that, “the marketing of these drugs and the ever expanding definition of psychiatric disorder that is part of this marketing strategy labels, discriminates against, and stigmatizes hundreds of thousands of American Citizens.”
“It is indeed a dramatic irony,” he says, “that in very many of these cases the US taxpayer gets to fund an industry that acts in a manner so alien to the American Constitutional ideals.”
For purposes of the litigation, “knowingly” is defined as: (1) Actual knowledge of the false information; (2) Acts in deliberate ignorance of the truth or falsity of the information; or (3) Acts in reckless disregard of the truth or falsity of the information.
Therefore, according to Mr Turner, “inducing people to invest in companies that engage in illegal and reckless activity is a violation of SOX.”
“Inducing people to take vast amounts of drugs that are known to be harmful and deliberately hiding the known dangers is a violation of SOX,” he contends.
“One day this edifice will come tumbling down,” he says, “and what will the investors in Big Pharma say then?”
In light of the Vioxx disaster, Mr Turner says, we should perhaps ask people who invested in Merck.
“Those at the top of this company,” he notes, “gambled with the lives of patients and the money of stockholders in equal bad faith when they engaged in fraudulent and dishonest behavior that allowed a dangerous drug to be marketed.”
“Those who today peddle drugs for fictitious illnesses and push dangerous and useless medications on the children,” he warns, “in our societies are doing just this.”
Merck acted with reckless disregard for the truth because it had prior knowledge of the adverse effects of Vioxx. The same goes for Eli Lilly and its prior knowledge of the lack of efficacy of Prozac and GlaxoSmithKline’s knowledge of Paxil’s suicide ideation
While suppressing negative studies, these companies placed drugs on the market that were known to be faulty in one way or another. All of these drugs have cost taxpayers dearly, not to mention the personal suffering they have inflicted in other ways
In considering other acts of fraud, Mr Turner looked at the Pharma backed charities that are based on fraudulent research to see what Federal laws they may be violating.
“Since a number of imaginative illnesses are based on this fabricated research and since a number of charities are based on the ‘imaginative illnesses’ that arose out of the imaginative research,” he says, “its just a matter of connecting the dots.”
Because charities receive tax breaks, he says, fraudulent charities defraud US taxpayers.
“The fraud in this industry is not divided into that which injures by over drugging and that which cheats taxpayers and stockholders out of their money,” he explains. “They are two sides of the same counterfeit coin.”
Mr Turner says we must tackle them together, and that lawyers in the US should be actively seeking clients who have lost money by these frauds and getting the matter before the Security and Exchange Commission now.