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Here’s an interesting and provocative story. Please note that one point I made to this reporter (not entirely represented in the final piece) was that RMPs play a very important role — but that they must be joined by other more innovative and inclusive programs.
Gottlieb Speech Signals a Sea Change in FDA Drug Safety Strategy, Advocate Says
Drug Industry Daily, June 19, 2006
A senior FDA official’s speech urging the agency to pull back from requiring risk management plans as a part of the drug approval process signals a major change in the FDA’s thinking on drug safety, an industry observer says.
Scott Gottlieb, the agency’s deputy commissioner for medical and scientific affairs, announced in a June 12 speech before the American Medical Association that risk management plans (RMPs), while important in some instances, may be too prevalent. As the requirement for RMPs becomes more pervasive, the burdens could become too much for physicians and their patients, he added. “I worry about the future,” Gottlieb said.
Instead, the agency should look to a more collaborative approach, placing more responsibility on the medical community’s shoulders to ensure that medicines are used correctly, Gottlieb said.
“I believe some of the same safety goals embodied in the RMPs could be achieved if we had more ability to collaborate more closely and effectively with physician organizations,” he added.
This announcement shows that the agency has realized that there is a better way to enhance drug safety than requiring RMPs, Peter Pitts, director of the Center for Medicine in the Public Interest and a former FDA associate commissioner for external relations, told DID. This speech is a “very clear signal to people within the agency” that a change is necessary, he added. Drug safety “cannot be viewed as a punitive measure.”
Up to now the agency has used RMPs to show that they are doing something about drug safety, but these plans are an empty measure of success, he said. Gottlieb’s speech shows the agency is ready to stop “hiding behind” RMPs and take a better approach, Pitts added. Because doctors have the final say over their patients’ use of drugs, they must be more involved in the drug safety process. It is “crucial” for the collaboration that Gottlieb spoke about to take place, he said.
This speech may have been timed to coincide with ongoing Prescription Drug User Fee Act (PDUFA) negotiations and a growing call in Congress for a new FDA office to handle drug safety, Pitts said.
PDUFA is a vehicle for the agency to receive much of its funding, but that funding is tied to the FDA meeting specific performance goals. The speech may be a signal to Congress that the amount of RMPs the agency requires should not be used as a performance measure, Pitts said.
RMP meetings between the FDA and industry are considered part of the current PDUFA process. Congress must reauthorize PDUFA by Oct. 1, 2007.
The agency may also be using this concern about RMPs to head off lawmakers’ efforts to establish a new FDA drug safety office, by arguing that more collaboration, rather than further prescriptive approaches, is the right way
to go to increase safety, Pitts added.
But another industry source does not believe Gottlieb’s comments necessarily represent a new agency position. Gottlieb discussed many topics during the speech, including a balanced view about the importance and drawbacks of RMPs, Sara Radcliffe, the Biotechnology Industry Organization’s managing director of science and regulatory affairs said. Arguing that the portion of Gottlieb’s speech where he states his concerns with RMPs represents a change in the FDA’s view may be “reading too much into it,” she added.
The AP headline reads:
“Number of seniors with drug coverage down”
Here’s the first paragraph:
WASHINGTON (AP): About 500,000 fewer Medicare beneficiaries have prescription drug coverage than the federal government originally projected this month.
But here’s the story:
The drop occurred because many of the 3 million beneficiaries being counted as getting coverage through the Veterans Affairs Department had switched over to a private plan under Medicare Part D, so they were being counted twice, said Mark McClellan, administrator for the Centers for Medicare and Medicaid Services.
So, in fact, the number of seniors with drug coverage is NOT down.
But, as usual, Mark McClellan — the hardest working man in health care — puts the story in the proper perspective:
McClellan said the new numbers reflect that the Medicare program was more popular with veterans than had been anticipated. When VA officials ran final numbers after the May 15 enrollment deadline, they found that about a third of those seniors participating in VA drug coverage had enrolled in a private plan under Medicare Part D.
And, at the end of the day, according to the story:
… the new numbers do little to change the overall percentage of seniors with some insurance coverage for their medicine. About 90 percent have some coverage, either through Medicare or through another program, officials say.
Talk about Headline News!
