Latest Drugwonks' Blog
2006 began with a burst of sanity from the Washington Post editorial page which concluded its January 2nd editorial with the following statement, “Scientific judgments about the risks and advantages of drugs are not black and white — which is why they are best made by scientists and by the regulatory agency that employs them, not by jurors through the lens of hindsight.”
In medias res!
An important perspective …
Mere Magazines
By THOMAS P. STOSSEL
December 30, 2005;
The Wall Street Journal
Recently I was working in a Zambian orphanage when a young woman with worsening shortness of breath and chest pain asked me for help. Armed only with a stethoscope, I could do nothing other than diagnose a probable lethal tuberculous infection of the heart. Without devices and drugs developed by companies, doctors are not very useful. It was therefore discouraging to return to my Boston-based medical center and witness leading medical journals sanctimoniously demonizing not only the technologies developed by drug companies but also the companies themselves.
The Journal of the American Medical Association has declared industry-sponsored research categorically untrustworthy, and, to publish it, demands that an academic researcher be an author and take responsibility for its integrity, and also that an independent academic statistician analyze its data. This and other journals rail obsessively against “financial conflicts of interest” of academic researchers working with companies and conduct inquisitions to identify every possible financial motive that might corrupt researchers’ objectivity.
The ongoing Merck situation is a case in point. The New England Journal of Medicine wants the company to correct a five-year-old paper that, they allege, inappropriately excluded three late-breaking adverse events associated with the painkiller Vioxx. The company has correctly responded that published research projects always have defined beginnings and endings, and that it reported all adverse events to the FDA. With the drug off the market and Merck mired in litigation, what problem this correction would solve is unclear. Nevertheless, a Dec. 11 New York Times editorial excoriated Merck for “manipulating a journal article” and informed doctors “that they will need to take the findings of industry-backed studies with skeptical caution.” The message in all this is clear: Medical academics are saints — devoted selflessly to patient care — and corporate people are sinners, morally blinded by greed. But having worked in academic medicine for over 35 years and consulted for companies, this Manichean duality is inconsistent with my experience and a woeful distortion of reality.
In a Sept. 8 article in the New England Journal of Medicine, I reported that no systematic evidence exists that corporate sponsorship of academic research contributes to misconduct, bias, public mistrust or poor research quality. On the other hand, many academic colleagues working in my field of basic biological research (I study how your body cells crawl around, which has no obvious commercial value) would run over their grandmothers to claim priority for a discovery, impose their pet theory on the field, obtain a research grant, win an award or garner a promotion. It’s the same in other scientific fields, and no wonder, because for relatively modest remuneration we compete for scarce resources and labor in obscurity to achieve small advances few understand or appreciate. We exercise our ambitions by publishing research papers in high-profile journals. The research journal revolutionized scientific communication in the 17th century. But until the scientific enterprise grew larger than the first journals could accommodate, no peer review restricted publication. Once restrictions arose, human competitiveness established a journal prestige pecking order that grew in importance as research became more prevalent and complex. The more obscure one’s research, the greater the premium on publishing it in a prestigious journal, where those who administer limited rewards might see it, and where the news media are more likely to hype it.
But unbeknownst to the media, the journals at the top got there because of herd behavior by researchers, not because they are better than lower-tier journals at vetting research quality. Here’s why: Researchers submit their best work to the top journals, which can therefore afford to maintain their prestige by rejecting, not publishing, many high quality papers. That’s brand creation — not science. Most of their editorial effort goes into deciding which submitted papers are sufficiently newsworthy. Anonymous peer review by jealous competitors has its merits, but it has a tendency to select for fashionable if relatively unoriginal and inoffensive papers. Top medical journals compete for papers describing large clinical trials reporting small effects of treatments for diseases affecting many people, although these reports often do not substantively advance scientific knowledge, and many subsequently are invalidated. And no description of medical research in a medical journal comes close to the detail level or intense scrutiny imposed by the FDA on companies’ documentation of drug or device development before approval. Space constraints for readability and cost-savings preclude journals from publishing detailed information on the order of what companies file with the FDA, and unpaid journal peer reviewers, not to mention practicing doctors, would never read it anyway. The recent Korean cloning fiasco, in which the leading science journals published blatantly fraudulent papers, wasn’t the first such incident to afflict prestige journals, and it could never happen under conditions of FDA review. Indeed, doctors should take all studies published in “prominent medical journals” with “skeptical caution.” The lower stringency of journals compared to the FDA is a good thing, because academic biomedical research would come to a screeching halt if subjected to anything even approximating FDA examination.
