Tag: FDA

04/8/15

Sola Fide with Drugs

© Awakenedeye | Dreamstime.com
© Awakenedeye | Dreamstime.com

Between May of 1999 and July of 2002, a researcher employed at the Stratton Veterans Affairs Medical Center in Albany New York falsified documents in a clinical trial drug study that contributed to the death of a subject. The researcher “knowingly and willfully” misrepresented the results of a blood chemistry analysis to qualify an individual with impaired kidney and liver function for the study. As Charles Seife reported, the study subject died as a direct consequence of the first dose of the treatment. “The researcher pleaded guilty to fraud and criminally negligent homicide and was sentenced to 71 months in prison.”

Although this episode is described in detail in FDA documents as well as court documents,none of the publications in the peer-reviewed literature associated with the chemotherapy study in which the patient died have any mention of the falsification, fraud, or homicide. The publications associated with 2 of the 3 other studies for which the researcher falsified documents also do not report on the violations.

This was just one of the four case examples described by Seife in his JAMA Internal Medicine article, “Research Misconduct Identified by the US Federal Drug Administration.” His study sought to identify publications describing clinical trials to which the FDA had given its severest warning (an OAI—official action indicated—warning) after doing routine inspections. Once the published articles were identified, Seife tried to determine if there was any subsequent acknowledgement of the violation.

From the documents he and his students gathered together, they found approximately 600 clinical trials mentioned as potentially having OAI violations. They then submitted requests for the FDA OAI notifications through the Freedom of Information Act. Because of extensive redactions (censoring for legal or security purposes), most of the trials in the documents could not be identified. When key information was available, they were able to identify 101 trials with one or more OAI grades. From these, they were able to glean 57 trials with 1 or more FDA inspections of a trial site with evidence of “significant departure from good clinical practice.” These violations included actions such as: underreporting adverse events, violations of protocol, violations of recruitment guidelines, and various forms of scientific misconduct.

In 22 of these trials (39%), the FDA cited researchers for falsification or submission of false information; in 14 (25%), for problems with adverse events reporting; in 42 (74%), for failure to follow the investigational plan or other violations of protocol; in 35 (61%), for inadequate or inaccurate recordkeeping; in 30 (53%), for failure to protect the safety, rights, and welfare of patients or issues with informed consent or institutional review board oversight; and in 20 (35%), for violations not otherwise categorized. Examples of uncategorized violations include cases in which the investigators used experimental compounds in patients not enrolled in trials, delegated tasks to unauthorized personnel, or otherwise failed to supervise clinical investigations properly.

The 57 clinical trials in their study had resulted in 78 articles published in peer-reviewed journals. “Of these 78 articles, only 3 publications (4%) included any mention of the FDA inspection violations despite the fact that for 59 of those 78 articles (76%), the inspection was completed at least 6 months before the article was published.”

This led Seife to conclude in: “Are Your Medications Safe?” that for more than a decade, the FDA has shown a pattern of burying the details of scientific fraud and misconduct. “The agency doesn’t notify the public, the medical establishment, or even the scientific community that the results of a medical experiment are not to be trusted.” So no one finds out which data is bogus; “which drugs might be on the market under false pretences.” The FDA has repeatedly hidden evidence of scientific fraud from the public, from its trusted scientific advisors—even as they were attempting to decide whether or not a new drug should be allowed on the market. They even stonewalled a congressional panel investigating a case of fraud regarding a dangerous drug.

The sworn purpose of the FDA is to protect the public health, to assure us that all the drugs on the market are proven safe and effective by reputable scientific trials. Yet, over and over again, the agency has proven itself willing to keep scientists, doctors, and the public in the dark about incidents when those scientific trials turn out to be less than reputable. It does so not only by passive silence, but by active deception. And despite being called out numerous times over the years for its bad behavior, including from some very pissed-off members of Congress, the agency is stubbornly resistant to change. It’s a sign that the FDA is deeply captured, drawn firmly into the orbit of the pharmaceutical industry that it’s supposed to regulate.

Seife’s research and conclusions are disturbing on so many levels. The FDA knows about dozens of scientific papers whose data are questionable, but the agency had said and done NOTHING. Even when itself is “shocked at the degree of fraud and misconduct in a clinical trial.” Seife said the most common excuse given by the FDA is that revealing which drugs’ approval relied upon tainted data, would compromise “confidential commercial information” that could hurt the drug companies if it was revealed. Another excuse is that the FDA doesn’t want to confuse the public by revealing misconduct that in the FDA’s judgment, doesn’t “pose an immediate risk to public health.”

