Dr. Daniel Schultz, who has been FDA’s chief medical device official, is the first high ranking FDA official whose controversial device approvals have resulted in his leaving the agency "by mutual consent."
Earlier this year, nine scientists spoke up to incoming President Obama that they had concerns about how medical devices were approved without adequate checks for effectiveness and safety. Read more:
The approvals had been issued by Dr. Schultz, over the objections of FDA scientists.
Dr. Janet Woodcock, director of the FDA’s all-powerful, Center for Drug Evaluation and Research (CDER), is under investigation by the Inspector General.
The investigation was commenced after an ethics complaint was filed by Amphastar Pharmaceuticals Inc. which charges that Dr. Woodcock has a conflict of interest favoring its competitor, Momenta Pharmaceuticals Inc.
Both companies seek approval for the generic version of the drug, Lovenox, a blood thinner with multi-billion-dollar sales.
The Wall Street Journal reports (below) that Dr. Woodcock’ close contacts with Momenta in the middle of a drug-approval process were (to say the least) ethically questionable. Morgan Stanley characterized the Woodcock / Momenta connection as a "game changer" whereupon Momenta’s stock jumped 17% in a day.
It is further reported that Dr. Woodcock co-authored journal articles with Momenta scientists, then co-authored two medical journal articles last year that won scientific — as well as Wall Street — kudos for Momenta.
The WSJ notes: "It is unusual for FDA officials to co-author journal articles with industry researchers, though the FDA said it encourages publication in journals in collaboration with noted scientists. Dr. Woodcock, who joined the FDA about 20 years ago, has done so only a handful of times in recent years. In addition, this instance occurred in the middle of a drug-approval process."
Another high ranking FDA official, Dr. Thomas Laughren, FDA’s director of psychiatry products, overruled FDA’s team of safety officers, much as Dr. Schultz did:
On April 29, 2007, Dr. Laughren issued an approvable letter to Eli Lilly for pediatric use of Zyprexa (olanzapine) – despite serious concerns about the integrity of the data obtained in Russia.
Dr. Thomas Laughren has been in a pivotal high ranking position at FDA’s powerful CDER center that has authority over the review and drug approval process since 1983.
Throughout his tenure at the FDA Dr. Laughren has maintained close ongoing collaborative ties with pharmaceutical industry officials and industry financed psychiatrists in academia and professional associations.
Dr. Laughren has participated in influential industry sponsored consensus panels convened by the American Academy of Child and Adolescent Psychiatry (AACAP) that recommended expanded use of psychotropic drugs-primarily SSRI antidepressants and the so-called ‘atypical’ antipsychotics-for unapproved, off-label uses in children.
The Alliance for Human Research Protection has compiled a list of influential journal articles, a book chapter, and industry sponsored consensus statements that list Dr. Laughren as co-author–thereby greatly enhancing their influence.
Dr. Laughren participated in consensus forums whose purpose was to influence regulatory policy and /or expanded use of psychotropic drugs and to influence practice guidelines. His name and position are penned to articles whose authors include Eli Lilly’s chief medical officer, and unabashed industry-subsidized drug promoters -even a convicted felon.
For more than a decade Dr. Laughren endorsed industry’s denials that SSRI antidepressants increased the suicide risk for consumers. He dismissed safety concerns raised by FDA medical reviewers: instead, he penned his name to articles and consensus statements that recommended broadening the criteria for diagnosing psychiatric illness and expanded use of SSRI antidepressants, antipsychotics, and combinations.
For example, Dr. Laughren’s name is penned to consensus statements recommending broadening the criteria for pediatric bipolar disorder. Such an endorsement by Dr. Laughren provides an authoritative green light to physicians to prescribe antipsychotics–the most hazardous drugs in pharmacopoeia for children–even as the drugs had not been approved for children.
Dr. Laughren not only co-authored major articles promoting industry’s marketing goals but his name is penned to an apparently ghostwritten article:
"Mood Disorders in the Medically Ill: Scientific Review and Recommendations," published by the Journal of the Society of Biological Psychiatry, 2005.
The article promotes the notion that depression accompanies practically all patients with medical illnesses-e.g., cardiovascular disease, cancer, AIDS, Alzheimer’s, Parkinson’s, Diabetes, Osteoporosis, Obesity, and Pain. Dr. Laughren, a co-author, recommends the use of antidepressants for presumed underlying depression, even claiming that "SSRIs may be cardioprotective."