Scientific knowledge advances reasonably efficiently, and new technologies emerge, despite the looseness of journals. And researchers’ craving for prestige goads them to greater efforts.If reporters understood that journals are magazines, not Holy Scripture, we might not be witnessing ever more onerous regulations inhibiting interactions between academic and industry science. Prestigious biomedical journals are good for our health — provided they stick to their core business of facilitating imperfect communication between researchers. Leave drug and device monitoring to the FDA — and theology to theologians.
Mr. Stossel is American Cancer Society Professor at Harvard Medical School and co-director of the division of hematology at Brigham and Women’s Hospital.
According to an article in The Times of London by Health Editor Nigel Hawkes (“Delay Over Top Cancer Tratment for Women”, Dec. 29), there is wide disparity of access in England’s National Health Service’s (NHS) 32 cancer networks to three new medicines for breast cancer: Femara (letrozole), Aromasin (exemestane), and Arimidex (anastrozole). According to the article, research recently published in the New England Journal of Medicine argues that Femara results in 30% greater chance of avoiding a recurrence after surgery.
The medicines are available in Scotland, and some English cancer networks, but others ration or don’t offer them at all.
This is another example in a long list that shows how so-called “public” health care fails in its primary objective: eliminating disparities in access to health services.
Furthermore, English patients do not have a choice of NHS trusts or cancer networks to use: the government has established them geographically, resulting in a “postcode lottery” , as Mr. Hawkes puts it. An Englishman’s home is his castle, but it’s also an Englishwoman’s prison if it’s within the boundaries of a cancer network that doesn’t provide her with the best treatment.
Fortunately, people in the United Kingdom have the freedom to buy private health insurance to make up for shortcomings in the government’s system (a freedom the Canadian government still denies to its subjects). The major competitor in the private insurance market in the U.K. is BUPA, a non-profit outfit whose standard benefits include “access to new, effective drugs and other treatments that may not yet be available on the NHS, including those for early stage breast cancer, bowel, and lung cancer.” (See www.bupa.co.uk/heartbeat.)
Advocates for breast cancer victims are lobbying hard to get greater access to new medicines via the NHS. Maybe they are aiming too low. Perhaps it’s time for the British government to give the people’s health money to the patients who need it, so that they can buy superior coverage in the private market.
A federal judge has ruled that a District of Columbia law designed to reduce the price of prescription drugs is unconstitutional and blocked its implementation. U.S. District Judge Richard J. Leon said the law, passed this fall, violates constitutional protections of interstate commerce and goes against the will of Congress.
Under the measure, the manufacturer of a drug that cost 30 percent more in the District than in four designated countries (Germany, Canada, Australia, Great Britain) would have to prove that the price was not excessive. The drug company could seek to justify the price based on research-and-development costs, its profit margin or other factors. If the manufacturer failed in that effort, a court could impose civil penalties.
Leon’s opinion said the District law is in direct conflict with federal patent law, in which Congress designed a “carefully crafted bargain intended to provide pharmaceutical companies with incentives to develop drugs. Those incentives include exclusive sales rights for a certain period,” he said. Punishing the holders of pharmaceutical patents in this manner flies directly in the face of a system of rewards calculated by Congress to insure the continued strength of an industry vital to our national interests, Leon wrote.
“This is an important issue and one worthy of a fight,” said Council member and author of the legislation David Catania. “No one suggested it would be quick or easy.”
