Attorney Michael Connett summarizes 10 basic facts about fluoride that should be considered in any discussion about whether to fluoridate water. To download the flyer that accompanies this video, visit: http://www.fluoridealert.org/uploads/…. To watch Michael debate two advocates of fluoridation, see: http://www.wpsu.org/conversationslive….
The manufacturer of a blood-thinning drug tried to hide results of an internal study that the manufacturer feared would hurt sales of the widely-advertised medication, according to recently-unsealed court documents.
Boehringer Ingelheim, manufacturer of Pradaxa, is being sued by patients and their families, charging it failed to properly warn users about possible dangers of the drug. More than 1,000 of those using Pradaxa have died from bleeding, Katie Thomas of The New York Times reported.
Some of the papers released by Chief Judge David R. Herndon of the United States District Court in East St. Louis, Ill., indicated that a research paper would contradict the company’s claims that regular blood monitoring is not necessary while taking Pradaxa. The lack of regular monitoring is one of the main selling points of the drug over warfarin, a drug long used in the prevention of blood clots and strokes. Warfarin requires frequent blood monitoring and attention to diet.
Boehringer Ingelheim emails released by the court show concern about the effect a change in recommended monitoring would have on sales of Pradaxa. “This may not be a onetime test and could result in a more complex message (regular monitoring), and a weaker value proposition … vs. competitors,” one employee wrote.
An email from another employee expressed concern about the drug’s safety risks in older patients, and said “there may be a role” for one or two blood tests in Pradaxa patients.
The case highlights the fact that much of the research on drugs is performed by the drug makers themselves, who have a financial interest in ensuring their products are approved by regulators.
The research paper, written by Paul A. Reilly, a clinical program director at Boehringer Ingelheim, found that some patients absorb too little of the drug to prevent strokes. It also said another group absorbs so much that they are at a higher risk for bleeding. These issues could be addressed with blood monitoring to ensure that patients have the proper levels of the drug in their bloodstream. Draft versions of the paper gave optimal levels of Pradaxa in a patient’s bloodstream.
Reilly’s paper was published in the February 2014 issue of the Journal of the American College of Cardiology, but some of the conclusions about blood monitoring that appeared in the draft version aren’t in the final report.
In a statement, Boehringer Ingelheim said the unsealed documents “represent small fragments of the robust discussion and debate that is a vital component in all scientific inquiry, and in the research and development of any important medication such as Pradaxa.”
One company supervisor, Dr. Jutta Heinrich-Nols, warned that publishing Reilly’s paper could make it “extremely difficult” for the company to defend its claims that Pradaxa did not require regular blood monitoring, the Times said.
In addition, there is so far no antidote to Pradaxa’s effects. With warfarin, physicians can administer doses of Vitamin K to counteract that drug’s effects in case a patient starts hemorrhaging.
The Justice Department has previously cited the company for intentionally making “unsubstantiated claims about the efficacy” of their drug Aggrenox, which is intended to prevent subsequent strokes, or strokes due to blood clots.
The Pradaxa documents were released the same week that Physicians for Integrity in Medical Research sued the Food and Drug Administration over the heart medication roflumilast, claiming it should be pulled off the market. The drug, made by Forest Laboratories and intended to treat chronic obstructive pulmonary disease (COPD), does more harm than good, according to the plaintiff.
To Learn More:
Study of Drug for Blood Clots Caused a Stir, Records Show (by Katie Thomas, New York Times)
New Emails in Pradaxa Case Show Concern Over Profit (by Katie Thomas, New York Times)
A Promising Drug With a Flaw (by Katie Thomas, New York Times)
Pradaxa Manufacturer Has History of Illegal Activities, Ties To Controversial Groups (by Alisha Mims, Ring of Fire)
Doctors Group Sues FDA to Withdraw Approval of Heart Drug (by Noel Brinkerhoff, AllGov)
By Andrew M. Weiss | Skeptical Inquiry | May 6, 2009
In 1950, approximately 7,500 children in the United States were diagnosed with mental disorders. That number is at least eight million today, and most receive some form of medication.
Is this progress or child abuse?
In the winter of 2000, the Journal of the American Medical Association published the results of a study indicating that 200,000 two-to four-year-olds had been prescribed Ritalin for an “attention disorder” from 1991 to 1995. Judging by the response, the image of hundreds of thousands of mothers grinding up stimulants to put into the sippy cups of their preschoolers was apparently not a pretty one. Most national magazines and newspapers covered the story; some even expressed dismay or outrage at this exacerbation of what already seemed like a juggernaut of hyper-medicalizing childhood. The public reaction, however, was tame; the medical community, after a moment’s pause, continued unfazed. Today, the total toddler count is well past one million, and influential psychiatrists have insisted that mental health prescriptions are appropriate for children as young as twelve months. For the pharmaceutical companies, this is progress.
In 1995, 2,357,833 children were diagnosed with ADHD (Woodwell 1997)—twice the number diagnosed in 1990. By 1999, 3.4 percent of all American children had received a stimulant prescription for an attention disorder. Today, that number is closer to ten percent. Stimulants aren’t the only drugs being given out like candy to our children. A variety of other psychotropics like antidepressants, antipsychotics, and sedatives are finding their way into babies’ medicine cabinets in large numbers. In fact, the worldwide market for these drugs is growing at a rate of ten percent a year, $20.7 billion in sales of antipsychotics alone (for 2007, IMSHealth 2008).
While the sheer volume of psychotropics being prescribed for children might, in and of itself, produce alarm, there has not been a substantial backlash against drug use in large part because of the widespread perception that “medically authorized” drugs must be safe. Yet, there is considerable evidence that psychoactive drugs do not take second place to other controlled pharmaceuticals in carrying grave and substantial risks. All classes of psychoactive drugs are associated with patient deaths, and each produces serious side effects, some of which are life-threatening.
In 2005, researchers analyzed data from 250,000 patients in the Netherlands and concluded that “we can be reasonably sure that antipsychotics are associated in something like a threefold increase in sudden cardiac death, and perhaps that older antipsychotics may be worse” (Straus et al. 2004). In 2007, the FDA chose to beef up its black box warning (reserved for substances that represent the most serious danger to the public) against antidepressants concluding, “the trend across age groups toward an association between antidepressants and suicidality . . . was convincing, particularly when superimposed on earlier analyses of data on adolescents from randomized, controlled trials” (Friedman and Leon 2007). Antidepressants have been banned for use with children in the UK since 2003. According to a confidential FDA report, prolonged administration of amphetamines (the standard treatment for ADD and ADHD) “may lead to drug dependence and must be avoided.” They further reported that “misuse of amphetamine may cause sudden death and serious cardiovascular adverse events” (Food and Drug Administration 2005). The risk of fatal toxicity from lithium carbonate, a not uncommon treatment for bipolar disorder, has been well documented since the 1950s. Incidents of fatal seizures from sedative-hypnotics, especially when mixed with alcohol, have been recorded since the 1920s.
Psychotropics carry nonfatal risks as well. Physical dependence and severe withdrawal symptoms are associated with virtually all psychoactive drugs. Psychological addiction is axiomatic. Concomitant side effects range from unpleasant to devastating, including: insulin resistance, narcolepsy, tardive dyskenisia (a movement disorder affecting 15–20 percent of antipsychotic patients where there are uncontrolled facial movements and sometimes jerking or twisting movements of other body parts), agranulocytosis (a reduction in white blood cells, which is life threatening), accelerated appetite, vomiting, allergic reactions, uncontrolled blinking, slurred speech, diabetes, balance irregularities, irregular heartbeat, chest pain, sleep disorders, fever, and severe headaches. The attempt to control these side effects has resulted in many children taking as many as eight additional drugs every day, but in many cases, this has only compounded the problem. Each “helper” drug produces unwanted side effects of its own.
The child drug market has also spawned a vigorous black market in high schools and colleges, particularly for stimulants. Students have learned to fake the symptoms of ADD in order to obtain amphetamine prescriptions that are subsequently sold to fellow students. Such “shopping” for prescription drugs has even spawned a new verb. The practice is commonly called “pharming.” A 2005 report from the Partnership for a Drug Free America, based on a survey of more than 7,300 teenagers, found one in ten teenagers, or 2.3 million young people, had tried prescription stimulants without a doctor’s order, and 29 percent of those surveyed said they had close friends who have abused prescription stimulants.
In a larger sense, the whole undertaking has had the disturbing effect of making drug use an accepted part of childhood. Few cultures anywhere on earth and anytime in the past have been so willing to provide stimulants and sedative-hypnotics to their offspring, especially at such tender ages. An entire generation of young people has been brought up to believe that drug-seeking behavior is both rational and respectable and that most psychological problems have a pharmacological solution. With the ubiquity of psychotropics, children now have the means, opportunity, example, and encouragement to develop a lifelong habit of self-medicating.
Common population estimates include at least eight million children, ages two to eighteen, receiving prescriptions for ADD, ADHD, bipolar disorder, autism, simple depression, schizophrenia, and the dozens of other disorders now included in psychiatric classification manuals. Yet sixty years ago, it was virtually impossible for a child to be considered mentally ill. The first diagnostic manual published by American psychiatrists in 1952, DSM-I, included among its 106 diagnoses only one for a child: Adjustment Reaction of Childhood/Adolescence. The other 105 diagnoses were specifically for adults. The number of children actually diagnosed with a mental disorder in the early 1950s would hardly move today’s needle. There were, at most, 7,500 children in various settings who were believed to be mentally ill at that time, and most of these had explicit neurological symptoms.