Dr. Laughren’s name has lent the appearance of legitimacy of what is clearly industry propaganda that has no basis in science or evidence-based medicine.
See, AHRP letter of complaint addressed to the former FDA commissioner, Dr. Andrew vonEschenbach (June 2007)
and a follow-up letter (April 2008) at: https://ahrp.org/cms/images/stories/articles/fda-double-agent2008.pdf
Dr. Schultz, Dr. Woodcock, and Dr. Laughren are among top echelon FDA officials who have held sway for years, serving the interest of the industry they are supposed to regulate. These pivotal FDA officials–and several others–have approved unsafe–indeed, dangerous–prescription drugs and medical devices disregarding the recommendations of the agency’s safety scientists.
The beneficiaries of ill-considered FDA marketing approvals have been drug and device manufacturers, while the American public has been badly served: millions have suffered serious harm, hundreds of thousands have died as a result of poorly reviewed FDA-licensed drugs and devices.
See: QuarterWatch analysis of FDA adverse event reports for the third quarter of 2008–bear in mind that adverse events reported to the FDA comprise only between 1% and 10%:
"During the third quarter of 2008 the FDA received 24,872 serious adverse drug event reports identifying 854 different drugs.
For the third quarter of 2008 reported serious, disabling adverse drug events were 30.5% higher than the same quarter one year ago.
There were 2,778 patient deaths, 1,162 cases of disability and 20,932 cases of other kinds of serious injury.
Reported patient deaths in the third quarter were 41% higher than the same quarter in the previous year.
See, synopsis of this QW report at: https://ahrp.org/cms/content/view/588/9/
Posted by Vera Hassner Sharav
The Wall Street Journal
AUGUST 12, 2009, 5:06 A.M. ET
FDA Medical-Device Regulator Resigns
By ALICIA MUNDY
WASHINGTON — The Food and Drug Administration’s top medical-device regulator said Tuesday he is resigning.
The departure follows internal dissent over device-approval decisions that the regulator’s critics said were too friendly to industry.
Daniel Schultz said his move comes "by mutual agreement" with FDA Commissioner Margaret Hamburg, who took office in May.
An FDA spokesman said Dr. Schultz’s decision came as the result of talks with Dr. Hamburg, and had nothing to do with any specific issue related to a device’s approval process.
Dr. Schultz has worked at the FDA’s Center for Devices and Radiological Health for 15 years and led it for the past five years.
Sen. Chuck Grassley (R., Iowa) held hearings two years ago on Dr. Schultz’s approval of a nerve stimulation device to treat depression, approval that came over the objections of several FDA doctors. Mr. Grassley complained at the time that science was being ignored in favor of industry. Dr. Schultz said his decision was based on sound medical data.
In March, Sen. Grassley opened an investigation into a knee-surgery device made by ReGen Biologics Inc., after The Wall Street Journal reported that Dr. Schultz approved it over the objections of numerous FDA scientists and reviewers.
FDA Deputy Commissioner Joshua Sharfstein said in May that the agency would re-examine the approval process for the ReGen knee device to see if proper procedures were followed.
A group of nine device division employees wrote to the House Energy and Commerce Committee last October to complain that the division’s leaders had approved devices despite formal safety and efficacy concerns raised by FDA.
They also alleged some scientists who objected to the decisions faced retaliation from leaders of the device division. The FDA at the time declined to comment.
The Advanced Medical Technology Association, a medical-device industry group, praised Dr. Schultz, saying he ensured stable funding for the FDA via industry user fees.
Dr. Hamburg said in a statement that Dr. Schultz left a strong legacy and helped the division enhance understanding of medical-device use in children.
Write to Alicia Mundy at email@example.com Printed in The Wall Street Journal, page B2 ~~~~~~~~~~~~~~~~~~~~~~~~~
The Wall Street Journal
AUGUST 12, 2009
Drug Chief at the FDA Is Accused Of Conflict
By ALICIA MUNDY
WASHINGTON — The inspector general of the Department of Health and Human Services is investigating a conflict-of-interest allegation involving the official in charge of drug approvals at the Food and Drug Administration, the FDA said.
The investigation of Janet Woodcock, the director of the FDA’s Center for Drug Evaluation and Research, stems from an ethics complaint filed by Amphastar Pharmaceuticals Inc., a California company that says it has been delayed in its six-year effort to win approval for a generic version of Lovenox, a multi-billion-dollar blood thinner.
