From the (London) Times Higher Education Supplement

A slightly edited version of this opinion piece will appear Thursday in the Times of London Higher Education Supplement:

By Merrill Goozner

The senior citizen drug benefit signed into law by President George W. Bush last fall guarantees that Americans will continue to pay the highest prices in the world for pharmaceuticals. Though European, Canadian and Japanese health services establish formularies and negotiate reasonable prices for consumers, the new law specifically prohibited the U.S. government from doing the same.

Why did a government facing enormous deficits deny itself the negotiating power that comes from being the largest buyer in the marketplace? The Washington lobbying muscle of the large pharmaceutical companies played a role, of course. But drug industry pressure wouldn’t work unless it was backed by a powerful argument. Most legislators believe industry when it says that Americans must continue to pay high prices or the research and development that makes the U.S. pharmaceutical industry the world’s most innovative and productive will dry up.

The drug industry’s innovation argument rests on several key assertions. First, it assumes industrial labs are the primary source of medical breakthroughs. It further assumes that new therapies for as yet incurable diseases like senile dementia, many cancers and crippling arthritis inevitably depend on generous funding of industry’s R&D labs. And it concludes with the assertion that it costs on average $800 million to develop a new drug, a number supplied by an industry-funded study.

Each of these arguments is false. In an era dominated by genomics and

microbiology, medical innovation depends more than ever before on early stage research that focuses on understanding of the basic causes of disease. Before developing a drug, scientists must first learn the complex protein chemistry of the disease. Within this cascade of biochemical events, scientists must then identify and validate a molecular drug target. Only then can a drug be developed.

This is arduous work that rarely succeeds. Positive results cannot be willed into existence. Breakthroughs in understanding almost always depend on the unplanned and unpredictable interplay of basic science.

Moreover, virtually none of this work takes place in industry labs. Most takes place at universities, non-profit labs or in the public sector, which in the U.S. are mostly funded by the National Institutes of Health, comparable to Great Britain’s Medical Research Council.

Without this basic scientific understanding, curing disease is impossible, especially when it comes to the degenerative diseases of aging. Yet the global pharmaceutical industry is pouring billions of dollars into research in the name of pursuing cures for these diseases. Where does it go?

For many firms, a primary activity of their R&D labs is developing new drugs that mimic the actions of drugs already on the market. Perhaps the old drug is coming off patent. Or the company needs an entry in a lucrative market now dominated by one of its rivals. A survey of all drugs approved by the U.S. Food and Drug Administration in the 1990s found that more than half fell into this “me-too” category.

In the U.S., a substantial portion of the industrial research dollar also gets devoted to funding clinical trials that provide little meaningful information for physicians. They are designed to get more doctors prescribing the newly approved drug – so-called seeding trials. Sometimes these trials are published in second-tier medical journals, which can then be reprinted and handed out by the some 90,000 sales representatives that visit physicians’ offices in the U.S. every day.

Indeed, if one discounts for wasteful research that adds nothing to physicians’ armamentarium for fighting disease, one could cut the industry’s estimate of what it costs to develop a new drug at least in half.

This is not to say that once government-funded basic science comes up with a valid drug target, industrial chemists do not sometimes play a crucial role in developing a drug that can inhibit that target. And industry largely funds the clinical trials needed to prove a drug’s safety and efficacy. But even in this arena, it’s increasingly the case that publicly-funded researchers are taking the lead in coming up with innovative technologies and using technology transfer laws to funnel their lead compounds, monoclonal antibodies and recombinant proteins to small biotech firms willing to gamble on developing the drug.

The debate over U.S. prescription drug policy has gone global. U.S. trade representatives are now arguing that European consumers are free riding on the U.S. innovation system. They say world prices must rise so U.S. prices can come down. The reality is that the U.S. can lower its drug prices to those of the rest of the advanced industrial world without jeopardizing the hunt for the next generation of cures.

Merrill Goozner, author of “The $800 Million Pill: The Truth Behind the Cost of New Drugs,” directs the Integrity in Science Project at the Washington-based Center for Science in the Public Interest.

Rx Sanity

Reading the reviews can get you in trouble, but reading an unsolicited reader's blurb on Amazon.com led me to a fascinating website: RxSanity.org. The lead essay, "The Battle Over Americans' Rights to Affordable Reimported Prescription Drugs," provides an incisive analysis of the U.S. government's refusal to protect consumers here against drug industry price gouging.

The site provoked this thought: Isn't it ironic that when laid off steelworkers and computer programmers complain about imports and outsourcing, they are branded as protectionists. But when these same Americans clamor for free trade in drugs from Canada, their government "protects" them from allegedly unsafe products. I guess that tells us which industry is running the more effective protection racket.

Medicare Drug Bill: Now It's $599 Billion

You may recall the sad saga of Medicare actuary Richard Foster, whose estimates for the cost of the prescription drug benefit were withheld from Congress during last year's debate. It turns out that at least one estimate generated by his office for the 10-year tab totalled $599 billion -- nearly 50 percent higher than the figure provided by the Bush administration.