Of course, if there really are one thousand times as many kids with authentic mental disorders now as there were fifty years ago, then the explosion in drug prescriptions in the years since only indicates an appropriate medical response to a newly recognized pandemic, but there are other possible explanations for this meteoric rise. The last fifty years has seen significant social changes, many with a profound effect on children. Burgeoning birth rates, the decline of the extended family, widespread divorce, changing sexual and social mores, households with two working parents—it is fair to say that the whole fabric of life took on new dimensions in the last half century. The legal drug culture, too, became an omnipresent adjunct to daily existence. Stimulants, analgesics, sedatives, decongestants, penicillins, statins, diuretics, antibiotics, and a host of others soon found their way into every bathroom cabinet, while children became frequent visitors to the family physician for drugs and vaccines that we now believe are vital to our health and happiness. There is also the looming motive of money. The New York Times reported in 2005 that physicians who had received substantial payments from pharmaceutical companies were five times more likely to prescribe a drug regimen to a child than those who had refused such payments.
So other factors may well have contributed to the upsurge in psychiatric diagnoses over the past fifty years. But even if the increase reflects an authentic epidemic of mental health problems in our children, it is not certain that medication has ever been the right way to handle it. The medical “disease” model is one approach to understanding these behaviors, but there are others, including a hastily discarded psychodynamic model that had a good record of effective symptom relief. Alternative, less invasive treatments, too, like nutritional treatments, early intervention, and teacher and parent training programs were found to be at least as effective as medication in long-term reduction of a variety of symptoms (of ADHD, The MTA Cooperative Group 1999).
Nevertheless, the medical-pharmaceutical alliance has largely shrugged off other approaches and scoffed at the potential for conflicts of interest and continues to medicate children in ever-increasing numbers. With the proportion of diagnosed kids growing every month, it may be time to take another look at the practice and soberly reflect on whether we want to continue down this path. In that spirit, it is not unreasonable to ask whether this exponential expansion in medicating children has another explanation altogether. What if children are the same as they always were? After all, virtually every symptom now thought of as diagnostic was once an aspect of temperament or character. We may not have liked it when a child was sluggish, hyperactive, moody, fragile, or pestering, but we didn’t ask his parents to medicate him with powerful chemicals either. What if there is no such thing as mental illness in children (except the small, chronic, often neurological minority we once recognized)? What if it is only our perception of childhood that has changed? To answer this, we must look at our history and at our nature.
The human inclination to use psychoactive substances predates civilization. Alcohol has been found in late Stone Age jugs; beer may have been fermented before the invention of bread. Nicotine metabolites have been found in ancient human remains and in pipes in the Near East and Africa. Knowledge of Hul Gil, the “joy plant,” was passed from the Sumerians, in the fifth millennium b.c.e., to the Assyrians, then in serial order to the Babylonians, Egyptians, Greeks, Persians, Indians, then to the Portuguese who would introduce it to the Chinese, who grew it and traded it back to the Europeans. Hul Gil was the Sumerian name for the opium poppy. Before the Middle Ages, economies were established around opium, and wars were fought to protect avenues of supply.
With the modern science of chemistry in the nineteenth century, new synthetic substances were developed that shared many of the same desirable qualities as the more traditional sedatives and stimulants. The first modern drugs were barbiturates—a class of 2,500 sedative/hypnotics that were first synthesized in 1864. Barbiturates became very popular in the U.S. for depression and insomnia, especially after the temperance movement resulted in draconian anti-drug legislation (most notoriously Prohibition) just after World War I. But variety was limited and fears of death by convulsion and the Winthrop drug-scare kept barbiturates from more general distribution.
Stimulants, typically caffeine and nicotine, were already ubiquitous in the first half of the twentieth century, but more potent varieties would have to wait until amphetamines came into widespread use in the 1930s. Amphetamines were not widely known until the 1920s and 1930s when they were first used to treat asthma, hay fever, and the common cold. In 1932, the Benzedrine Inhaler was introduced to the market and was a huge over-the-counter success. With the introduction of Dexedrine in the form of small, cheap pills, amphetamines were prescribed for depression, Parkinson’s disease, epilepsy, motion sickness, night-blindness, obesity, narcolepsy, impotence, apathy, and, of course, hyperactivity in children.
Amphetamines came into still wider use during World War II, when they were given out freely to GIs for fatigue. When the GIs returned home, they brought their appetite for stimulants to their family physicians. By 1962, Americans were ingesting the equivalent of forty-three ten-milligram doses of amphetamine per person annually (according to FDA manufacturer surveys).
Still, in the 1950s, the family physician’s involvement in furnishing psychoactive medications for the treatment of primarily psychological complaints was largely sub rosa. It became far more widespread and notorious in the 1960s. There were two reasons for this. First, a new, safer class of sedative hypnotics, the benzodiazepines, including Librium and Valium, were an instant sensation, especially among housewives who called them “mothers’ helpers.” Second, amphetamines had finally been approved for use with children (their use up to that point had been “off-label,” meaning that they were prescribed despite the lack of FDA authorization).
Pharmaceutical companies, coincidentally, became more aggressive in marketing their products with the tremendous success of amphetamines. Valium was marketed directly to physicians and indirectly through a public relations campaign that implied that benzodiazepines offered sedative/hypnotic benefits without the risk of addiction or death from drug interactions or suicide. Within fifteen years of its introduction, 2.3 billion Valium pills were being sold annually in the U.S. (Sample 2005).
So, family physicians became society’s instruments: the suppliers of choice for legal mood-altering drugs. But medical practitioners required scientific authority to protect their reputations, and the public required a justification for its drug- seeking behavior. The pharmaceutical companies were quick to offer a pseudoscientific conjecture that satisfied both. They argued that neurochemical transmitters, only recently identified, were in fact the long sought after mediators of mood and activity. Psychological complaints, consequently, were a function of an imbalance of these neural chemicals that could be corrected with stimulants and sedatives (and later antidepressants and antipsychotics). While the assertion was pure fantasy without a shred of evidence, so little was known about the brain’s true actions that the artifice was tamely accepted. This would later prove devastating when children became the targets of pharmaceutical expansion.
With Ritalin’s FDA approval for the treatment of hyperactivity in children, the same marketing techniques that had been so successful with other drugs were applied to the new amphetamine. Pharmaceutical companies had a vested interest in the increase in sales; they spared no expense in convincing physicians to prescribe them. Cash payments, stock options, paid junkets, no-work consultancies, and other inducements encouraged physicians to relax their natural caution about medicating children. Parents also were targeted. For example, CIBA, the maker of Ritalin, made large direct payments to parents’ support groups like CHADD (Children and Adults with Attention Deficit/Hyperactivity Disorder) (The Merrow Report 1995). To increase the acceptance of stimulants, drug companies paid researchers to publish favorable articles on the effectiveness of stimulant treatments. They also endowed chairs and paid for the establishment of clinics in influential medical schools, particularly ones associated with universities of international reputation. By the mid 1970s, more than half a million children had already been medicated primarily for hyperactivity.
The brand of psychiatry that became increasingly popular in the 1980s and 1990s did not have its roots in notions of normal behavior or personality theory; it grew out of the concrete, atheoretical treatment style used in clinics and institutions for the profoundly disturbed. German psychiatrist Emil Kraepelin, not Freud, was the God of mental hospitals, and pharmaceuticals were the panacea. So the whole underlying notion of psychiatric treatment, diagnosis, and disease changed. Psychiatry, which had straddled psychology and medicine for a hundred years, abruptly abandoned psychology for a comfortable sinecure within its traditional parent discipline. The change was profound.
People seeking treatment were no longer clients, they were patients. Their complaints were no longer suggestive of a complex mental organization, they were symptoms of a disease. Patients were not active participants in a collaborative treatment, they were passive recipients of symptom-reducing substances. Mental disturbances were no longer caused by unique combinations of personality, character, disposition, and upbringing, they were attributed to pre-birth anomalies that caused vague chemical imbalances. Cures were no longer anticipated or sought; mental disorders were inherited illnesses, like birth defects, that could not be cured except by some future magic, genetic bullet. All that could be done was to treat symptoms chemically, and this was being done with astonishing ease and regularity.
In many ways, children are the ideal patients for drugs. By nature, they are often passive and compliant when told by a parent to take a pill. Children are also generally optimistic and less likely to balk at treatment than adults. Even if they are inclined to complain, the parent is a ready intermediary between the physician and the patient. Parents are willing to participate in the enforcement of treatments once they have justified them in their own minds and, unlike adults, many kids do not have the luxury of discontinuing an unpleasant medication. Children are additionally not aware of how they ought to feel. They adjust to the drugs’ effects as if they are natural and are more tolerant of side effects than adults. Pharmaceutical companies recognized these assets and soon were targeting new drugs specifically at children.
But third-party insurance providers balked at the surge in costs for treatment of previously unknown, psychological syndromes, especially since unwanted drug effects were making some cases complicated and expensive. Medicine’s growing prosperity as the purveyor of treatments for mental disorders was threatened, and the industry’s response was predictable. Psychiatry found that it could meet insurance company requirements by simplifying diagnoses, reducing identification to the mere appearance of certain symptoms. By 1980, they had published all new standards.
