Latest Drugwonks' Blog
Here’s some new research that’s not surprising but enormously important —patients and doctors frequently don’t comply with some of the so-called black-box warnings on prescription drugs. This according to a Harvard Medical School study of nearly a million patients.
Researchers from Harvard and several hospitals and health plans found that compliance with the warnings varied substantially — from extremely good for certain drugs that can’t be taken during pregnancy, to poor for others that should be followed with regular diagnostic tests.
The findings, published today in the journal Pharmacoepidemiology and Drug Safety, suggest that pharmacists and regulators “need to find out how we can communicate the content of the warning clearly to clinicians and patients,” said Anita Wagner, the study’s lead author and an assistant professor in the department of ambulatory care and prevention at Harvard Medical School.
The Wall Street Journal reports that Paul J. Seligman, who oversees post-marketing drug surveillance at the FDA, says the study shows the need for more research to give doctors and patients clearer warnings. Dr. Seligman says it’s important to “develop the science for monitoring adverse events in ways that will allow us to give adequate warnings.”
Paul is a talented and dedicated career professional — but he and others at the agency must realize that before FDA can be a part of the solution, they must first stop being part of the problem. The move to more and more black box warnings as well as other warnings based on very early science is causing “warning fatigue” and it should be no wonder that both physicians and patients are taking them less seriously.
Further, it’s not only about learning how to better monitor adverse events — it’s about learning how best to communicate with doctors, pharmacists and consumers the risks associated with various medicines. And that’s as much science as art.
But first, do no harm.
When is a conflict of interest not a conflict of interest? When it serves the political whims of Senator Charles Grassley. Seems that an FDA employee was removed from an agency review of Wyeth’s heartworm drug Proheart 6 because of possible personal and financial conflicts of interest. (Wyeth voluntarily pulled Proheart 6 from the U.S. market in September 2004, after thousands of reports of serious side effects, and the death of 600 dogs.) According to a Reuters report, the FDA launched a criminal investigation of the employee but took no action. The employee went to visit Senator Charles Grassley, the new father-confessor of disgruntled FDA employees. The result, another outbreak of Mad Corn Disease on the floor of the United States Senate. This dog won’t hunt.
The following from Dr. Bob Goldberg — the real public citizen …
Merrill Goozner is a one of the many haters of medical progress at the Nader organization Public Citizen. Nader is the man who hates drug prices but loves to profit from drug companies by investing in their stocks, but that’s another matter. He has his own blog with the Seussian name of Gooznews.com. Goozner never misses an opportunity to apply a careful misreading of medical journals and pharmaceutical statistics to make the case the most drugs are worthless and that the rest that aren’t were developed largely by government researchers. He most recent assault on an article in JAMA reporting on the results of the Incremental Decrease in End Points Through Aggressive Lipid Lowering Study Group (IDEAL) is a case in point. Actually if he had read the full title of the study perhaps he wouldn’t have wasted his copious brainpower attacking the research. The study was designed to determine is substantial reductions in cholesterol levels could be achieved and if so, could they incrementally reduce death due to heart attacks, non-fatal heart attacks or cardiac arrest with resuscitation for people that already had one heart attack. The study had an interesting wrinkle: patients knew what drug they were getting and some even entered the study taking one of the two medicines taken at the most aggressive dose for Lipitor and the normal dose for Zocor.
Turns out that whatever reduction in major events could not be associated with a reduction in cholesterol. However, there were a strong relationship between use of Lipitor and a decline in the incidence of coronary heart disease. On the downside, about 10 percent of people on Lipitor stopped using due to adverse events compared to 5 percent of Zocor patients.
That’s what the study said. And it also said that overall the benefits of additional cholesterol reduction were incrementally beneficially at best for people that have already had one heart attack. No more and no less. But Goozner tries to paint the study as a cover-up of more people dying from heart attacks on Lipitor than Zocor (4 patients). Actually, the data is there on table three of the study. And he screams that there is no discussion of greater incidence of adverse events associated with Lipitor. Again untrue. It’s on page 2443 of the article. (JAMA Nov. 16, 2005 Vol 294, No 19)
Maybe Goozner, who in the past has trashed targeted cancer drugs as worthless or too expense, should read more carefully. Or less selectively. Or with greater intellectually honesty. Or with more intelligence. Or all of the above.
Here is the lead the “mainstream” media is running about the GAO report on Plan B:
“Food and Drug Administration officials, months before a scientific review was completed, had already decided to reject over-the-counter sales of the emergency contraceptive pill, also known as Plan B.”
What the GAO actually reported is much less sexy. The GAO interviewed some FDA staffers who claimed they were told that a decision had been made in advance of the evidence. The GAO also reports that top FDA officials firmly deny this accusation — a inconvenient fact that it omitted from most news reports.
As my grandmother used to say, a half-truth is a whole lie.
According to the new FDA White Paper on PDUFA, more and more companies are seeking early advice from agency. FDA’s research has shown that this increased communication results in a more informed and efficient drug development process for industry sponsors. Since 1999, requests for meetings to discuss products stalled in development have increased more than 200 percent. Requests for consultations to review clinical milestones and next steps in the development process are up more than 60 percent. In the past two years, the number of industry-requested meetings scheduled between FDA and industry sponsors has almost doubled, from 1642 meetings in 2002 to 2132 meetings in 2004. With more frequent FDA guidance and consultation, the quality of new product applications has improved, and fewer review cycles are needed. Before PDUFA, an average of two review cycles was needed to gain FDA approval for an NDA. In 2004, thus far the majority of NDAs have been approved after just over one review cycle.