Or safe. Or sound. Or plausible. Or … legal. But never mind the details.
Catania vowed to continue the legal battle and keep an open mind about revising the law.
That’s nice.
Another Council member, Vincent C. Gray, said, “If this [law] is not the instrument that can get it done, then we need to look at others.”
That’s nice too. May I recommend the councilman look at the recent experiences of Nevada, Texas, Vermont, Minnesota, and Illinois for starters.
After all, it’s nice to share.
As seen in today’s Wall Street Journal …
Europe’s Ailing Drug Industry
By GRACE-MARIE TURNER
December 28, 2005
Just a decade ago, more than two-thirds of all drug research was conducted in Europe. Now, 60% is conducted in the United States. Major European drug makers such as Aventis, Novartis and GlaxoSmithKline have shifted significant portions of their research operations from the Continent to the U.S. and beyond. And human talent continues to follow the research money: Some 400,000 European science and technology graduates now live in the U.S., with thousands more leaving every year.
For all this, European investors, scientists and patients have their own political leaders to blame. Deliberate government policy, in the form of price controls imposed by national health-care systems, is slowly choking off a once-thriving sector.
Europe’s government-run and dominated health-care systems are virtually monopsonies. As the primary buyers in their national markets, they have the power to set drug prices 40% to 60% lower than the free-market prices in the United States. These price controls have a serious impact on innovation.
Research and development are expensive. Researchers at Tufts University in Boston determined that drug makers spend at least $800 million just to develop a new medicine, and there is a high risk that a drug could fail after years of testing or flunk the government approval process. In the United States, companies are allowed to recoup their investments and make a profit by charging a price that incorporates their research costs. In Europe, that is seldom the case.
The loss to research caused by price controls was quantified in a recent study by the U.S. Department of Commerce. The study looked at the impact of pharmaceutical price controls in 11 countries, among them Holland, France and Germany, and found that price controls caused a $5 billion to $8 billion annual reduction in funding for drug research and development.
What could that amount buy? According to the study, it could lead to the discovery of three or four new potentially life-saving chemicals each year. So it’s no surprise that from 1998 to 2002 there were only 44 new drug launches in Europe, compared to 85 in the U.S.
But now is no time for Americans to be smug. Ironically, there is a bipartisan move afoot in the United States to implement the same policies that have dried up pharmaceutical research in Europe by having the government “negotiate” drug prices.
The U.S. Congress passed legislation in 2003 that added a new prescription drug benefit for the disabled and elderly participating in the country’s Medicare program. It also created a novel system to deliver the drug benefit, encouraging private, competing companies to negotiate the best prices they can with drug makers.
Congress included in its legislation a “non-interference” clause that preserves the right of these drug plans to negotiate prices freely with the drug companies, without intervention from the federal government. While Americans have mixed opinions about this gigantic government drug program, one thing is clear: Repealing non-interference would put the U.S. pharmaceutical industry on the European path, yet it is a top priority of liberals who plan to bring up this legislation next year.
If non-interference is reversed, it will allow the federal government to step in and set prices for all 40 million Medicare recipients. Since they consume almost half of all prescription medicines sold in the United States, this would effectively amount to nationwide price controls.
We’ve already seen such policies force drug makers out of Europe. Roche chairman Franz Humer has pointed out that the research-based pharmaceutical companies could just as easily move on to Asia, where technology and education are steadily improving. In fact, Roche has just opened a research center in Shanghai, while other drug makers are flocking to Singapore and India.
Of course, if the U.S. gives drug makers a reason to go on the move again, European governments could make their own pitch by eliminating the interventionist policies that have been undercutting drug innovation in their countries. They just might be able to lure talented drug researchers and pharmaceutical investments back home by recognizing the value of pharmaceutical research — not only in creating new medicines but in reviving a valuable industry.
Ms. Turner is president of the Galen Institute, a health-research organization based in Alexandria, Virginia.