Lost in the process was the fact that the redefined diagnoses (and a host of new additions) failed to meet minimal standards of falsifiability and differentiability. This meant that the diagnoses could never be disproved and that they could not be indisputably distinguished from one another. The new disorders were also defined as lists of symptoms from which a physician could check off a certain number of hits like a Chinese menu, which led to reification, an egregious scientific impropriety. Insurers, however, with their exceptions undermined and under pressure from parents and physicians, eventually withdrew their objections. From that moment on, the treatment of children with powerful psychotropic medications grew unchecked.
As new psychotropics became available, their uses were quickly extended to children despite, in many cases, indications that the drugs were intended for use with adults only. New antipsychotics, the atypicals, were synthesized and marketed beginning in the 1970s. Subsequently, a new class of antidepressants like Prozac and Zoloft was introduced. These drugs were added to the catalogue of childhood drug treatments with an astonishing casualness even as stimulant treatment for hyperactivity continued to burgeon.
In 1980, hyperactivity, which had been imprudently named “minimal brain dysfunction” in the 1960s, was renamed Attention Deficit Disorder in order to be more politic, but there was an unintended consequence of the move. Parents and teachers, familiar with the name but not always with the symptoms, frequently misidentified children who were shy, slow, or sad (introverted rather than inattentive) as suffering from ADD. Rather than correct the mistake, though, some enterprising physicians responded by prescribing the same drug for the opposite symptoms. This was justified on the grounds that stimulants, which were being offered because they slowed down hyperactive children, might very well have the predicted effect of speeding up under -active kids. In this way, a whole new population of children became eligible for medication. Later, the authors of DSM-III memorialized this practice by renaming ADD again, this time as ADHD, and redefining ADD as inattention. Psychiatry had reached a new level: they were now willing to invent an illness to justify a treatment. It would not be the last time this was done.
In the last twenty years, a new, more disturbing trend has become popular: the re-branding of legacy forms of mental disturbance as broad categories of childhood illness. Manic depressive illness and infantile autism, two previously rare disorders, were redefined through this process as “spectrum” illnesses with loosened criteria and symptom lists that cover a wide range of previously normal behavior. With this slim justification in place, more than a million children have been treated with psychotropics for bipolar disorder and another 200,000 for autism. A recent article in this magazine “The Bipolar Bamboozle” (Flora and Bobby 2008) illuminates how and why an illness that once occurred twice in every 100,000 Americans, has been recast as an epidemic affecting millions.
To overwhelmed parents, drugs solve a whole host of ancillary problems. The relatively low cost (at least in out-of-pocket dollars) and the small commitment of time for drug treatments make them attractive to parents who are already stretched thin by work and home life. Those whose confidence is shaken by indications that their children are “out of control” or “unruly” or “disturbed” are soothed by the seeming inevitability of an inherited disease that is shared by so many others. Rather than blaming themselves for being poor home managers, guardians with insufficient skills, or neglectful caretakers, parents can find comfort in the thought that their child, through no fault of theirs, has succumbed to a modern and widely accepted scourge. A psychiatric diagnosis also works well as an authoritative response to demands made by teachers and school administrators to address their child’s “problems.”
Once a medical illness has been identified, all unwanted behavior becomes fruit of the same tree. Even the children themselves are often at first relieved that their asocial or antisocial impulses reflect an underlying disease and not some flaw in their characters or personalities.
In the last analysis, childhood has been thoroughly and effectively redefined. Character and temperament have been largely removed from the vocabulary of human personality. Virtually every single undesirable impulse of children has taken on pathological proportions and diagnostic significance. Yet, if the psychiatric community is wrong in their theories and hypotheses, then a generation of parents has been deluded while millions of children have been sentenced to a lifetime of ingesting powerful and dangerous drugs.
Considering the enormous benefits reaped by the medical community, it is no surprise that critics have argued that the whole enterprise is a cynical, reckless artifice crafted to unfairly enrich them. Even though this is undoubtedly not true, physicians and pharmaceutical companies must answer for the rush to medicate our most vulnerable citizens based on little evidence, a weak theoretical model, and an antiquated and repudiated philosophy. For its part, the scientific community must answer for its timidity in challenging treatments made in the absence of clinical observation and justified by research of insufficient rigor performed by professionals and institutions whose objectivity is clearly in question, because their own interests are materially entwined in their findings.
It should hardly be necessary to remind physicians that even if their diagnoses are real, they are still admonished by Galen’s dictum Primum non nocere, or “first, do no harm.” If with no other population, this ought to be our standard when dealing with children. Yet we have chosen the most invasive, destructive, and potentially lethal treatment imaginable while rejecting other options that show great promise of being at least as effective and far safer. But these other methods are more expensive, more complicated, and more time-consuming, and thus far, we have not proved willing to bear the cost. Instead, we have jumped at a discounted treatment, a soft-drink- machine cure: easy, cheap, fast, and putatively scientific. Sadly, the difference in price is now being paid by eight million children.
Mental illness is a fact of life, and it is naïve to imagine that there are not seriously disturbed children in every neighborhood and school. What is more, in the straitened economy of child rearing and education, medication may be the most efficient and cost effective treatment for some of these children. Nevertheless, to medicate not just the neediest, most complicated cases but one child in every ten, despite the availability of less destructive treatments and regardless of doubtful science, is a tragedy of epic proportions.
What we all have to fear, at long last, is not having been wrong but having done wrong. That will be judged in a court of a different sort. Instead of humility, we continue to feed drugs to our children with blithe indifference. Even when a child’s mind is truly disturbed (and our standards need to be revised drastically on this score), a treatment model that intends to chemically palliate and manage ought to be our last resort, not our first option. How many more children need to be sacrificed for us to see the harm in expediency, greed, and plain ignorance?
Andrew Weiss holds a PhD in school-clinical psychology from Hofstra University. He served on the faculty of Iona College and has been a senior school administrator in Chappaqua, New York. He has published a number of articles on technology in education. E-mail: anweiss [at] optonline.net.
A new report describing the bizarre and dangerous side effects of the sleep aid Ambien has once again raised questions about one of the United States’ most popular prescription drugs.
In a story by the Fix, Allison McCabe chronicled the numerous cases in which Ambien has caused individuals to commit unsafe, and sometimes deadly acts.
In 2009, 45-year-old Robert Stewart was convicted on eight charges of second-degree murder after he killed eight people in a nursing home. He was originally charged with first-degree murder, but by claiming his tirade was Ambien-induced he was able to have the charges lessened and sentenced to 142-179 years in prison.
In a similar case, Thomas Chester Page of South Carolina was sentenced on five counts of attempted murder despite his claims that Ambien was the cause of a shootout with officers. He received 30 years of prison on each count, to be served concurrently.
Although the Food and Drug Administration approved Ambien in 1992, its warning labels have changed significantly over the last two decades as evidence mounted documenting the drug’s ability to induce dangerous behavior.
“After taking AMBIEN, you may get up out of bed while not being fully awake and do an activity that you do not know you are doing,” the label currently reads. “The next morning, you may not remember that you did anything during the night… Reported activities include: driving a car (“sleep-driving”), making and eating food, talking on the phone, having sex, sleep-walking.”
In the courtroom, cases related to Ambien use have ranged from shootings to child molestation charges to car accidents. In one such case, flight attendant Julie Ann Bronson from Texas ran over three people – including an 18-month old who suffered from brain damage as a result. When Bronson woke up in jail the next morning, she could barely comprehend what she had done.
“It was surreal. It was like a bad dream,” she said in May 2012. “I did the crime but I never intended to do it. I wouldn’t hurt a flea. And if I would have hit somebody, I would have stopped and helped. We’re trained in CPR.” Bronson pleaded guilty to the felony charges, but also received lesser charges by citing Ambien as the reason for her actions.
While some drug companies work on sleep aids that do not induce the kind of unpredictable and risky behavior Ambien does, the popularity of the medication raises concern over America’s prescription drug culture. The market for sleeping pills is a billion-dollar industry, yet dangerous side effects continue to be reported.
Last year, a report by the Department of Health and Human Services highlighted about 2,200 doctors for suspicious activities such as over-prescribing drugs. More than 700 Medicare doctors were also flagged for issuing what could be seen as “extreme” and potentially harmful prescriptions.
Although the report noted that some prescriptions could have been effective, it added, “prescribing high amounts on any of these measures may indicate that a physician is prescribing drugs which are not medically necessary or that he or she has an inappropriate incentive, such as a kickback, to order certain drugs.”
Soon after that report was issued, the Centers for Disease Control and Prevention found that roughly 18 women a day are dying in the United States due to prescription drug overdose, namely from painkillers like Vicodin and Oxycontin. With women making up 40 percent of all overdose deaths in 2010, these numbers marked a 400 percent increase compared to data from 1999.
The benefits of medication have also been placed under heavy scrutiny when it comes to other health issues, such as attention deficit hyperactivity disorder (ADHD). In December 2013, RT reported that the authors of the primary study promoting medication over behavioral therapy in order to treat ADHD now have serious concerns over their original results.
“I hope it didn’t do irreparable damage,” said one of the stud’s co-authors, Dr. Lilly Hechtman of Montreal’s McGill University. “The people who pay the price in the end is the kids. That’s the biggest tragedy in all of this.”
