Latest Drugwonks' Blog
An article from today’s WSJ that spells out in very stark terms the different social contracts at play in the UK and the US.
Britain Stirs Outcry by Weighing
Benefits of Drugs Versus Price
Government Arm Finds Pills
For Alzheimer’s Too Costly,
Angering Patients, Pfizer
Ms. Dennis, 80, Joins Protest
By JEANNE WHALEN
Staff Reporter of THE WALL STREET JOURNAL
November 22, 2005; Page A1
LONDON — Millions of patients around the world have taken drugs introduced over the past decade to delay the worsening of Alzheimer’s disease. While the drugs offer no cure, studies suggest they work in some patients at least for a while.
But this year, an arm of Britain’s government health-care system, relying on some economists’ number-crunching, said the benefit isn’t worth the cost. It issued a preliminary ruling calling on doctors to stop prescribing the drugs.
The ruling highlighted one of the most disputed issues in medicine today. If a treatment helps people, should governments and private insurers pay for it without question? Or should they first measure the benefit against the cost, and only pay if the cost-benefit ratio exceeds some preset standard?
The U.S. generally follows the first course. Even the most cost-conscious insurers say they’ll pay the price if a drug works and there aren’t other options. Britain openly and unapologetically adopts the second course. If a drug or type of surgery costs a lot and helps only a little, it says no.
“There is not a bottomless pit of resources,” says Phil Wadeson, finance director for the National Health Service unit that oversees hospitals and doctors’ offices in Liverpool. “We reached the point a while ago where there is far more medical intervention available than any health-care system can afford.”
The decision on the Alzheimer’s drugs has sparked protests from pharmaceutical companies including Pfizer Inc. and Eisai Co., which co-market the leading Alzheimer’s drug, Aricept. They say Britain is using a flawed economic model and will end up spending more on nursing-home care. More than 8,000 patients and caregivers sent angry letters to the National Institute for Health and Clinical Excellence, or NICE, which made the cost-benefit analysis.
NICE “has this strange mathematical formula they put heaven knows how many numbers into and out comes: ‘Yes, it’s affordable,’ or ‘No, it isn’t,’ ” says Antony Dennis, a Web-site designer in the village of Ramsbury whose mother takes Aricept. “Things like the relationship my mum has with her grandson are probably not easy to put into that formula.”
NICE’s decision, first announced in March and reaffirmed in June, applies only to new Alzheimer’s patients and isn’t final. Following the protests, the institute set a meeting for next month at which drug makers will try to show that the Alzheimer’s drugs are cost-effective in at least some patient groups. Until then a previous directive from January 2001 that recommended the drugs remains in force.
NICE doesn’t have the power to force a doctor to prescribe in a certain way. Its decisions are officially just guidance. But in practice, if the institute chooses in December to reject the Alzheimer’s drugs, it is likely to choke off prescriptions for new patients across the United Kingdom (except Scotland, which has its own health system). That’s because most British doctors are employees of local units of the National Health Service such as Mr. Wadeson’s in Liverpool. The local units must keep costs within an annual budget. When NICE says a drug doesn’t pass muster, doctors are under pressure to avoid it and let the local funds be used elsewhere.
Since NICE was founded in 1999 it has reviewed 93 drugs, surgical procedures and other treatments, starting with those it feels are most in need of a rigorous cost-benefit analysis. In eight cases it has called on doctors to stop prescribing treatments because their benefits were judged not to be worth the cost. Rejected treatments include Kineret, a drug from Amgen Inc. for rheumatoid arthritis. In 57 cases it has recommended restricting use of a treatment. It said Eli Lilly & Co.’s Evista should be prescribed only for osteoporosis patients who can’t take another class of drugs.
In 28 cases NICE encouraged full use of a treatment, even if it costs more. Andrew Dillon, NICE’s chief executive, says this demonstrates that the institute’s aim isn’t to save money but to make spending more effective.
Still, Britain spends far less than the U.S. on drugs, not only because of usage restrictions but also because the government sets limits on the profits drug companies are allowed to make in the U.K. In 2004, the National Health Service’s drug bill, including Scotland, came to about $17 billion. Even after adding in out-of-pocket costs, Britain’s per-capita drug bill is less than half of that in the U.S. — about $340 a year per Briton versus about $800 per American based on IMS Health figures.