Nevada Attorney General George Chanos has released an opinion concluding that Nevada law prohibits the importation of prescription drugs from Canada unless such prescription drugs have been approved by the Federal Food and Drug Administration.
That’s a safe bet.
The Attorney General’s Office drafted the opinion in response to a legal opinion request from Larry L. Pinson, Executive Secretary to the Nevada State Board of Pharmacy.
The opinion analyzes Senate Bill 5, enacted in a special session of the 2005 legislature, which was intended to authorize the licensing of certain Canadian pharmacies to provide only “FDA approved” prescription drugs by mail to Nevada residents.
That’s a sucker bet.
To pursue the metaphor, state legislators should stop encouraging their citizenry to play Russian Roulette with their health by purchasing medicines from non-FDA approved foreign sources.
The following blog contains non-emotional comments from Dr. Bob Goldberg …
After reading that the FDA approved the first drug for treating kidney cancer in over ten years, a drug that was so effective that the National Cancer Institute told the company that was developing it to stop the trial early, I wondered, “what would Merrill Goozner write.” Goozner, who has dumped on every new cancer drug developed and pissed on Tysabri the drug for multiple sclerosis which is about twice as effective as any other drug for MS on the market for many patients was true to form. Goozner once again blatantly distorts clinical data to assert that the drug, Nexavar, does not prolong life. In fact, many patients lived on average twice as long with end stage kidney cancer (6 months compared to 3 months) compared to people who had other drugs. Now anyone but Goozner, who wants to put new drugs in the worst light possible, will tell you that the average includes people who lived a lot longer than 6 months including those who went into remission. And as we develop genetic tests to identify who responds best to which cancer drugs we will be able to provide Nexavar to people with kidney cancer patients well before the cancer is end stage and treat it as a chronic disease as we are doing with breast cancer. The FDA and NCI rapidly reorganized the clinical trials for this drug around such new science as best it could. And it is in large part for this reason that Nexavar was so quickly approved after so much delay. Going forward the FDA is seeking to use tools that more accurately measure how and cancer drug works and what patients it works for.
But all you read from Goozner is the heart problems associated with the drug and how the Europeans are waiting, waiting and waiting for real survival data. Of course Goozner won’t tell you that the Europeans are still waiting for survival data about Herceptin even as we are using to basically cure breast cancer before it starts in a lot of women in an effort to save money. And he ignored the quote from FDA’s cancer division head Dick Padzur who said, “Rarely do we see a 100 percent improvement in a new cancer treatment.”
Goozner, like Sid Wolfe, who heads up Public Citizen, the group from which Goozner’s garbage flows is more interested in killing drug companies than in saving the lives of people. His life work is in contrast to a friend of mine, Alan Feldman who died five years ago this Hanukkah from kidney cancer. He was an oncologist. But more than that he was one of the kindest and most generous people I have ever known Even as he himself was dying from cancer he treated other patients, offering them hope and care. In the last of his journal entries Alan wrote that he hoped he could live to see the day when a more effective medicine for kidney cancer would be approved. He realized how precious each day was as a doctor, father and friend. My celebration of this Hanukkah will be enhanced by knowing that one his wishes has finally come to pass. But my joy in learning about the approval of Nexavar is tempered by the sadness in knowing that he is not alive to use it on behalf of others.
Bob Goldberg reports in from the Big Rock Candy Mountain.
FDA Moves to Decrease Lead in Candy (AP)
The FDA proposed Thursday a stricter recommended limit on the amount of lead, a highly toxic metal, allowable in certain types of children’s candy. The Food and Drug Administration now recommends that candies eaten by small children not contain more than one-tenth of a part per million lead. That amount of lead does not pose a significant risk to small children, the agency said. “This new guidance level will further reduce an already minimal risk from lead exposure in candy,” said Acting FDA Commissioner Dr. Andrew von Eschenbach.