This month’s FDA guidance for reducing livestock antibiotics will actually make things worse, animal welfare and food activist groups are saying. “The FDA is using a garden hose on a forest fire,” says Farm Sanctuary Senior Policy Director Bruce Friedrich. The guidance is a “diversion” that pretends to address the problem of factory farm-driven antibiotic resistance while accomplishing nothing. Antibiotic resistant infections, widely seen as driven by factory farming, sicken 2 million a year in the US and kill 23,000, says the CDC. By asking drug makers to voluntarily renounce the use of antibiotics for livestock growth on their labels, the guidance “won’t cost the industry a penny” or reduce antibiotic use at all, says Friedrich. The reason? Factory farm antibiotics are also used to treat sickness which the crowded conditions tempt — a use that is still allowed under the guidance. Only the wording will change, says Friedrich.
In a December 11 conference call, the FDA’s Michael (“Monsanto”) Taylor, deputy commissioner for foods and veterinary medicine, William T. Flynn, deputy director for science policy and USDA’s Thomas J. Myers, associate deputy administrator, told reporters that the government is asking drug makers to voluntarily restrict the uses on their antibiotic labels –yes, asking – in a shocking gift of self-regulation. Similar honor systems exist at slaughterhouses since Hazard Analysis and Critical Control Points (HACCP) was instituted in 1998 in which industry creates its own safety plan which the government simply cosigns. A similar honor system called the Hazard Analysis and Critical Control Point-Based Inspection Models Project (HIMP) is imminent for poultry slaughterhouses.
Why are the FDA and USDA allowing industry to write its own ticket? (And why would industry write itself out of its own profits?) Because to mandate the changes would require “hundreds of separate regulations” and actions, whined government officials on the conference call. It is easier to just say please to industry.
To many reporters on the conference call, the plans sounded like fluff. If the changes are voluntary, “what will enforce” them and serve as an “incentive” asked an ABC reporter? Food producers and drug companies need no incentive retorted Michael Taylor because they are starting to phase out antibiotics “for their own reasons” — citing McDonald’s and KFC. Right.
If factory farmers actually phased out antibiotics (which prevent animals from becoming sick in high density-farming) won’t livestock producers “have to move to different buildings” asked a reporter from Reuters. That’s why we are giving industry three years to comply replied William Flynn.
Will you release the identifies of drug companies who do not comply asked another reporter? No, replied Flynn. We will give an “overview” of the level of “engagement” of industry but not individual company names. (USDA has also protected the identities of US ranches that released mad cows into the US food supply and restaurants who served them according to newspaper and government sources.)
Animal welfare groups like Farm Sanctuary, American Society for the Prevention of Cruelty to Animals and the Animal Legal Defense Fund are not the only ones calling the FDA guidance toothless and a serious capitulation to industry. Congresswoman Louise M. Slaughter, the only microbiologist in Congress, called the guidance “an inadequate response to the growing antibiotic resistant crisis caused by overuse of antibiotics on the farm.” Industry has spent over $17 million to block a bill Rep. Slaughter developed, in conjunction with the late Sen. Ted Kennedy, called the Preservation of Antibiotics for Medical Treatment Act (PAMTA), says a press release from her office.
This is not the first time government has caved to drug makers over the regulation of livestock antibiotics. In 2008, the FDA had announced that there was “evidence that extralabel use of these drugs [cephalosporins] in food-producing animals will likely cause an adverse event in humans and, as such, presents a risk to the public health,” and called for their prohibition. Notice the FDA says “will likely cause” not “could likely cause” and “presents a risk” not “could present a risk”?
But by the time hearings were held two months later and lobbyists had worked their magic, the “Cephalosporin Order of Prohibition” had somehow become a “Hearing to Review the Advances In Animal Health Within The Livestock Industry.” Prohibition — advances, same idea, right?
At the hearings, the American Veterinary Medical Association (AVMA), the Animal Health Institute, a Big Pharma trade group and the egg, chicken, turkey, milk, pork and cattle industries whined that they could not “farm” without antibiotics because more feed would be required and the animals would get sick from being immobilized over their own manure.
Afterwards, W. Ron DeHaven, DVM, who was the USDA’s top vet before leaving for industry and helming the AVMA, penned a rambling, almost incoherent 18-page letter with 62 footnotes to the FDA. Cephalosporin resistant “human pathogens” aren’t increasing, says the letter, and even if they are, they’re not affecting human health, and even they’re affecting human health, how do you know it’s from the livestock drugs, and even if it’s from the livestock drugs, the FDA has no legal authority to ban cephalosporin. Got that?
Alternately maudlin and accusatory, the letter plays on terrorism fears by calling a cephalosporin ban a “food security issue” affecting “the number of animals available for the food supply.” It also plays on humanitarian sentiments by claiming a ban would impede veterinarians’ ability “to relieve the pain and suffering of animals” as if cephalosporins are pain killers and other drugs aren’t available. (And as if antibiotics are given for animals’ welfare instead of revenue welfare!) But less than a month after the letter was sent, on November 25 the FDA quietly revoked the prohibition. Good hire, AVMA!
It is no surprise that factory farm operators fight to keep their antibiotics says Farm Sanctuary’s Bruce Friedrich. Without them, in their profit-driven “filth chambers,” the animals would simply die.
With the help of physicians, pharmaceutical makers have made billions of dollars peddling medicines to treat attention deficit disorder, leading some experts, and even one pharmaceutical executive, to declare that the marketing push has gone too far.
Last year, sales of stimulant medication intended to treat attention deficit hyperactivity disorder (ADHD) reached $9 billion—a fivefold increase from a decade ago.
Today, 15% of high school students have been diagnosed with ADHD, with about 3.5 million of them on some sort of drug marketed to treat the disorder.
Dr. Keith Conners, who has spent decades trying to help children with ADHD, has questioned the increasing rates of diagnosis, calling them “a national disaster of dangerous proportions.”
“The numbers make it look like an epidemic. Well, it’s not. It’s preposterous,” Conners, a psychologist and professor emeritus at Duke University, told The New York Times. “This is a concoction to justify the giving out of medication at unprecedented and unjustifiable levels.”
The drug industry has worked for two decades to publicize ADHD and promote its remedies to doctors, educators and parents. As a result, the disorder is now the second most frequent long-term diagnosis made in children, just behind asthma.
Drugs such as Ritalin, Adderall, Concerta, Focalin, Vyvanse, Intuniv and Strattera have been promoted to help children, but along the way, the Food and Drug Administration has cited every major ADHD drug for false and misleading advertising since 2000.
Doctors also have been criticized for taking money from drug companies to publish research and deliver presentations that encourage colleagues to prescribe these drugs, which possess significant side effects and are regulated in the same class as morphine and oxycodone because of their potential for abuse and addiction.
Now, companies want to market the medications to adults to further expand revenue-making opportunities.
Roger Griggs, the pharmaceutical executive who introduced Adderall in 1994, objects to marketing stimulants to the general public because of the risks involved. He called the drugs “nuclear bombs” that should rarely be prescribed and carefully monitored by a treating physician, according to the Times.
To Learn More:
The Selling of Attention Deficit Disorder (by Alan Schwarz, New York Times)
Latest Condition Invented by Drug Companies…Low Testosterone (by Matt Bewig, AllGov)
Drug Companies Increase Profits by Creating Fear of Diseases (and Even Diseases) (by David Wallechinsky, AllGov)
The Food and Drug Administration announced on Thursday that it would require the food industry to phase out the use of artificial trans fats in its products.
The FDA said it has made a preliminary determination that the primary source of trans fat – partially hydrogenated oils – is no longer “generally recognized as safe,” and that it plans to ban their use in the market. Some trans fat is naturally generated in meat and dairy products, and the ban will only apply to trans fat added to foods.
According to FDA Commissioner Margaret Hamburg, the decision could potentially prevent 20,000 heart attacks a year and 7,000 deaths.
Over the last decade, American consumption of trans fat has declined significantly. In 2006, the average citizen was consuming 4.6 grams of trans fat a day, while the number decreased to roughly one gram a day in 2012. Still, Hamburg said they “remain an area of significant public health concern,” according to NBC News.
Many companies began eliminating the use of trans fat when the FDA required them to list the ingredient on nutritional labels in 2006, but it can still be found in common products like frozen pizza, microwave popcorn, margarine, coffee creamer, and various desserts.
“The artery is still half clogged,” Dr. Thomas Frieden, the director of the Centers for Disease Control and Prevention, said to the New York Times. “This is about preventing people from being exposed to a harmful chemical that most of the time they didn’t even know was there.”
“It’s quite important,” he added, referring to the FDA’s new proposal. “It’s going to save a huge amount in health care costs and will mean fewer heart attacks.”
Numerous studies have shown that there is virtually no health benefit to consuming trans fat. It lowers the level of “good” cholesterol and raises levels of “bad” cholesterol, clogging the arteries and increasing the risk of heart attacks.
The FDA did not lay out a timetable for the ban. It will open its proposal to public comment for 60 days while it formulates a schedule that gives food manufacturers enough time to cooperate with the new rule.
“We want to do it in a way that doesn’t unduly disrupt markets,” Michael Taylor, the FDA’s deputy commissioner for foods, said to the Associated Press. At the same time, he said the food “industry has demonstrated that it is by and large feasible to do.”
Public health groups have welcomed the FDA’s proposal, which the agency has been collecting data for since 2009.