Scott Gottlieb doesn’t just talk the talk..this is a guy who cares about patients and knows that physician discretion is still a primary source of medical innovation. And he knows that real risk management comes with integrating advanced technologies early in the drug development process, not burdening doctors and patients with paperwork as with the Tysabri risk management program…Read the article below as a great example of how Scott and FDA staffers are making a difference and why they deserve more time, money and resources to innovate:
FDA Official Questions Key Drug Safety Policy - 16 June 2006 Drug Industry Daily - By Stephen Langel
The FDA is growing increasingly concerned about its own practice of requiring companies to provide risk management plans (RMPs) as a condition of drug approvals, a high-ranking agency official said.
The FDA believes that RMPs, while important in some instances, may be too prevalent, Scott Gottlieb, the agency’s deputy commissioner for medical and scientific affairs, said in a speech before the American Medical Association. As the requirement for RMPs becomes more pervasive, the burdens could become too much for physicians and their patients, he said during the June 12 speech. “I worry about the future,” he said.
An RMP is a method the agency uses to assess the risks and benefits of a drug and minimize the risks while maximizing the benefits. But Gottlieb believes these plans — which many times include physician training programs for proper use of the drug, public notices about its dangers and drug registration programs could become too much of a burden and restrict doctors’ discretion.
“The more we promulgate plans that attempt to guide or even control [medical] decisions, the more we encroach on professional autonomy,” he said. This is especially problematic when busy clinics do not have the time to go through the various steps these plans require, he added.
Industry groups such as PhRMA have also expressed concerns with the burden RMPs can represent. The group has argued that while it supported the idea of RMPs, the agency needs to ensure that they do not impose overwhelming burdens on the medical community. “Care must be taken not to overburden the healthcare system by using too many resource-intensive tools in RMPs,” the group said in a risk management presentation.
Both the FDA and the medical community are to blame for this trend, Gottlieb told DID in a follow-up interview. While doctors have not always done everything possible to police themselves, the agency has not always created opportunities for physicians to be involved in ensuring safe drug use, he said.
The agency believes that greater cooperation between the FDA and the medical community is the solution. “I believe some of the same safety goals embodied in the RMPs could be achieved if we had more ability to collaborate more closely and effectively with physician organizations,” he added.
To reach this goal the agency is working to establish an office that will ensure more regular collaboration and communication about clinical issues with medical organizations, Gottlieb said. Terry Toigo, the agency’s acting associate commissioner for external relations is heading the team that is developing this new office, he added.
Gottlieb raised his concerns at a time when the agency has made RMPs a common requirement in granting drug approvals. For example, the FDA recently allowed multiple sclerosis drug Tysabri to be sold after the product was pulled from the market, but only if the company provided an RMP (DID, June 6).
Not really. When’s the last time you saw any pol manufacture or expend any political capital to advocate for faster cures.
By the way, on the Ketek matter. How many articles have mentioned that nearly ten million prescriptions have been written for Ketek worldwide since it was approved in Europe in 2001 and about 5 million have been written in the US since it was approved here in 2004. Over that time there have been 11 cases of acute liver failure, including the four deaths, in patients treated with Ketek, according to an FDA memo. FDA safety evaluators also uncovered 23 other cases where patients suffered serious liver injuries after receiving the antibiotic. Which means the incidence for liver problems (we can assume a part of those were the result of genetic mutations and poor prescribing, neither of which can be anticipated under our current regulatory system) is about .00066 percent and a death rate of 0.0000008
Meanwhile, “Acetaminophen poisoning has become the most common cause of acute liver failure in the United States,” report the authors of a new study in the December 2005 issue of Hepatology, the official journal of the American Association for the Study of Liver Diseases (AASLD). While attempted suicides still account for many cases, almost half are the result of unintentional overdose.
Now about 100 million people use acetaminophen each year. And each year about there about 56,000 ER visits and 100 deaths (liver failure) attributed to the drug. That’s an injury rate of .000056 if my math is right and a death rate of 0.0000001. This drug has the same genetic problems with metabolism as Ketek.
Meanwhile the community acquired pneumonia for which Ketek was developed and is used for — since other antibiotics are failed to beat back resistant bacter — leads to 500,000 hospitalizations and 50,000 deaths a year.
Somehow Grassley and the media has misplaced these facts, along with the incontrovertible evidence that the drug works.
