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Wall Street Journal
Arnold William Klein, M.D. response to "Allergan Now Batting. 500 in Botox Lawsuits" in the Wall Street Journal's Health Blog
http://blogs.wsj.com/health/2010/05/12/allergan-now-batting-500-in-botox-lawsuits/
As the individual responsible for winning the first Botox lawsuit as Judge Chavez would agree I no longer trust much of the information that Allergan provides. For many years Alastair and Jean Carruthers served as their main consultants and demonstrated Botox injection through out the USA. Unfortunately they were from Canada and had neither a green card nor any license to inject in the USA. Tbey published many papers including one regarding the dilution of Botox that
stated dilution of the toxin did not matterr. Being a reviewer of this paper I discovered they had altered their data to reach this coclusion.I brought this to the attention of the head of Allergan and was subsequently fired as a consultant. In July of that same year a confidential report made to Allergan by a consulting firm showed 207 patients had developed severe medical problems associated with the spread of toxin, including several deaths. A third of the cases reported occurred in people treated for wrinkles. One not blame the toxin for the problems. Having been the one who developed the dilution and injection points that resulted in FDA approval of this product for the frown I firmly believe in its uae. Additionally, I have published both in Science and The New England journal of Medicine concerning its use. Who cannot be trusted is Allergan and their present band of cosmetic consultants who have actively prevented me from speaking at medical meetings and allowed the publication of misleading data. Furthermore be cautious on the use of all the new toxins in that the literature surrounding their applcation is often of questionable integrity. Arnold William Klein MD ,Professor of Dermatology and Medicine at the David Geffen School of Medicine at UCLA
- 12:32 am May 28, 2010
- Arnold William KleinMD wrote:
A physician asks does Allergan educate physicians for the use of their product Botox for off-label purposes. Take for example cerebral palsy in children when it is not approved for this indication? Allergan, through its extensive chain of paid consultants, has created a vast array of courses they sponsor through assorted CME (Continuing Medical Education) programs. This is not widely known outside of a select medical community. The FDA has seemingly turned a blind eye toward Allergan’s off-label promotion of this drug for a myriad of purposes.
In the deposition for a trial in orange county concerning the death of a 7 yo child from Botox treatent for cerebral palsy , the treating physician (Dr X) stated that he went to two Allergan-sponsored symposiums to learn how to treat cerebral palsy in children with Botox®. Indeed, Allergan has been known to pay the travel expenses of physicians to attend such meetings. While the physician named in this suit is not a neurologist, he was trained to use Botox® in cerebral palsy by a pediatric neurologist. Would you not think training of this type be best left to training other pediatric neurologists? He was taught to use a dose of Botox® in treating children which in reality is twice the maximum dose. What makes no sense is that even though sales representatives of Allergan visited the physician’s office over 50 times; maximum dosing was never discussed nor was why the patient was hospitalized 10 times for difficulties breathing while undergoing Botox® therapy. This is a well known side-effect which occurs with spread of a botulism based toxin. Why was the treating physician unaware of this sign that the toxin had spread? Was he unaware that death can happen as a complication if you have severe problems with swallowing or breathing after treatment?
What is even stranger is that, according to Mitchell Brin, Vice-President of Allergan for Botox®/Neurology, the company has never shared its maximum dosage information with physicians due to a federal ban on marketing for non-approved uses. What is meant by maximum dose is even confusing. Some individuals consider the maximum dose in cerebral palsy to be 400 units per visit. However, the child’s weight, muscle mass and acute nature of the illness will modify this dose. So the idea of a maximum dose for a specific condition is indeed variable and physicians should be aware that there are no specific rules, but rather the physician must understand the toxin, the disease and various factors that determine the treating dose to be used in a given patient. So, apparently, Allergan can teach physicians how to treat cerebral palsy with Botox® but not how to treat it safely? Furthermore, there is literature which supports the use of low-dose rather than high-dose toxin in treating cerebral palsy. Was Dr X aware of this or the fact that low volume with precise injections produces the best results? Maybe he believed volume does not matter in that it has been printed in a journal? Whatever this physician knew it was not enough to use the Toxin safely.Even for cosmeic use there have been problems when it has used in areas such as the neck even in small doses.