Should the FDA move forward with its plan, the United States will join other nations such as Denmark, Iceland, and Switzerland, in banning the ingredient.
Still, there are numerous other ingredients that have been outlawed in various countries while still being sold in the U.S. An, article by BuzzFeed over the summer noted that brominated vegetable oil, which has been linked to birth defects and organ damage, continues to be used in sports drinks and the popular soda Mountain Dew. It’s been banned in more than 100 countries.
Meanwhile, synthetic hormones rGBH and rBST, linked to cancer and infertility, continue to be given to cows and show up in dairy products that aren’t labeled otherwise. They’ve been banned in Japan, Canada, New Zealand, Australia, and the European Union.
Earlier this month, the FDA banned three out of the four brands of arsenic-laced animal feed that was being given to chickens, turkeys, and pigs. The decision came four years after the Center for Food Safety called on the FDA to remove the feed, but one brand remains on the market.
Despite repeated warnings from experts, the federal government under President Barack Obama has continued to allow farmers to pump livestock with antibiotics intended for humans, which has increased health risks for Americans.
A new study (pdf) from the Johns Hopkins Center for a Livable Future (JHCLF) blamed the lack of meaningful change in livestock-antibiotics policies on the agricultural and pharmaceutical industries, which have lobbied to block new laws and regulations from being adopted.
Members of Congress and officials with the Food and Drug Administration (FDA) have caved to industry pressures, even though evidence shows the overuse of antibiotics in livestock has made these drugs less effective in treating human infections.
Bob Martin, executive director of the JHCLF, told The Washington Post that FDA statistics reveal as much as 80% of the antibiotics sold in the U.S. are fed to cattle, pigs, chickens and other farm animals—a practice that reduces the efficacy of the drugs when it comes to fighting deadly infections in people.
Currently, about 23,000 patients die from antibiotic-resistant infections each year, according to the Centers for Disease Control and Prevention.
The Johns Hopkins study echoed the concerns of a 2008 report (pdf) on industry practices by a Pew Charitable Trusts commission of scientists that involved the Johns Hopkins Bloomberg School of Public Health. This earlier study also warned that the nation must back off on feeding antibiotics to animals.
The FDA has developed new guidelines that would require farms to stop using antibiotics specifically to bulk up food animals. But the rules would allow the drugs’ continued use for disease control. This latter provision is so loosely defined, Martin said, that there would be no practical change in the use of antibiotics.
“In a couple of areas, the Obama administration started off with good intentions. But when industry pushed back, even weaker rules were issued,” he told the Post. “We saw undue influence everywhere we turned.”
The new report was authored by a commission chaired by former Kansas governor John Carlin (D) and that included former U.S. agriculture secretary Dan Glickman, ranchers, and experts in public health and veterinary medicine.
The report’s message was echoed in a dire warning issued by Mary Wilson of the Harvard School of Public Health: “We will see common infections become fatal,” just as they were before the invention of antibiotics, she told the Post.
To Learn More:
Report: Feeding Antibiotics to Livestock is Bad for Humans, but Congress Won’t Stop It (by Melinda Henneberger, Washington Post)
Industrial Food Animal Production in America: Examining the Impact of the Pew Commission’s Priority Recommendations (John Hopkins Center for a Livable Future) (pdf)
FDA Quietly Ends Attempt to Regulate Antibiotics in Animal Feed (by Noel Brinkerhoff, AllGov)
80% of U.S. Antibiotics Go to Farm Animals (by Noel Brinkerhoff, AllGov)
Retired FDA investigator Patrick Stone (Katie Hayes Luke for ProPublica)
On the morning of May 3, 2010, three agents of the Food and Drug Administration descended upon the Houston office of Cetero Research, a firm that conducted research for drug companies worldwide.
Lead agent Patrick Stone, now retired from the FDA, had visited the Houston lab many times over the previous decade for routine inspections. This time was different. His team was there to investigate a former employee’s allegation that the company had tampered with records and manipulated test data.
When Stone explained the gravity of the inquiry to Chinna Pamidi, the testing facility’s president, the Cetero executive made a brief phone call. Moments later, employees rolled in eight flatbed carts, each double-stacked with file boxes. The documents represented five years of data from some 1,400 drug trials.
Pamidi bluntly acknowledged that much of the lab’s work was fraudulent, Stone said. “You got us,” Stone recalled him saying.
Based partly on records in the file boxes, the FDA eventually concluded that the lab’s violations were so “egregious” and pervasive that studies conducted there between April 2005 and August 2009 might be worthless.
The health threat was potentially serious: About 100 drugs, including sophisticated chemotherapy compounds and addictive prescription painkillers, had been approved for sale in the United States at least in part on the strength of Cetero Houston’s tainted tests. The vast majority, 81, were generic versions of brand-name drugs on which Cetero scientists had often run critical tests to determine whether the copies did, in fact, act the same in the body as the originals. For example, one of these generic drugs was ibuprofen, sold as gelatin capsules by one of the nation’s largest grocery-store chains for months before the FDA received assurance they were safe.
The rest were new medications that required so much research to win approval that the FDA says Cetero’s tests were rarely crucial.
Stone said he expected the FDA to move swiftly to compel new testing and to publicly warn patients and doctors.
Instead, the agency decided to handle the matter quietly, evaluating the medicines with virtually no public disclosure of what it had discovered. It pulled none of the drugs from the market, even temporarily, letting consumers take the ibuprofen and other medicines it no longer knew for sure were safe and effective. To this day, some drugs remain on the market despite the FDA having no additional scientific evidence to back up the safety and efficacy of these drugs.
By contrast, the FDA’s transatlantic counterpart, the European Medicines Agency, has pulled seven Cetero-tested medicines from the market.
The FDA also has moved slowly to shore up the science behind the drugs. Twice the FDA announced it was requiring drug makers to repeat, reanalyze or audit many of Cetero’s tests, and to submit their findings to the agency. Both times the agency set deadlines, yet it has allowed some companies to blow by them.
Today, six months after the last of those deadlines expired and almost three years after Cetero’s misconduct was discovered, the FDA has received the required submissions for just 53 drugs. The agency says most companies met the deadlines but acknowledged that “a few have not yet submitted new studies.”
Other companies, it said, have not submitted new research because they removed their drugs from the market altogether.
For its part, the FDA has finished its review of just 21 of the 53 submissions it has received, raising the possibility that patients are taking medications today that the agency might pull off the market tomorrow.
To this day, the agency refuses to disclose the names of the drugs it is reassessing, on the grounds that doing so would expose “confidential commercial information.” ProPublica managed to identify five drugs that used Cetero tests to help win FDA approval.
FDA officials defended the agency’s handling of the Cetero case as prudent and scientifically sound, noting that the agency has found no discrepancies between any original drug and its generic copy and no sign that any patients have been harmed.
“It is non-trivial to have to redo all this, to withdraw drugs, to alarm the public and the providers for a large range of drugs,” said Janet Woodcock, the director of the FDA’s Center for Drug Evaluation and Research. “There are consequences. To repeat the studies requires human experimentation, and that is not totally without risk.”
Woodcock added that an agency risk assessment found the potential for harm from drugs tested by Cetero to be “quite low,” an assessment she said has been “confirmed” by the fact that no problems have been found in the drugs the agency has finished reviewing.
She declined to release the risk assessment or detail its design. A subsequent statement from the agency described the assessment as “fluid” and “ongoing.” The FDA also has not released its 21 completed reviews, which ProPublica has requested.
Some experts say that by withholding so much information in the Cetero case the FDA failed to meet its obligations to the public.
“If there are problems with the scientific studies, as there have been in this case, then the FDA’s review of those problems needs to be transparent,” said David Kessler, who headed the FDA from 1990 to 1997 and who is now a professor at the University of California at San Francisco. Putting its reviews in public view would let the medical community “understand the basis for the agency’s actions,” he said. “FDA may be right here, but if it wants public confidence, they should be transparent. Otherwise it’s just a black box.”
Another former senior FDA official, who spoke on condition of anonymity, also felt the FDA had moved too slowly and secretively. “They’re keeping it all in the dark. It’s not transparent at all,” he said.
By contrast, the European Medicines Agency has provided a public accounting of the science behind all the drugs it has reviewed. Its policy, the EMA said in response to questions, is to make public “all review procedures where the benefit-risk balance of a medicine is under scrutiny.”
Woodcock dismissed comparisons to the EMA. “Europe had a smaller handful of drugs,” she said, “and they may not have engaged in as extensive negotiation and investigations with the company as we did.”
She said the FDA would have disclosed more, including the names of drugs, had it believed there was a risk to public health. “We believe that this did not rise to the level where the public should be notified,” she said. “We felt it would result in misunderstanding and inappropriate actions.”
In a written response to Kessler’s comments, the FDA said, “We’ve been as transparent as possible given the legal protections surrounding an FDA investigation of this or any type. The issue is not a lack of transparency but rather the difficulty of explaining why the problems we identified at Cetero, which on their face would appear to be highly significant in terms of patient risk, fortunately were not.”
Still, the FDA’s secrecy has had other ramifications. Some of Cetero’s suspect research made its way unchallenged into the peer-reviewed scientific literature on which the medical community relies. In one case, a researcher and a journal editor told ProPublica they had no idea the Cetero tests had been called into doubt.