For those of you thinking such a regulatory action is a well-meaning public health initiative, think again. I have in my possession the off-label responses of Sid Wolfe of Pubic Citizen and Charles Grassley to the FDA candy action. Wolfe of Public Citizen lambasted the FDA action stating “this is an obvious move by the agency to do the bidding of the junk food industry who wants to boost profits during the holiday season in a too-little, too-late effort to pass their poison off as healthy.” Senator Charles Grassley commented that the lead limit was yet another example of how industry is too cozy with the FDA. “If there really was a firewall between businesses and the agency, the lead would stay in and kids would eat less candy. I am demanding every candy maker send me every sample of candy ever sent to the FDA, every letter they ever sent to the FDA, every lab test sent to the agency and every document in the United States in every household in the country with the words lead and candy in them. In fact, if the word is spelled led, I want that document too. And the same goes for that cute stationery and pencils and toothbrushes with the name Candy or Candi on it.”
Texas won’t allow Canadian drugs after all
A new state law intended to help Texas consumers buy less
expensive prescription drugs from Canada was struck down Wednesday by
Attorney General Greg Abbott, who ruled that it violated federal law.
The attorney general said the statute violates the federal Food, Drug
and Cosmetic Act, which “makes it an offense not only to import, but to cause the importation of prohibited medications.”
Abbott, whose jurisdiction covers only Texas law, said similar proposals in Maryland, Tennessee and Vermont have encountered legal challenges.
Can FDA do more to speed the advance of cancer treatments? Of course. But FDA hasn’t been idle. Consider the agency’s existing initiatives to help make innovative therapies available more quickly and at a lower total cost while maintaining high standards of consumer protection.
FDA has already made great strides:
* Reducing drug development times by avoiding multiple review cycles
* Improving the review process through a quality systems approach to medical product review
* Supporting innovation in medical products by clarifying regulatory uncertainty and increasing predictability in product development
FDA has been available and engaged in constant communication sponsors early on in the review process including:
* End of Phase II meetings
* Pre-NDA meeting
* Post-NDA Submission meeting being piloted by the Oncology Division
FDA has requested and approved comprehensive development programs in advance of “Fast Track” designations, helping to ensure clinical trials are properly structured:
* Using newly developed Special Protocol Assessment guidance, product developers work more closely than ever before with the FDA to create phase III studies prior to implementation to gather all necessary information
* FDA’s call for the use of a Continuous Marketing Application enhances sponsor access to early guidance and feedback for Fast Track drugs or biologics intended to treat serious or life threatening diseases, and provides for FDA-sponsor agreement to engage in frequent scientific.
In addition to early and frequent communication, FDA’s quality systems approach to medical product review has facilitated the regulatory review process through:
* The implementation of the Common Technical Document (CTD) and the electronic CTD (eCTD), which uses cutting edge technology and combined with international public health policy to provide better quality, consistency and communication with sponsors. Another key component to this program is the development of new medicines by creating clearer guidance for product approvals in priority areas (e.g., obesity, diabetes and oncology).
* The Special Protocol Assessment (SPA), guidance was created to help product developers design phase III trials that will ensure necessary data is being collected. In addition, the FDA works closely with sponsors to review and approve a comprehensive development program in anticipation of Fast Track designation and the potential filing for Accelerated Approval. This includes phase III confirmatory studies —a major theme repeatedly mentioned as a criterion for accelerated approval.
Overall, these and other initiatives are designed to help the FDA achieve its public health mission of promoting and protecting patient health by reducing time to market for new medical products such as Nexavar — resulting in earlier patient access to safe and effective treatments.
Do more? Sure. But credit where credit is due for important reforms already designed and implemented.
Center for Medicine in the Public Interest is a nonprofit, non-partisan organization promoting innovative solutions that advance medical progress, reduce health disparities, extend life and make health care more affordable, preventive and patient-centered. CMPI also provides the public, policymakers and the media a reliable source of independent scientific analysis on issues ranging from personalized medicine, food and drug safety, health care reform and comparative effectiveness.