In its complaint, Amphastar alleges that its competitor had special access to Dr. Woodcock at critical times in the prolonged approval process, which is ongoing. Amphastar points out that Dr. Woodcock co-authored a scientific paper with scientists at Momenta Pharmaceuticals Inc. while both companies were battling to win FDA approval of their generic blood thinners.
Amphastar contends that Dr. Woodcock’s collaboration with Momenta is a conflict of interest and has asked that she recuse herself from the entire matter at the FDA.
"The FDA is aware of the situation, takes it seriously, and is looking into the matter," an agency spokesman said. He said Dr. Woodcock isn’t recusing herself.
The FDA, responding to repeated queries over a week, declined to make Dr.
Woodcock available for comment. An HHS official said the department cannot confirm or deny ongoing investigations.
In separate FDA news, the agency on Tuesday said its top medical-device regulator, Daniel Schultz, is resigning, following internal dissent over decisions that his critics said were too friendly to industry.
Both Amphastar and Momenta, which is based in Cambridge, Mass., submitted applications seeking FDA approval of their generic versions of Lovenox heparin sold by Sanofi-Aventis SA. Amphastar applied in 2003, two years before Momenta.
Lovenox, a low-molecular-weight heparin, is a blockbuster biologic drug that brought in $3.5 billion in world-wide sales last year.
On Nov. 2, 2007, the FDA rejected Amphastar’s application, although the agency acknowledged that Amphastar had passed a key hurdle in demonstrating its drug’s chemical equivalence to Lovenox. The FDA told Amphastar that it needed more data to show that the product wouldn’t cause dangerous immune reactions.
Momenta was also asked to submit such data. Both companies said they have complied and are awaiting the FDA’s response.
Amphastar, in letters sent to the FDA in April and June, cited some public contacts and email between Dr. Woodcock and one of Momenta’s founders, Massachusetts Institute of Technology biological engineering professor Ram Sasisekharan, beginning in February 2007. Among those contacts were their attendance at an international medical conference in Thailand in November 2007.
Mainly, however, Amphastar points to Dr. Sasisekharan’s appointment to lead an FDA task force in early 2008, which put him and Momenta in regular contact with the agency. That task force was investigating tainted Chinese-made heparin, a crisis that led to nearly 100 deaths.
Drs. Woodcock and Sasisekharan, along with other Momenta scientists, then co-authored two medical journal articles last year identifying the cause of the contaminated Chinese heparin imports, a finding that won scientific — as well as Wall Street — kudos for Momenta.
It is unusual for FDA officials to co-author journal articles with industry researchers, though the FDA said it encourages publication in journals in collaboration with noted scientists. Dr. Woodcock, who joined the FDA about 20 years ago, has done so only a handful of times in recent years. In addition, this instance occurred in the middle of a drug-approval process.
Dr. Woodcock has held her post since 1994, except for two years as deputy commissioner under George W. Bush.
In April 2008, after the tainted-heparin article was published, an investment report from Morgan Stanley cited Momenta’s FDA connection as a "game-changer," and Momenta’s stock jumped 17% in a day.
Dr. Sasisekharan didn’t respond to calls or emails seeking comment.
Momenta’s chief executive, Craig Wheeler, said contacts between representatives of his company and Dr. Woodcock were appropriate. He said they were part of an effort to persuade the FDA that it should use a higher standard of equivalence in approving generic versions of Lovenox — a standard that he believes Momenta’s technology enables it to meet.
"I’m not sure why having lower [generic] standards would be in the public interest," said Mr. Wheeler.
He noted that the FDA’s demand for more information about immune reactions affected Momenta as well as Amphastar, and caused Momenta’s share price to fall nearly 60% on Nov. 6, 2007.
Without addressing the specific case, an FDA spokesman cited "evolving science" as having raised agency concerns about immune-system issues with complex drugs such as Lovenox.
While the tainted-heparin crisis offered rival Momenta a chance to shine, it added to the delays for Amphastar. At the height of the Chinese heparin crisis in 2008, Amphastar learned that one of its Chinese suppliers for the main ingredient used in its experimental heparin had misled the company about where the raw material had been produced, although the FDA didn’t find contamination.
The FDA sent warning letters to two Chinese suppliers of Amphastar in April this year.
Momenta has teamed up with a unit of Swiss drug giant Novartis AG to bring its product to market.
A Novartis spokeswoman said the company was unaware of the ethics complaint filed by Amphastar.
-Jake Sherman contributed to this article
Write to Alicia Mundy at firstname.lastname@example.org Printed in The Wall Street Journal, page B1
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