Cetero, in correspondence with the FDA, conceded misconduct. And in an interview, Cetero’s former attorney, Marc Scheineson, acknowledged that chemists at the Houston facility committed fraud but said the problem was limited to six people who had all been fired.
“There is still zero evidence that any of the test results…were wrong, inaccurate, or incorrect,” he said. Scheineson called the FDA’s actions “overkill” and said they led to the demise of Cetero and its successor company.
In 2012, the company filed for Chapter 11 bankruptcy and emerged with a new name, PRACS Institute. PRACS, in turn, filed for bankruptcy on March 22 of this year. A PRACS spokesperson said the company had closed the Houston facility in October 2012.
Pamidi, the Cetero executive who provided the carts of file boxes, declined to comment.
As for Stone, the former FDA investigator, he said he was disturbed by the agency’s decisions.
“They could have done more,” he said. “They should have done more.”
‘We Should Have Been Told’
Cross-checking U.S. and European public records, including regulatory filings, scientific studies and civil lawsuits, ProPublica was able to identify a few of the drugs that are on the U.S. market because of tests performed at Cetero’s Houston lab (see chart.) There is no evidence that patients have suffered harm from these drugs; the FDA says it has detected no increase in reports of side effects or lack of efficacy among Cetero-tested medications.
To be sure, just because a crucial study is deemed potentially unreliable does not mean that a drug is unsafe or ineffective. What it does mean is that the FDA’s scientific basis for approving that drug has been undermined.
The risks are real, academic experts say, particularly for drugs such as blood thinners and anti-seizure medications that must be given at very specific doses. And generic versions of drugs have been known to act differently from name-brand products (see accompanying story.)
There is no indication the generic ibuprofen gelatin capsules hurt anyone, but their case shows how the FDA left a drug on the market for months without confirmation that the drug was equivalent to the name brand.
The capsules were manufactured by Banner Pharmacaps and carried by Supervalu, a grocery company that operates or licenses more than 2,400 stores across the United States, including Albertson’s, Jewel-Osco, Shop ‘n Save, Save-A-Lot, and Shoppers Food & Pharmacy.
Cetero had performed a key analysis to show that the capsules were equivalent to other forms of the drug. Banner, the drug’s maker, said the FDA first alerted it to the problems at Cetero in August 2011. The FDA required drug companies to redo many of Cetero’s tests, but, a spokesperson for Banner wrote in an email, “We received no directive from FDA to recall or otherwise interrupt manufacture of the product.”
Banner said it repeated the tainted Cetero tests at a different research firm, and the FDA said it received the new data in January 2012 — leaving a gap of at least five months when the FDA knew the drug was on the market without a rock-solid scientific basis.
An FDA spokesperson wrote in an email that the agency found the new studies Banner submitted “acceptable” and told Banner it had no further questions.
A spokesperson for Supervalu told ProPublica it purchased the ibuprofen from a supplier, which has assured the grocery company that “there are no issues with the product.”
According to U.S. and European records, another one of the drugs approved based on research at Cetero’s troubled Houston lab was a chemotherapy drug known as Temodar for Injection.
Temodar was originally approved in 1999 as a capsule to fight an aggressive brain cancer, glioblastoma multiforme. Some patients, however, can’t tolerate taking the medication orally, so drug maker Schering-Plough decided to make an intravenous form of the drug.
To get Temodar for Injection approved, the FDA required what it called a “pivotal” test comparing the well-established capsule form of Temodar to the form injected directly into the bloodstream.
Cetero Houston conducted that test, comparing blood samples of patients who received the capsule to samples of those who got the injection to determine if the same amount of the drug was reaching the bloodstream. This test is crucial, particularly in the case of Temodar, where there was a question about the right dosing regimen of the injectable version. If too little drug gets into the blood, the cancer could continue to grow unabated. If too much gets in, the drug’s debilitating side effects could be even worse.
Cetero performed the test between September 2006 and October 2007, according to documents from the European Medicines Agency, and FDA records indicate that same test was used to win approval in the U.S.
In 2011, the FDA notified Merck & Co., which had acquired Schering-Plough, about the problems with Cetero’s testing. In April 2012, the FDA publicly announced that analyses done by Cetero during the time when it performed the Temodar work would have to be redone. But according to Merck spokesman Ronald Rogers, the FDA has not asked Merck for any additional analyses to replace the questionable study.
The FDA declined to answer specific questions about the Temodar case, saying to do so would reveal confidential commercial information. But Woodcock said that in some cases, drug manufacturers had submitted alternative test results to the FDA that satisfied the agency that no retesting was necessary for specific drugs.
The FDA never removed Temodar for Injection from the market. The European Medicines Agency also kept the injection form of the drug on the market, but the two agencies handled their decision in sharply different ways.
The EMA has publicly laid out evidence — including studies not performed by Cetero — for why it believes the benefits of the injection drug outweigh its risks. But in the United States, the FDA has kept silent. To this day, Temodar’s label — the single most important way the FDA communicates the risks and benefits of medication — still displays data from the dubious Cetero study. (The label of at least one other drug, a powerful pain reliever marketed as Lazanda, also still displays questionable Cetero data.)
Woodcock said the agency hadn’t required manufacturers to alter their labels because, despite any question about precise numerical precision, the FDA’s overall recommendation had not changed.
In a written response to questions, Merck said it “stands behind the data in the TEMODAR (temozolomide) label.” The company said it learned about “misconduct at a contract research organization (CRO) facility in Houston” from the FDA and that it cooperated with investigations by the FDA and its European counterpart. It said that Cetero had performed no other studies for Merck.
Even one of the researchers involved in evaluating injectable Temodar didn’t know that the FDA had flagged Cetero’s analysis as potentially unreliable until contacted by a reporter for this story.
Dr. Max Schwarz, an oncologist and clinical professor at Monash University in Melbourne, Australia, treated some brain-cancer patients with the experimental injectable form of Temodar and others with the capsule formulation. Blood from his patients was sent to Cetero’s Houston lab for analysis.
Schwarz said he still has confidence in the injectable form of the drug, but said that he was “taken aback” when a reporter told him that the FDA had raised questions about the analysis. “I think we should have been told,” he said.
Suspect research conducted by Cetero Houston was not only used to win FDA approval but was also submitted to peer-reviewed scientific journals. Aided by the FDA’s silence, those articles remain in the scientific literature with no indication that they might, in fact, be compromised. For example, based on Cetero’s work, an article in the journal Cancer Chemotherapy and Pharmacology purports to show that Temodar for Injection is equivalent to Temodar capsules.
Edward Sausville, co-editor-in-chief of the journal, said in an email that the first he heard that something might be wrong with the Cetero research was when a reporter contacted him for this story. He also said the publisher of the journal would conduct a “review of relevant records pertinent to this case.”
‘There’s Always Something Missing’
During his years of inspecting the Houston lab, the FDA’s Stone said he often had the sense that something wasn’t right. When he went to other contract research firms and asked for data on a trial, they generally produced an overwhelming amount of paper: records of failed tests, meticulous explanations of how the chemists had made adjustments, and more.
Cetero’s records, by contrast, showed very clean, error-free procedures. As Stone and his colleagues dug through the data, though, they often found gaps. When pressed, Cetero officials would often produce additional data — data that ought to have been in the files originally handed over to the FDA.
Stone said, “We should have looked back and said, ‘Wait a minute, there’s always something missing from the studies from here. Why?’”
One reason, the FDA would determine, was that Cetero’s chemists were taking shortcuts and other actions prohibited by the FDA’s Good Laboratory Practice guidelines, which set out such matters as how records must be kept and how tests must be performed.
Stone and his FDA colleagues might never have realized Cetero was engaging in misconduct if a whistleblower hadn’t stepped forward.
Cashton J. Briscoe operated a liquid chromatography-tandem mass spectrometry device, or “mass spec,” a sensitive machine that measures the concentration of a drug in the blood.
He took blood samples prepared by Cetero chemists and used mass specs to perform “runs” — tests to see how much of a drug is in patients’ blood — that must always be performed with control samples. Often those controls show readings that are clearly wrong, and chemists have to abort runs, document the failure, recalibrate the machines, and redo the whole process.
But Cetero paid its Houston chemists based on how many runs they completed in a day. Some chemists doubled or even tripled their income by squeezing in extra tests, according to time sheets entered as evidence in a lawsuit filed in U.S. District Court in Houston by six chemists seeking overtime payments. Briscoe thought several chemists were cutting corners — by using the control-sample readings from one run in other runs, for example.
Attorney Scheineson, who represented Cetero during the FDA’s investigation, acknowledged that the Houston lab’s compensation system was “crappy” and that a handful of “dishonest” chemists at the Houston facility committed fraud.
In April 2009, Briscoe blew the whistle in a letter to the company written by his lawyer, reporting that “many of the chemists were manipulating and falsifying data.” Soon thereafter, Briscoe told the company that he had documented the misconduct. According to Stone and documents reviewed by ProPublica, Briscoe had photographic evidence that mass spec operators had switched the quality control samples between different runs; before-and-after copies of documents with the dates and other material changed; and information about a shadow computer filing system, where data from failed runs could be stored out of sight of FDA inspectors.
On June 5, apparently frustrated with Cetero’s response, Briscoe went a step further and called the FDA’s Dallas office. He agreed to meet Stone the following Monday, but never showed. Stone called him, as did other FDA officials, but Briscoe had changed his mind and clammed up.