The U.S. Food and Drug Administration has approved a combination of Hycamtin (topotecan hydrochloride) and cisplatin for use as the first drug treatment for women with late-stage cancer of the cervix when a physician determines that surgery or radiation therapy are unlikely to be effective. The approval includes a new indication for Hycamtin, which was approved in 1996 for treating ovarian cancer and in 1998 for small cell lung cancer.
In the United States there are an estimated 10,000 new cases of cervical cancer and about 3,700 related deaths each year.
“We are making great strides in the fight against cervical cancer, a disease that, world wide, is the second most common cancer in women,” said Dr. Andrew von Eschenbach, Acting FDA Commissioner. “This course of drug therapy is a potentially life-prolonging option for thousands of women.”
No doubt a Congressional hearing will be called to investigate.
Has Charles Grassley finally jumped the shark in his attempt to generate media attention with his fearmongering over drug safety? His marching over to the HHS to demand a meeting with the official who is “covering up” the coverup of the coverup of Ketek fizzled when the sober-minded folks there simply told him to get lost.
Here is the breathless account from the Washington Post:
“After months of trying to get firsthand information from a government official familiar with a controversial new antibiotic, Sen. Charles Grassley, R-Iowa, marched into the Department of Health and Human Services headquarters Wednesday asserting his congressional right to receive the data.
After a brief meeting with senior HHS and Food and Drug Administration officials, Grassley departed empty-handed and angry.
“This is extraordinary for me,” the senior Republican said outside the headquarters. “I haven’t had to go to an agency like this since 1983 to get information I requested.”
“I smell a coverup,” he said.
Even Post reporters have to put some fact outs…..turns out Grassley does have his hands full….
“FDA officials denied any impropriety, saying they were cooperating with Grassleyé¾ staff and had sent 400 boxes of documents related to the approval and safety of the drug, Ketek. Some information had to be withheld, the agency said, because of continuing investigations.”
So much for Grassley’s effort to turn the Ketek incident, which in no way affected the safety or the importance of the drug, into the DaVinci Code.
What’s more the FDA is planning to go head and submit the data to an FDA advisory committee for an application to use Ketek for another infection…. I think Grassley’s act is wearing thin and prancing over to HHS to exercise his congressional right (does that include the right to yank FDA staffers away from their job and have them work in your office to dig up dirt on the agency they are supposed to work for, Senator?) only to be told to keep his pants on is pretty damn funny. Hey Chuck, any limos driven by guys wearing black following you as well?
We need more of this resolve on the part of the FDA and companies. That’s how you treat blowhards and bullies who think they are Jack Bauer but instead wind up looking like Inspector Clousseau.
One of the most difficult meetings I ever held at the FDA was with a group of parents (mostly moms) of teenagers who had committed suicide while taking SSRI antidepressants. In the wake of a very emotional advisory committee meeting, heavily covered by the media, these well-meaning and understandably devastated parents believed that these medicines were the cause of their horrible losses. I listened. Afterwards I wept. A parent of two children, I cannot even begin to understand their agony.
But as much as they needed to believe that the medications were at fault, the science was never clear. Anecdotal events, even terrible ones, are not science. Now a major new study, the first of its kind, finds that rather than boosting suicide rates, SSRIs have actually saved thousands of lives by preventing suicides since they were introduced in 1988.
And before you ask, no, the study was not funded by a pharmaceutical company. The funding came from the NIH and the Dana Foundation. The full study appears in the June issue of the journal PLos Medicine.
For this study, the authors analyzed federal data on suicide rates since 1960, along with sales of fluoxetine (Prozac) since it became available in 1988. Analysis was continued through 2002. Prozac was used as a benchmark for the broader class of drugs.
Between the early 1960s and 1988, suicide rates held relatively steady, fluctuating between 12.2 per 100,000 and 13.7 per 100,000.
Since 1988, however, suicide rates have been on a gradual decline, with the lowest point being 10.4 per 100,000 in 2000. During the same time frame, Prozac prescriptions rose, from 2,469,000 in 1988 to 33,320,000 in 2002.
Using mathematical modeling, the investigators estimated the rates of suicide if the pre-1988 trends had continued, estimating that there would have been an additional 33,600 suicides if the pre-1988 trends had been maintained.
With that in mind, moves to restrict the use of SSRI antidepressantscould have a harmful effect, the authors stated.