In Britain, the Alzheimer’s drugs cost about $1,500 a year per person. The total cost to the National Health Service is a little over $100 million a year. The money goes mainly for three drugs: Aricept, Exelon from Novartis AG, and Reminyl from Shire Pharmaceuticals Group. All three are available in the U.S. and covered by most plans under the new Medicare drug benefit. Reminyl is sold in the U.S. by Johnson & Johnson under the name Razadyne.
The drugs are thought to work by maintaining supplies of a chemical involved in the brain’s information processing. Since Aricept went on the market in 1997, the drugs’ global sales have risen above $3 billion a year, according to IMS Health. However, they don’t address the still-unknown underlying cause of Alzheimer’s, which gradually destroys a person’s memory and ability to reason and carry out daily activities. Ultimately the disease is fatal.
While studies aren’t clear-cut or unanimous, they generally suggest the drugs have a short-term effect in delaying the worsening of the disease and may even improve cognitive function temporarily for a minority of patients. Over several years, the effect seems to wear off. One study published this year showed that patients with mild cognitive impairment who took Aricept had a lower risk of progressing to full Alzheimer’s disease than patients taking placebo during the first year of the trial. But after three years the Aricept patients were no better off.
For British health authorities, the combination of high cost and apparently limited efficacy made the Alzheimer’s drugs a natural target of a detailed investigation by NICE, the institute charged with determining whether drugs are worth the money. NICE had already done a cost-benefit analysis and concluded in January 2001 that the drugs were worth paying for. This time it used different methodology and took into account new clinical-trial data.
Last year NICE hired a group of health economists at Southampton University to create a financial model. Using data from clinical trials, the model sought to measure how much benefit patients taking medication would receive over a five-year period compared with those not taking medication. It looked at some of the main benefits medicated patients received — improved cognition, improved quality of life, and a delay in the need for nursing-home or other full-time care.
Following NICE’s standard procedure, the economists then converted those benefits into what is called a “quality-adjusted life year.” This measure, known as a QALY or “kwah-lee,” is used by health economists around the world including in the U.S. A QALY assigns a score between zero and one to a person’s health. A person at zero is dead. A person at 1.0 is in perfect health. If a drug that costs $1,000 extends a person’s life in perfect health for one year and then the person dies, the drug’s cost per QALY is $1,000. Toting up all the numbers, the economists concluded that the Alzheimer’s drugs each cost more than $100,000 per QALY. Typically, NICE believes that drugs shouldn’t cost more than $50,000 or so per QALY, although it doesn’t set a firm line.
Data in hand, the institute convened a panel of doctors and other medical professionals in January of this year to make a recommendation. The panel was sharply divided. Patients’ families and drug companies were arguing that the Southampton University team failed to include some intangible benefits in its analysis such as the reduced burden on caregivers. Patients taking the drugs, they said, were more sociable and less dependent.
Ultimately the panel voted 12-8, with one abstention, to reject the drugs. It concluded that they were “outside the range of cost effectiveness that might be considered appropriate for the NHS.” The decision was announced in March.
Mr. Dillon, NICE’s chief executive, calls it a “very difficult decision” but defends the process of measuring how much an improvement in someone’s life is worth in monetary terms. “NICE has got a responsibility to act on behalf of the whole community, to make decisions about the best way to allocate a finite resource,” says Mr. Dillon. “We have to step back and look at just how much benefit is being obtained from the money the health-care system would have to pay.”
Within weeks of the NICE ruling in March, the Alzheimer’s Society, a patient-advocacy group that receives drug-industry funding, mobilized more than 500 patients and their families to protest discrimination against dementia sufferers. Across from the Houses of Parliament in London, they assembled around a giant inflatable elephant — the society’s symbol — and shouted: “They say cut back, we say fight back!”
Among the protesters was the Dennis family, who traveled by train from a village in Wiltshire. Joan Dennis, 80, began taking Aricept after being diagnosed with Alzheimer’s in January 2003. She hasn’t improved since then, but her doctor and family credit the daily doses of the drug with staving off further decline.