Those who think the FDA should view the pharmaceutical industry as the enemy misunderstand (and at great peril) a crucial 21st century regulatory paradigm — collaboration advances the public health. As James Thurber said, “It is better to know some of the questions than all of the answers.”
And they’re off.
The good news is that one of the world’s largest pharmaceutical wholesalers (McKesson) is tightening up its supply chain. The bad news is that they weren’t going to make it public. The story became public when McKesson’s letter to Kevin Fagin — whose son received injections of a counterfeit anemia drug — did the right thing and made it public. (I recently testified with Mr. Fagin in front of the Government Reform Committee about the growing problem of coutnerfeit prescription drugs.)
The letter, from Ivan D. Meyerson, the general counsel, said that “on a going forward basis, [drugs] will only be purchased directly from the manufacturer or from the manufacturer’s designated sole distributor.” The letter states that the company has “no current intention of announcing this policy to the public.” The new policy means that the three top wholesalers that account for a total of more than 90% of medicines distributed in the U.S. have taken steps to cut off purchases from so-called secondary wholesalers. Such suppliers don’t purchase products directly from drug makers and create an opening for illicit knock-offs to enter mainstream channels. In the last year, Cardinal Health Inc. of Dublin, Ohio, and AmerisourceBergen Corp. of Chesterbrook, Pa., announced they would end purchases from the secondary market.
Mr. Fagin isn’t a policy wonk or an elected official or a pharmaceutical industry lobbyist. He’s a good man with a lot of courage. Thank you Kevin.
As sure as Christmas music in the mall signifies the coming of the holidays, so too do silly lawsuits and testosterone-laden accusations signal the budding of the nascent 2006 political campaign season. As the giant spruce goes up in Rockefeller Center, Montgomery County (MD) Executive Douglas M. Duncan announced that the county will sue the Food and Drug Administration to force it to allow county employees to import drugs from other countries.
It’s beginning to smell a lot like — well, it’s just beginning to smell.
According to The Washington Post, the county’s lawsuit “faces long odds.” In late September, a federal judge threw out a similar action brought by Vermont. On Nov. 2, that state’s attorney general decided not to appeal. But, hey, what’s precedent when you’ve got propaganda? “I am disappointed, but not surprised, that the Bush Administration would deny hard working people access to cheaper prescription medications,” Duncan said in a statement.
Mr. Duncan, it seems, is so worked up about the issue that he forgot to sign the legislation. He said that he’ll let the law go into effect without his signature — but will not implement the measure without FDA support. Now is that commitment or what!
Council President Tom Perez, the architect of the council’s bill, angrily accused Duncan of trying to derail the effort. “I am really reaching a point where people will lead, follow or get out of way. I will implement it out of my own office if I have to,” said Perez, who is hoping to use the prescription drug issue if he runs for state attorney general next year.
And that, dear reader, says it all.
According to the British Medical Journal, the National Institute for Health and Clinical Excellence (NICE) has developed a more rapid process for assessment that will be used initially for lifesaving medicines, including several cancer drugs.
The new “single technology appraisal” process will enable NICE to develop guidance on drugs selected for rapid assessment within eight weeks — much more quickly than the current average of 18 months. It will initially be applied to lifesaving drugs that have already been licensed and to new lifesaving medicines close to the time that they first become available.
That’s the good news.
The new appraisal process will initially be applied to 14 drugs — 13 of which are cancer drugs — that have already been referred to NICE. These include docetaxel (Taxotere) for breast cancer; paclitaxel (Taxol) for breast cancer; rituximab (MabThera) for non-Hodgkin’s lymphoma; trastuzumab (Herceptin) for breast cancer; and bortezomib (Velcade) for multiple myeloma.
That’s the bad news — that these treatments are still not cleared for use in England.
As Joanne Rule, chief executive of the cancer information charity CancerBACUP, said, “These proposals represent a bold reform package for the future, but they don’t solve the problem of the backlog of new cancer treatments currently held up at NICE.” She added, “NICE should issue interim guidance on cancer treatments already approved for use in Scotland, and it’s crucial that the government make it crystal clear that doctors can prescribe licensed cancer drugs now.”
NICE guys must finish first.
According to a new GAO report to Congress, Americans import a “substantial and increasing” number of illegal prescription drugs, but efforts to stop the sales remain scattershot. Estimates given to Congress range from 2 million to 20 million packages a year. The “very limited” information prevents regulators from directing resources efficiently to prevent shipments of addictive substances or other medications that could be harmful, the report says.
The GAO study was begun at the request of Senator Norm Coleman (R, MN.), chairman of the Senate Permanent Subcommittee on Investigations, and Representative John D. Dingell (D, MI). Here’s what Mr. Dingell had to say, “While rogue websites continue to send their drugs into the U.S. with impunity, the agencies most responsible for stopping this chaos are completely out of ideas.”
I suppose that members of Congress (such as Rahm Emanuel, Dan Burton, Joanne Emerson, Byron Dorgan and Gil Gutnecht), governors (such as Tim Pawlenty, Rod Blagojevich and Jim Doyle), hack local politicians (like Tom Perez of Montgomery County, MD and David Catania of the DC City Council), and organizations (such as Families USA and the AARP) trumpeting the mantra of drug importation has nothing at all to do with the problem. Add to that zero additional budget dollars from Congress to deal with the problem and any surprise or righteous indignation is, well, just specious.
Folks, you’re either part of the solution or part of the problem.