“I don’t think these claims that antidepressants increase suicide have a solid base,” said Dr. Julio Licinio, lead author of the study and Chairman of the Department of Psychiatry and Behavioral Sciences at the University of Miami.
“If you have a drug that’s supposed to be causing something, the more of the drug that’s used, the more of the bad outcome you would have. What we show is the converse.”
Whille this new science will provide little solice to the parents I met, it will help mental health professionals, their patients — and their patients’ loved ones — better understand the value of available therapies.
And that’s important. Very.
There was no — none, zero talk of denial. Rather there was talk of trying to get straight what the enforcement procedures would be,” Crawford testified, according to a transcript of the May 24 deposition that was released late Monday by the Center for Reproductive Rights Ã¢ which has sued to force the FDA to allow over-the-counter sales of Plan B for all ages.
So, there was no conspiracy to deny young women access to OTC sales of Plan B? What this depostion reveals is that Dr. Crawford was willing to make a tough decision and exercise leadership. He knew the political consequences of the perception of his actions and didn’t care. He is more of a mensch than the those who attacked him ever will be. Maybe all the media speculation and second -guessing about Dr. Crawford’s integrity and motivation will stop. Maybe all the hit and run attacks on the FDA fed to reporters by Sid Wolfe and his ilk will stop and we can actually have a rational discussion of how to make drug development faster and safer. Too much to hope for perhaps.
We can’t all have our own personal FDA. Not you. Not me. Not Senator Charles “I’m not a doctor but I play one on C-SPAN” Grassley, not Consumer Reports.
Consider Consumer Reports. Based on its “own” analysis of FDA data, it reached a significantly different conclusion than all of the scientists and food experts at the FDA’s Center for Food Safety and Applied Nutrition (CFSAN). Despite the fact that both the FDA and the EPA said that pregnant women should eat more fish — including tuna fish — Consumer Reports says the opposite. All the best science supports the FDA. All the lawyers support Consumer Reports. And who do you think gets the media coverage?
And as Senator Grassley moseys over to the Department of Health and Human Services today for another session of media-savvy grandstanding, we would all do well to remember the words of Dr. Mark Goldberger, director of FDA’s office of antimicrobial products:
“It’s more complex than it seems at first glance.”
This just in off the AP wire …
An experimental vaccine is showing promise against Alzheimer’s disease, reducing brain deposits that are blamed for the disorder.
The deposits have been cut by between 15.5 percent and 38.5 percent in mice, with no major side effects, researchers said Monday in the online edition of Proceedings of the National Academy of Sciences.
Tests of the DNA-based vaccine are under way in monkeys, and if those are successful, testing in people could begin, perhaps within three years, said lead researcher Yoh Matsumoto of the Tokyo Metropolitan Institute for Neuroscience in Japan.
If all goes well, this type of treatment might be available for people in six or seven years, he said.
Scientists estimate that as many as 4.5 million Americans suffer from Alzheimer’s, the most common form of dementia. The illness, named after Dr. Alois Alzheimer, a German doctor who studied it in 1906, involves the parts of the brain that control thought, memory and language.
Its cause remains unknown, and while there is no cure some drugs can slow progress of the illness in people in the early and middle stages.
Other efforts to develop an Alzheimer’s therapy also are under way.
Two years ago, trials of a potential vaccine that seemed to help slow the memory decline caused by the disease were halted after several participants developed brain swelling.
Matsumoto said that problem did not occur in the tests of his vaccine.
The brains of people suffering from Alzheimer’s disease are cluttered with a plaque made up of a small protein called amyloid beta, or Ab.
In the mouse tests, the Ab deposits were reduced overall, and in certain parts of the brain the reduction was as much as 50 percent, the researchers said.
Dr. Sid Gilman, a professor of neurology at the University of Michigan who has done research in vaccines for Alzheimer’s, said the new research showed the vaccine was efficient and safe in the mice.
He cautioned, however, that it’s very difficult to compare the level of efficiency from one trial to another, “so how effective this may be compared to other approaches is debatable.”
The reasons for the brain swelling in the earlier tests have been determined, Gilman said, and new forms of that therapy are now being tested.
A variety of clinical trials are under way looking at other potential treatments for Alzheimer’s including a hormone that might prevent brain cell death, several drugs, antioxidants, cholesterol-lowering medications and antibodies.
The Japanese research was funded by the ministry of education of Japan and the Novartis Institute of Biomedical Research.