Still, Stone’s brief phone conversation with Briscoe reminded the agent of all those suspiciously clean records he had seen at Cetero over the years. “Now that you have a bigger picture,” Stone recalled, “you’re like, ‘Oh, some of this stuff is cooked.’”
Two days after Stone’s aborted meeting with Briscoe, Cetero informed the FDA that an employee had made allegations of misconduct and that the company had hired an outside auditor to review five years’ worth of data. That led to months of back-and-forth between the agency and Cetero that culminated when Stone and his inspectors arrived in Houston in May 2010.
Two teams of FDA investigators eventually confirmed Briscoe’s main allegations and cited the company for falsifying records and other violations of Good Laboratory Practice. The net effect of the misconduct was far-reaching, agency officials wrote in a July 2011 letter:
“The pervasiveness and egregious nature of the violative practices by your firm has led FDA to have significant concerns that the bioequivalence and bioavailability data generated at the Cetero Houston facility from April 1, 2005, to June 15, 2010 … are unreliable.”
Bioequivalence studies measure whether a generic drug acts the same in the body as the name-brand drug; bioavailability studies measure how much drug gets into a patient’s system.
The FDA’s next step was to try to determine which drugs were implicated — information the agency couldn’t glean from its own records.
“We couldn’t really tell — because most of the applications we get are in paper — which studies were actually linked to the key studies in an application without asking the application holders,” the FDA’s Woodcock said. “So we asked the application holders,” meaning the drug manufacturers.
In the interim, the FDA continued to investigate processes and procedures at Cetero.
“We put their operations under a microscope,” said Woodcock. A team of clinical pharmacologists, statisticians and IT experts conducted a risk analysis of the problems at Cetero, she said, and they “concluded that the risk of a misleading result was very low given how the studies were done, how the data were captured and so forth.”
In April 2012, nearly three years after Briscoe first alerted the FDA to problems at Cetero, and nearly two years after Cetero handed over its documentation to inspectors, the FDA entered into a final agreement with the company. Drug makers would need to redo tests conducted at the company’s Houston facility between April 1, 2005 and Feb. 28, 2008, if those studies had been part of a drug application submitted to the FDA. If stored blood samples were still usable, they could be reanalyzed. If not, the entire study would need to be repeated, the FDA said. The agency set a deadline of six months.
Cetero tests done between March 1, 2008 and Aug. 31, 2009 would be accepted only if they were accompanied by an independent data integrity audit.
Analyses done after Sept. 1, 2009 would not require retesting. The FDA said that Cetero had issued a written directive on Sept. 1, 2009, ordering one kind of misconduct to stop, which was why it did not require any action on Cetero Houston studies after that date. According to public documents, however, the agency’s inspectors “found continued deficiencies” that persisted into December 2010.
In response to questions, the FDA said the problem period “was subsequently narrowed as more information regarding Cetero’s practices became available.”
A year after concluding its final agreement with Cetero, the FDA’s review is still not finished. “Without the process being public it’s hard to know, but it seems that this has been going on for too long,” said Kessler, the former FDA chief.
“The process has been long,” the FDA said, “because of the number of products involved and our wish to be thorough and accurate in both our requests for and our review of the data.”
Cetero’s attorney Scheineson said the FDA scaled back its requirements because it finally talked with company officials. He noted that Cetero had tried repeatedly to talk with the FDA before the agency issued its strongly worded July 2011 letter, and that more than 1,000 employees have since lost their jobs.
“If you would get an honest assessment from the leaders of the agency,” he said, “I think in retrospect they would have argued that this was overkill here and that they should have had input from the company before essentially going public with that death sentence.”
“I’m not sure what is meant by ‘death sentence,’” an FDA spokesperson wrote in response, “but our first priority was and is patient safety and we proceeded to conduct the investigation toward that objective.”
‘Should I Be Proud of This?’
The FDA’s Stone draws little satisfaction from unraveling the problems at Cetero.
There are thousands of bioequivalence studies done every year, he pointed out, with each study generating thousands of pages of paper records. “Do you really think we’re going to look at 100 percent of them? We’re going to look at maybe 5 percent if we’re lucky,” he said. “Sometimes 1 percent.”
Still, given how often he and other FDA teams had inspected the Houston lab, he thinks regulators should have spotted Cetero’s misconduct sooner.
“In hindsight I look back and I’m like, ‘Wow, should I be proud of this?’” he said. “It’s cool that I was part of it, but it’s crap that we didn’t catch it five years ago. How could we let this go so long?”
Research assistance for this story was contributed by Nick Stockton, Christine Kelly, Lily Newman, Joss Fong and Sarah Jacoby of the Science, Health, and Environmental Reporting Program at NYU.
WASHINGTON – Dairy industry groups have asked the Food and Drug Administration to be able to put artificial sweeteners in milk, and not change the label, claiming that it is so consumers can “more easily identify its overall nutritional value”.
The Food and Drug Administration is asking for data related to those sweeteners.
The International Dairy Foods Association (IDFA) and the National Milk Producers Federation (NMPF) filed a petition in 2009 requesting that the FDA amend its standard of identity for milk.
The petition asked the agency to allow the use of “any safe and suitable” sweetener for milk and asked to amend the standards of identity for 17 other milk and cream products.
Those products include sweetened condensed milk, whipping cream, yogurt and eggnog, which the groups say should be allowed to have “safe and suitable” sweeteners.
The groups request that the FDA “allow optional characterizing flavoring ingredients used in milk (e.g. chocolate flavoring added to milk) to be sweetened with any safe and suitable sweetener – including non-nutritive sweeteners such as aspartame.”
FDA regulations currently only allow milk products to contain “nutritive sweeteners” (those with calories) which the agency generally recognizes as safe.
The groups say the amendments “would promote more healthful eating practices and reduce childhood obesity by providing for lower-calorie flavored milk products.”
“They state that lower-calorie flavored milk would particularly benefit school children who, according to IDFA and NMPF, are more inclined to drink flavored milk than unflavored milk at school,” the FDA wrote in its notice.
The groups also say they would help with programs that aim to improve nutrition in school meals and argue that the proposed amendments would promote “honesty and fair dealing in the marketplace,” the FDA wrote.
The year 1999 was a good one for the drug company Merck. In its 64 page annual report, it predicted that the arthritis medicine Vioxx (“Our Biggest, Fastest, and Best Launch Ever!”) would also prevent Alzheimer’s disease and colon cancer. It announced it was seeking approval to market the asthma drug Singulair to two-year-olds. And it forecast that 40 million women would take its new osteoporosis drug, Fosamax, as Merck continued to “help educate both doctors and patients” about the bone disease.
It turned out Merck spoke too soon. Vioxx was withdrawn in 2004 for doubling stroke and heart attacks in long-term users; Singulair now carries FDA warnings about “neuropsychiatric events” and Fosamax is suspected of doubling the risk of esophageal cancer, causing bone fractures instead of preventing them and causing heart problems, intractable pain and jawbone death. Oops!
There’s plenty of ka-ching in selling “strong bones” products for the same reason there was plenty of ka-ching in selling “hormone replacement” products: one-half the population is female, and no one wants to look old. Of course, “avoiding hot ﬂashes” really means “still looking hot” in hormone marketing terminology, and “avoiding fractures” really means “still looking hot” in bone product marketing lingo. That’s why attractive women like Meredith Vieira from the Today show and former Charlie’s Angel Cheryl Ladd and actress Sally Field push bone drugs, just as model Lauren Hutton pushed hormone replacement therapy.
To cash in on Fosamax, the first in the bisphosphonate bone drug class, Merck decided to market the dangers of osteoporosis “far beyond ailing old ladies.” It hired researcher Jeremy Allen to whip up fears of “osteopenia,” the risk of osteoporosis, as a health epidemic to sell bone drugs and planted bone scan machines in medical offices across the country, says National Public Radio. Allen created the faux “Bone Measurement Institute” which also maneuvered Medicare reimbursement for the scans. By 1999, there were 10,000 bone scan machines in medical offices, said the Associated Press, when there had been only 750 before Fosamax.
Like its trouble-laden drug Vioxx, Merck’s Fosamax ﬂew out of the FDA. It received only a six month review before its 1995 FDA approval. (The government also helped its promotion with the HHS secretary herself, Donna Shalala, participating in a 1998 rally kicking off free bone density screenings to be offered in 100 cities.)
But the wheels soon came ﬂying off the bone drug. Patients experienced esophageal “irritation” and the warning to stay upright for one full hour after taking Fosamax, eating or drinking nothing was added after approval. One woman who took Fosamax but remained upright for only 30 minutes, not 60, had to be admitted to the Mayo Clinic with “severe ulcerative esophagitis affecting the entire length of the esophagus” and had to be fed intravenously, according to the New England Journal of Medicine.
Next, dentists and oral surgeons discovered after simple tooth extractions and other in-ofﬁce dental work, the jawbone tissue of patients on bisphosphonates would sometimes not heal but become necrotic and die — a condition called osteonecrosis of the jaw(ONJ), The necrotic condition did not take long to manifest “even short-term oral use of alendronate [Fosamax] led to ONJ in a subset of patients” — wrote a dental journal, but it somehow slipped through Fosamax’s two, three-year clinical trials on which its FDA approval was based. Doctors, dentists, and pharmacists were enraged at what looked like deliberate obfuscation by Merck.