The FDA has also turned a blind eye to Allergan teaching use in this location. All I can say is it not time for the FDA to wake up to a company more interested in selling a product than teaching people to use it safely
Things Get Ugly Over a Beauty Injection
Maker of Antiwrinkle Shot, Famed Skin Doctor Face Off Over New Product's Safety
WALL STREET JOURNAL
By RHONDA L. RUNDLE
August 29, 2007;
Diane Goostree had come to Arnold W. Klein's beach house overlooking the Pacific Ocean to try to dissuade the skin doctor to the aging rich and famous from leading a campaign to have her company's wrinkle-smoothing product, ArteFill, banned.
As they sipped flavored water in Laguna Beach, Calif., she laid out data that had persuaded the Food and Drug Administration to approve the amalgam of calf collagen and microscopic plastic beads that is injected into the face to permanently fill creases. But at the end of the calm exchange, the flamboyant 62-year-old Beverly Hills dermatologist remained "unimpressed," still worried that ArteFill and products like it could "destroy" the medical field he helped pioneer.
"There wasn't anything that showed the biological reaction of this stuff under the skin," Dr. Klein says. For her part, Ms. Goostree, chief executive of Artes Medical Inc., says his concerns are based on "inaccurate, out-of-date and/or incomplete information."
Dr. Klein has become the loudest voice in the hottest debate in the small world of cosmetic dermatology: How safe is a new wave of antiwrinkle shots that -- unlike their predecessors -- are long-lasting or even permanent? At medical conferences in recent months, doctors have bickered over whether these products receive rigorous enough testing to gain FDA approval. Products like ArteFill are considered implanted medical devices, not drugs, and undergo a different approval process because, unlike drugs, they are believed to basically be inert fillers, leaving bodily processes unchanged. Some doctors, however, believe that the effects of these products on tissue need to be studied before they are approved because unlike earlier facial injections -- such as Restylane, a device, or Botox, a drug -- these treatments don't just wear off in four to six months.
As Ms. Goostree points out, though, the only clinical study anyone can point to is the Artes study relied on by the FDA. An update, she adds, recently showed patients injected by properly trained physicians continue to do well after five years. "We have confidence in our product and in the FDA process that approved it as safe and effective," she says.
That hasn't stopped Dr. Klein, who has recruited like-minded, high-profile physicians and hired DBC Public Relations Experts in Washington to help spread his concerns. Dr. Klein says the longer duration of the new products comes with the risk of unsightly lumps that could require surgical removal and leave ugly scars -- something Ms. Goostree says doesn't happen when ArteFill is injected properly.
Dr. Klein and seven other physicians are asking the FDA for a public hearing to re-examine ArteFill's safety, even though the agency approved it in October. A letter from them, hand-delivered to the FDA commissioner in July, says ArteFill "may pose immediate, debilitating and disfiguring health risks."
Dermatologist Amy N. Newburger, who was part of an FDA panel that recommended ArteFill's approval, has sent a less strident letter. In an interview, Dr. Newburger says she wants the FDA to toughen its review process for aesthetic devices. "There needs to be a paradigm shift in the process so that people will know what risks they are embracing." Scores of emerging injectable fillers will be coming to the FDA, she says. Dr. Newburger practices in Scarsdale, N.Y. and says she doesn't have financial ties to industry.
Daniel Schultz, director of the FDA's Center for Devices and Radiological Health, says he is aware of only one adverse event caused by ArteFill. But he said that in response to "a small number of physicians' complaints," the agency has set up a team to examine the post-marketing experience of all dermal fillers. While the size of required human tests of such devices is usually smaller than those for drugs, he says, the approval process "is very, very similar."