The FDA wants you to take it on faith that its officials have the public’s best interest at heart. Justification through faith alone [sola fide] might be just fine as a religious doctrine, but it’s not a good foundation for ensuring the safety and effectiveness of our drugs.

03/30/15

Killer Caffeine

© : Santi Sinsawad | 123RF.com
© : Santi Sinsawad | 123RF.com

I knew of a woman who had a dual addiction to marijuana and caffeine. Yes, caffeine. She drank several pots of coffee throughout the day along with smoking marijuana. While a resident in a long-term rehab for women, she repeatedly denied that she had caffeinated coffee. But the staff “knew” she was somehow getting it and using it because of the coffee stains on the rug in her room. Several room searches were done to no avail. Finally she was busted. What the woman had done was smuggle a Melita filter and caffeinated coffee into the facility when she out for an appointment. In all the years I’ve worked with substance use/abuse disorders, this was the only time I’d ever seen such classic addictive behaviors with caffeine.

The last several years have seen the marketing of energy drinks with high caffeine content, and the use of products like 5-hour ENERGY “shots.” Many of the individuals I meet in early recovery are drawn to energy drinks, so I’ve been watching for news and research on them. I’ve heard of some concerns about their safety. And recently I heard about powdered caffeine. Just one teaspoon contains 3,200 mg of caffeine.

So let’s start with some basic information about caffeine before we get to the reported deaths from using caffeine powder. According to Wikipedia, caffeine is the world’s most widely consumed psychoactive drug. It is legal and unregulated in most countries worldwide. In North America, 90% of adults consume caffeine daily. I am one of them. A seven-ounce cup of coffee contains 80 to 175 mg of caffeine, depending upon how it is prepared (drip, percolation or espresso). Toxic doses of caffeine for an adult are over 10 grams—twenty times higher than the average consumption of 500 mg per day.

Caffeine’s positive effects have to do with reducing fatigue and preventing drowsiness. It can even stimulate faster and clearer thought flow, increased focus and better general body coordination. Consistent with this last effect, moderate doses of caffeine can improve athletic performance, but the improvements are not usually substantial. There can be some undesired effects, such as mild anxiety, insomnia, and jitteriness. Although there are caffeine-induced disorders in the DSM-5, caffeine use is usually not considered to be addictive.

Caffeinism can occur when 400 to 500 mg at one time, or 1,000 to 1,500 mg per day or more of caffeine is consumed. Winston et al. noted that the symptoms that occur (restlessness, agitation, excitement, rambling thought and speech, and insomnia) overlap with those of several psychiatric disorders. Extreme overdose can result in death. The estimated lethal dose in humans is estimated to be equivalent to 150 to 200 milligrams per kilogram of body mass; the caffeine in roughly 80 to 100 cups of coffee for an average adult. You can read further about caffeine in a 1981 article, “Caffeine: Psychological Effects, Use and Abuse.” As always with psychoactive substances, you can also see what Erowid has to say about caffeine.

Now, let’s look at caffeine powder. In May of 2014, 18-year-old Logan Stiner died after ingesting 23 times the amount of caffeine found in a typical cup of coffee. Given the above noted information, Logan would have consumed 1,850 to 4,025 mg of caffeine.  While the estimated lethal dose given above would seem to be higher than Logan’s intake of caffeine powder, he still clearly consumed roughly four to eight times the dose needed for caffeinism. Several reports have indicated that a teaspoon of caffeine powder, the equivalent of 25 cups of coffee, can be lethal. Logan’s use of caffeine powder did approach that level. Caffeine powder is a pure chemical. And as Mary Clare Jalonick reported:  “the difference between a safe amount and a lethal dose is very small.”

The FDA has warned against the use of powered pure caffeine. They are particularly concerned about Internet sales of bulk bags of it. “Pure caffeine is a powerful stimulant and very small amounts may cause accidental overdose. Parents should be aware that these products may be attractive to young people.” Michael Landa, the Director of FDA’s Center for Food Safety and Applied Nutrition, reported having a December 2014 meeting with Logan’s parents and the parents of a 24-year-old who died after ingesting powdered caffeine. He said:

I cannot say strongly enough how important it is to avoid using powdered pure caffeine. The people most drawn to it are our children, teenagers, and young adults, especially students who want to work longer to study, athletes who want to improve their performance, and others who want to lose weight.

The FDA doesn’t have the legal authority to just pull these products off the shelf. Caffeine powder is sold as an unregulated dietary supplement—unlike caffeine added to soda and other drink products. This is a common way of getting around regulation with several other potentially harmful psychoactive substances (see Krypton Can Kill You; Kava is not a Magic Bullet).

Michael Taylor, the FDA’s deputy commissioner of foods, said it was inherently irresponsible to market such a potentially dangerous product. “I would hope that people would get the message that they just ought to stop selling it.” So far, they don’t seem to be getting that message.