“Without them we are totally convinced that mum would not be in a state to look after herself at all,” says her 43-year-old son, Antony, whom she calls “Ant.” Ms. Dennis will be able to keep taking Aricept because any NICE ruling would only apply to new patients.
Chatting in Antony’s kitchen on a recent afternoon, Ms. Dennis couldn’t remember whether she had eaten breakfast that morning. But she is still able to live on her own, in a row house a five-minute walk away, and cooks her own meals and pays her own bills. Little signs posted around her house help her keep life on track. After forgetting a pan of ground beef on the stovetop last year and burning it to a crisp, she taped several pieces of paper to the wall: “Make sure cooker is switched off.” Another sign stuck to a kitchen cabinet above the phone says, “Don’t call Ant unless it’s pretty urgent.” Before she posted that reminder, Joan says she would sometimes call Antony dozens of times a day to ask about “silly” things she was worried about.
Antony believes the drugs have given his mother the energy to spend time with her youngest grandson, Toby, who is 3. She often reads to him from a brown velvet sofa in her living room. During the protest march in London, Toby carried a placard that said, “I love my Grandma.”
In June, NICE gathered its panel of experts again. They heard officials from the Alzheimer’s Society give the results of a survey of 4,000 patients and caregivers. The survey found 73% of them felt the drug treatments had worked in their cases. The committee declined to change its decision. Later, though, it scheduled another meeting for Dec. 20.
A Hard Case
Pharmaceutical companies will have a chance at the December meeting to argue that their drugs offer especially significant benefits for some groups of Alzheimer’s patients. However, that is a hard case to make because studies offer little evidence for what type of patient does best on the medication. The panel may decide to issue a final rejection of the drugs at that meeting. Companies or patients could still appeal the decision to a separate appeals commission.
Some doctors say they’ll continue prescribing the drugs until local officials force them to stop. “As someone who’s actually seen patients — unlike the epidemiologists and health economists who see this as an incredible waste — I know these drugs work,” says David Wilkinson, a doctor who treats dementia patients in southern England. “If the drug companies hadn’t priced them as they have we wouldn’t be in this bloomin’ argument.”
Pfizer says it and its partner, Eisai, reduced the price of Aricept by 7% on Jan. 1, 2005, under an agreement with Britain’s Department of Health. Paul Hooper, managing director of Eisai in the U.K., points out that the drugs are the “same price as a pint of beer” per day.
Mr. Dillon, the NICE chief, notes that doctors were on the committee that declared the drugs not cost-effective. “This isn’t a bunch of technocrats in an office block in London making a decision,” he says.
Dead people are very cost efficient. They have no need for costly hospital procedures, pharmaceuticals, or home care. On the other side of the pharmacoeconomic spectrum are people who suffer non-fatal medical events like a heart attack or stroke — and survive due to every kind of help our health care system can provide. Such interventions are often both extensive and extended. But we are compassionate and civilized and value life. Individually and collectively we choose and support expensive care over expedient demise. That’s why it’s so urgent that we recognize the exigent issues surrounding our nation’s ill-placed focus on acute care while chronic care issues remain precariously in the background — in terms of both policy and press coverage.
The recent IDEAL study is only the most recent case-in-point. After a slamma JAMA editorial extolling the findings that Lipitor (80mg) provides incremental reductions in multiple endpoints including non-fatal heart attacks (a whopping 17% decrease in fatalities) and cardiovascular events in high-risk patients compared to simvastatin (20/40 mg) — the mainstream press played down the whole study as only marginally significant. Well, life is lived between such margins — and when it comes to CVD, those margins are pretty wide. In 2005, $393.5 billion was spent on CVD — nearly twice the amount spent on cancer care. Between 1970 and 1990 life expectancy in the US rose an astounding 6.2 years — due largely to new therapies for dealing with CVD.
Today we have the opportunity to further extend our ability not only to live but also to thrive at a high level of performance. And the impact on our health care system — not to mention our society will change the world … but only if we pay attention.
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.