The role of physicians who become activists, like Dr. Klein, is complicated in a world where doctors often are paid by companies to perform scientific research and teach others how to use their products. In this case, Dr. Klein has past and current ties to ArteFill competitors. From 2000 until last April, Dr. Klein worked for Allergan Inc., which sells Botox and Juvederm, and since 2004 he has been a consultant to Restylane maker Medicis Pharmaceuticals Corp. Dr Klein, who made $250,000 a year from Allergan for several years, says such ties "have nothing to do whatsoever" with his concerns about ArteFill. "I refuse to see the field of soft-tissue augmentation destroyed," he says of his motivation. Allergan and Medicis say that Dr. Klein is acting on his own.
The attack on ArteFill is a challenge for Artes, San Diego, Calif., which raised about $28 million in a public offering in December and is struggling to get ArteFill off the ground. In March, Artes submitted favorable data to the FDA on a five-year follow-up study of 145 patients who were treated with an earlier version of the product.
ArteFill consists of microscopic plastic particles suspended in calf collagen. The collagen is absorbed by the body and then replaced by the patient's own collagen, Ms. Goostree says. The polymer beads are permanent. Ms. Goostree says similar polymers are used in other implanted medical devices, including bone cement and pacemaker covers.
The technology was invented by a German physician, Gottfried Lemperle, who co-founded Artes in 1999 with his sons, Stefan and Martin. Earlier versions of ArteFill, called Arteplast and Artecoll, have been sold by other companies for years in Europe and Canada. In 2001, the Swiss Federal Health Agency advised physicians against the use of any "non-resorbable filling material" for treatment of wrinkles, though it wasn't an outright ban.
In a Securities and Exchange Commission filing for its stock sale last year, Artes disclosed that Dr. Gottfried Lemperle illegally injected nine people in the U.S. before ArteFill was approved for marketing. The FDA, the filing said, confirmed to the company that it had opened a criminal investigation of the matter. A product-liability and fraud suit filed against the company and Gottfried and Stefan Lemperle, among others, was withdrawn after the FDA probe came to light, but an attorney for a patient who claims she was disfigured says he expects to refile it later. Artes says the Lemperles are no longer affiliated with the company, except as stockholders. Gottfried Lemperle's attorney, Megan Richmond, San Diego, Calif., declined to comment. Neither Stefan Lemperle or his attorney could be reached.
The FDA tests were conducted with Artecoll, and when they were finished, the agency said Artes would have to agree to some changes to gain approval: refinements to the process of making the beads, that the collagen be harvested from a tightly monitored herd in the U.S. and that the product be manufactured in an FDA-approved facility. After meeting those requirements, Artes changed the name to ArteFill.
Artes says it has so far trained about 600 doctors in the injection technique for ArteFill. Tina Alster, a Washington dermatologist, says her patients haven't had any problems with ArteFill. She says that patients who have spent "oodles" of money over the years are asking for something longer lasting. She charges about $1,800 per syringe of ArteFill, or more than double the $800 price for the first syringe of a temporary filler like Restylane.
Ms. Goostree says that when she met with Dr. Klein he wasn't aware of the data from the five-year study on the Artecoll patients and didn't understand the refinements that had been done at the FDA's request. Dr. Klein says the product's name keeps changing, but there's no evidence that it is improving because the new product was not the one tested. He and other critics also say the original Artes study was too small to yield reliable results and the follow-up study tracked only about 60% of the 234 patients treated with the product. Ms. Goostree says that is "a very, very good percentage."
A New York plastic surgeon who signed the letter, Daniel C. Baker, says he has seen half a dozen patients who had Artecoll injections in other countries "with significant deformities." Last month, "I did a pretty extensive operation to remove it" from the lips and smile lines of a woman injected in Paris, he says. Dr. Baker says he hasn't reviewed Artes's data, and adds that he has "no commercial interests or affiliations and I never have." Ms. Goostree says it was "quite likely" that the physician who had administered the shot hadn't been properly trained.
Another signer, San Francisco dermatologist Richard Glogau, says his primary goal is to persuade the FDA to overhaul its review process for cosmetic injectables, including requiring studies of what happens to human tissue when products like ArteFill are injected. Dr. Glogau consults for Allergan and Medicis, among other companies, but says those relationships don't sway his professional judgment. Dermatology.