David Templeton, of the Pittsburgh Post-Gazette, reported that six senators have sent a letter to the FDA urging them to ban the retail sale of caffeine powder. The letter stated that pure caffeine is unsafe. Overdosing is easy and virtually unavoidable. Powered caffeine sold in bulk was said to be markedly different than other caffeine products, on the market, such as energy drinks, energy shots and others. “Because of the risk powdered caffeine poses to consumers, these products merit swift and significant action by the FDA.” The Council of Responsible Nutrition, a trade association for the supplement industry, recently stated their support for an FDA ban against the retail sale of caffeine powder. NutraKey, a major online marketer of caffeine powder did not respond to requests for comment.

09/24/14

The Making of an American Tragedy

image credit: iStock
image credit: iStock

Psychiatrist Peter Breggin said that diagnosing millions of children with ADHD and then treating them with stimulants and other psychoactive chemicals is an American tragedy. “Never before in history has a society attempted to deal with its children by drugging a significant portion of them into conformity while failing to meet their needs in the home, school and society.” According to Dr.Breggin, the ethical scientist and physician, the concerned parent “must feel stricken with grief and dumbfounded” that our society has allowed this to happen to our children.

In October of 2011, the American Academy of Pediatrics (AAP) overrode the FDA and approved diagnosing children as young as four with ADHD and medicating them with Ritalin. The lead author of the report said: “Because of greater awareness about ADHD and better ways of diagnosing and treating this disorder, more children are being helped.” Dr. Breggin said this action was an outrage: “This endorsement of drugging younger children by the American Academy of Pediatrics is an outrage.”

According to Dr. Breggin, the scientific literature shows that 50 percent or more of children this young will become depressed, lethargic, weepy—along with being more manageable when given medications such as Ritalin, Adderall and other ADHD medications. Studies show that stimulants will permanently change brain chemistry in the children, cause shrinkage of brain tissue and predispose them to cocaine addiction in young adulthood. He also feared this endorsement by the AAP would open the door for every other psychiatric drug being prescribed to children that young.

These new guidelines will encourage prescribers to throw caution to the wind with toddlers, opening a Pandora’s box of drug intervention for children. Many young children will have their brains bathed with powerful and often toxic chemicals in the early years of their central nervous system development.

But the problems didn’t stop there. Susanna Visser, who oversees the CDC research on ADHD, presented a report at the Georgia Mental Health Forum in May of 2014 that suggested at least 10,000 2 and 3 year-olds were being medicated for ADHD. “It puts these children and their developing minds at risk, and their health is at risk.” Effective non-drug treatments were often ignored.

Families of toddlers with behavioral problems are coming to the doctor’s office for help, and the help they are getting too often is a prescription for a Class II controlled substance, which has not been established as safe for that young of a child.

As liberal as the AAP guidelines for ADHD are, they do not even address diagnosis in children 3 and younger—let alone the use of stimulant medications—with that age group. Children under 4 are not covered in the guidelines because “hyperactivity and impulsivity are developmentally appropriate for toddlers.” Dr. Lawrence Diller, a pediatrician, said: “People prescribing to 2-year-olds are just winging it. It is outside the standard of care, and they should be subject to malpractice if something goes wrong with a kid.”

Sheila Matthews attempted to put “the insanity of drugging 2-3 year olds” in perspective. She noted that the average weight for male toddlers at three years was 29.5 pounds; female toddlers averaged 28.4 pounds. “By this age, only 80 percent of the child’s brain has fully developed.” Kids at this age are learning to arrange things in groups, to put things in size order, remembering what they did yesterday, learning to say please and thank you, and recognizing themselves in the mirror. “In a nutshell, 2-3 year old toddlers are being labeled with an alleged mental illness that is not based in science or medicine and then “treated” with extremely addictive, mind-altering drugs before their brains are even fully formed.”

Psychiatrist Allen Frances said: “Treating babies with stimulants is based on no research, is reckless, and takes no account of the possible harmful long-term effects of bathing baby brains with powerful neurotransmitter drugs.” He hoped that the CDC report would fuel a backlash of parental and professional protest as it becomes clearer how absurdly overused is the ADHD diagnosis and stimulant medication. “It is also particularly outrageous that so many of the thought leaders promoting the excessive use of stimulants have such close ties with pharmaceutical companies.”

Dr Breggin lamented that instead of meeting the normal needs of our children, we are suppressing them with drugs. The average parent or teacher has no idea that what is presented as medical treatment “is actually a form of medical child abuse.” What they see is a more manageable child and assumes this is for the best. Instead, it is the making of an American tragedy.