And there were second, third and fourth opinions about Fosamax! According to an FDA epidemiologist writing in New England Journal of Medicine in 2009 there were 23 incidences of Fosamax-associated esophageal cancer in the US and eight deaths and 27 incidences of cancer in Europe and Japan and six deaths.
Next reports in medical journals linked bisphosphonates to the risk of developing atrial ﬁbrillation, or a chronically irregular heartbeat and to severe bone, joint or muscle pain. “In the most serious cases, the pain was so severe that patients could not continue their normal activities,” wrote the FDA in a press release. “Some patients have complete relief of symptoms after they stop taking the drug, while others have reported slow or incomplete resolution.” Clearly, the FDA was trying hard to avoid the word irreversible.
Finally, in a development that suggests tremendous medical ineptitude if not duplicity, bisphosphonates were found to sometimes cause the very fractures they were supposed to prevent. The thigh bones of patients on bisphosphonates have “simply snapped while they were walking or standing,” after “weeks or months of unexplained aching,” reported the New York Times in an article called “Drugs to Build Bones May Weaken Them.”
It should be embarrassing to the medical establishment that a prominent drug company and the FDA “discovered” severe side effects after years of patient use and that bone scans are still merchandised though they are of no value to 90 percent of women, according to the New England Journal of Medicine. It should be further embarrassing that Merck was allowed to make $3 billion a year off a drug that many say would not have been approved had clinical trials lasted longer. Its patent expired in 2008.
Now Merck is about to launch a new drug for osteoporosis called odanacatib which has already intrigued the money men on Wall Street. “Odanacatib may be a viable alternative for patients who need continued therapy and who want benefits beyond what they received from bisphosphonates,” a senior Merck research executive told Reuters without a hint of irony.
Martha Rosenberg is a columnist/cartoonist who writes about public health. Her first book, titled Born with a Junk Food Deficiency: How Flaks, Quacks and Hacks Pimp the Public Health, has just been released by Prometheus Books. She can be reached at: email@example.com.
- New Study Links Fosamax to Esophageal Cancer (prweb.com)
- New Study Links Fosamax to Vision Problems Risk (prweb.com)
- Intramedullary Nailing Surgery Is Successful Treatment For Patients With Femur Fractures From Use Of Fosamax Or Other Bisphosphonates (drug-injury.com)
- Alendronate Oral May Posses Bad Side Effects (businesslawdaily.net)
Barack Obama’s administration has launched attacks unparalleled since the McCarthy years on those who blow the whistle against corruption inside the federal government.
Obama has already charged more whistleblowers under the Espionage Act than all previous administrations combined (as reflected in the list below.) Peter van Buren, a career foreign affairs officer at the Department of Department of State claims his job was threathened after writing, We Meant Well: How I Helped Lose the Battle for the Hearts and Minds of the Iraqi People. Van Buren, who became disillusioned by waste and hypocrisy while serving in Iraq, says “The number of cases in play [against whistleblowers] suggests an organized strategy to deprive Americans of knowledge of the more disreputable things that their government does. How it plays out in court and elsewhere will significantly affect our democracy.”
Van Buren points out that the pre-World War 1 Espionage Act has been used against “labor leaders and radicals like Eugene V. Debs, Bill Haywood, Philip Randolph, Victor Berger, John Reed, Max Eastman, and Emma Goldman. Debs, a union leader and socialist candidate for the presidency, was sentenced to 10 years in jail for a speech attacking the Espionage Act itself. The Nixon administration infamously (and unsuccessfully) invoked the Act to bar the New York Times from continuing to publish the classified Pentagon Papers.” But no other administration has used this legislation as liberally as President Obama who has authorized more drone attacks than any other American president.
Van Buren was writing on the blog Tom.Dispatch.com of Tom Engelhardt, a teaching fellow at the Graduate School of Journalism at the University of California. Engelhardt in turn observes: “One thing is obvious. No one ever joins the government in order to be a whistleblower or leaker.Whistleblowers are created, not born,” speaking words that resonate with my experience as a whistleblower. Van Buren notes: “It is perhaps typical of whistleblowers and leakers that something they are privy to simply pushes them over the edge.” In my case it was the realization that government was failing to act against a U.S. multinational whose mining practices were leading to the injury and deaths of South African vanadium miners.
I continue to speak out against injustice, but it certainly has not made my life easier. Each week I get mails to my Facebook site from those who are whistleblowers or are close to whistleblowers. This week’s example is typical: “I know you don’t know me and I am taking a HUGE chance by writing you, but I have to at least try. My parents are going through some of the same things you went through at the EPA. Both top-level executives at federal agencies they have been retaliated harshly against. NO ONE seems to hear us. I’m begging for your help. Please help us… These agencies are corrupt and we are still on the bus fighting like Rosa.”
There is little I can do other than direct them to the National Whistleblower Center, give the names of lawyers and share a little human empathy. But there is no doubt that under this administration there is a concerted attack against those who dare to expose corruption in government or corporations.
Recently four employees of the Air Force Mortuary in Dover, Delaware, revealed that the Dover Air Force Base mortuary had lost and sawed off body parts and mishandled other remains of America’s war dead. Retaliation against them included firings, the placing of employees on indefinite administrative leave, and the imposition of five-day suspensions. Special Counsel Carolyn Lerner has accused the Air Force of deflecting blame — and a mortuary official of lying and obstructing the probe by firing one of the workers who blew the whistle. What remains to be seen is whether Lerner, an Obama political appointee, will distinguish herself from her disgraced predecessor by seriously investigating corruption under this administration.
At present six whistleblowers are suing the Food and Drug Administration for electronically spying on them when they tried to alert Congress about misconduct at the agency. This is the agency tasked with overseeing public health, food safety, medicines and medical devices. Senator Charles E. Grassley (R-Iowa) launched an investigation in response to a lawsuit filed by six FDA whistleblowers and documents released by the National Whistleblowers Center that show the FDA targeted whistleblowers for special monitoring and intercepted personal communications to Congress, including emails to Senator Grassley’s staff. Senator Grassley, the Ranking Member of the Senate Judiciary Committee asked FDA Commissioner Margaret Hamburg whether or not whistleblowers were singled out for special monitoring based on a letter they wrote to President-Elect Obama’s Transition Team.
We are waiting to see the Army’s reaction to whistleblower Lieutenant Colonel Daniel Davis, who documented in the Armed Forces Journal that senior leaders of the Department of Defense intentionally and consistently misled the American people and Congress about success in the Afghan War.
Those charged under the Espionage Act include:
- Former CIA officer John Kiriakou charged on January 23 for disclosing classified information to journalists about the waterboarding of al-Qaeda suspects. The CIA also found an excuse to fire his wife, also employed by the Agency, while she was on maternity leave.
- Thomas Drake an employee of the National Security Agency revealed that it spent $1.2 billion on a contract for a data collection program called Trailblazer when the work could have been done in-house for $3 million. Drake’s home was raided at gunpoint and the agency forced him out of his job. He now works at an Apple Store. His attorney told Anti-war.com: “Too often, whistleblowers end up broken, blacklisted, and bankrupted.”
- Whistleblower Pvt. Bradley Manning, accused of leaking Army and State Department documents to the website WikiLeaks, spent more than a year in a U.S. Marine prison and was denied the chance even to appear in court to defend himself until almost two years after his arrest.
- Former chief military prosecutor at Guantanamo Morris Davis lost his career as a researcher at the Library of Congress for writing a critical op-ed for the Wall Street Journal and a letter to the editor at the Washington Post on double standards at the infamous prison.
- Robert MacClean was charged for blowing the whistle on the Transportation Security Administration.
Van Buren notes in his piece for Tom.Dispatch.Com “My travel vouchers from as far back as the law allows have come under “routine” re-examination. My Internet activity is the subject of daily reports. My credit reports have been examined for who knows what. Department friends who email me on topical issues have been questioned by agents of Diplomatic Security, the State Department’s internal police. My Freedom of Information Act request for documents to help defend myself and force State to explain its actions has been buried.”
And then we read investigative reports in the Washington Post, as an example, of 33 members of Congress that have steered more than $300 million in earmarks and other spending provisions to dozens of public projects that are next to or within about two miles of the lawmakers’ own property. We have yet to hear of action against them.
Freedom of the press and freedom of expression are American constitutional bulwarks. These important elements of the constitution provide protection for truth-tellers as the last defense against tyranny. It is a shame that a legacy of the first African American president is heightened repression against whistleblowers.
See Marsha on C-Span Book/TV at: www.marshacoleman-adebayo.org.
Dr. Marsha Coleman-Adebayo is the author of No FEAR: A Whistleblowers Triumph over Corruption and Retaliation at the EPA is available through amazon.com and the National Whistleblower Center. Dr. Coleman-Adebayo worked at the EPA for 18 years and blew the whistle on a US multinational corporation that endangered vanadium mine workers. Marsha’s successful lawsuit lead to the introduction and passage of the first civil rights and whistleblower law of the 21st century: the Notification of Federal Employees Anti-discrimination and Retaliation Act of 2002 (No FEAR.)
- Whistleblower Lawsuit Puts Spotlight On FDA Technical Reviews (news.sciencemag.org)
- Inside President Obama’s War On The Fast & Furious Whistleblowers (forbes.com)
- Scientists suing the FDA after covert surveillance (newscientist.com)