The higher figure was revealed today by Rep. Henry Waxman (D-CA) and 18 other representatives in a letter sent to Health and Human Services Secretary Tommy Thompson. They blasted Thompson for continuing to withhold documents in their ongoing probe of alleged administration lies during the debate. "Information was actively suppressed by the administration," they wrote. "This is a very serious breach of the integrity of the legislative process."

According to the Democrats, the $599 billion figure was contained in an Office of the Actuary estimated dated June 11, 2003. Two weeks later, White House spokesman Ari Fleischer, in outlining the bill's prospects, told reporters that the fact "the president's proposal . . . has been accepted as a $400 (billion) proposal is helpful."

This is about more than partisan bickering. Though the drug bill's actual costs keep going up, it provides woefully inadequate financial support for seniors. Why? Because in writing the bill, Republicans in Congress prohibited Medicare from doing anything about skyrocketing drug prices. The bill forbids the government from using its purchasing power to negotiate lower prices, forbids the use of formularies (which could steer consumers to generics), and does next to nothing to give seniors and physicians better information about the most cost effective medicines.

In other words, the administration first lied to Congress, and then wrote a bill that turned a subsidy for seniors into a subsidy for Big Pharma. If prices over the next ten years rise at the same pace as they have over the last five years, most seniors will wind up paying more for prescription drugs in ten years than they pay today.

Review: Dramatic change in the drug industry is inevitable

A brief review of The $800 Million Pill (with a nice picture of the book jacket cover) appeared in the Sunday business section of the Washington Post. S.P. writes that "despite the pharmaceutical industry's desperate efforts to keep things as they are, it is becoming clear that the way drugs are priced, and drug research is financed, will change dramatically over the next decade."

There's a pattern in the early reviews. (For my response to previous reviews, click here.) Reading the book convinces reporters that the industry engages in widespread skullduggery in the name of innovation. The reviewers then raise minor quibbles.

If this pattern holds, the book will have succeeded in my fundamental quest: To change the terms of the debate regarding drug pricing and its relationship to pharmaceutical innovation. That, in this author's humble opinion, will be a tremendous victory for those fighting for fair drug prices and for new cures.

NYC Appearances

I'll be making a round of appearances in New York City on Thursday and Friday. WNYC's Leonard Lopate will host a discussion of The $800 Million Pill at noon Thursday, and I'll be signing copies of the book at Labyrinth Book Store on 112th Street near Columbia on Thursday evening. Then on Friday, I'll be signing books at Columbia's Low Library from 7 p.m. to 10 p.m. along with other graduates of the J-School who've published books in the past year. If you're in town, stop by!

Follow the Evidence

Today’s Journal of the American Medical Association offers dramatic confirmation of the value of conducting comparative clinical trials. Two years ago, the federal government released the results of an $80 million, eight-year trial comparing blood pressure control medications. Lo and behold, generic diuretics proved to be just as effective as more expensive (because still on patent) ACE inhibitors and calcium channel blockers, the drugs doctors most often prescribe.

Michael Fischer and Jerry Avorn of Harvard Medical School decided to match those findings against what physicians are doing in the real world, where pharmaceutical industry marketing and not “evidence-based medicine” drives physician prescribing decisions. They reviewed records for over 133,000 patients treated for hypertension in 2001 under one state’s drug assistance program. Had physicians in the program used evidence-based guidelines, nearly 40 percent of the patients could have been switched to a cheaper medicine. It would have saved the program over $11 million or nearly a quarter of the government’s expenditures.

The authors then extrapolated their findings nationwide. Their conclusion: “Adherence to evidence-based prescribing guidelines for hypertension could result in substantial savings in prescription costs for elderly patients with hypertension that would amount to savings of about $1.2 billion nationally.”

In the Marketplace

The $800 Million Pill got a major publicity boost yesterday from my appearance on Marketplace. To hear the interview with Kai Rysdal, click here (you'll need Real Audio to listen).

The Economist: "Pill-gotten gains"

The April 10th edition of the Economist magazine offered a short but significant review of "The $800 Million Pill." Like Business Week, the unsigned review accepts the essential accuracy of my analysis: that much industry R&D is wasted, and that significant breakthroughs almost always originate in the public sector. But unlike its U.S. rival, the British reviewer read the concluding section of the book with enough care to suggest its key reform -- comparative clinical trials that might dissuade drugmakers from pursuing me-too drugs -- doesn't go far enough. "Alas, such are the powerful entrenched interests in drugmaking that it will take something stronger than a dose of information to calm the current fever over pill-pricing," the review concluded.

Memo to the Economist from this side of the pond: Even getting this one change passed in the current U.S. political environment would be a major victory, and a start toward more comprehensive reform of the medical innovation process.

Business Week Review: I'm right, just not right enough

Business Week gave “The $800 Million Pill” a mixed review in this week’s (April 19th) edition. Reviewer John Carey calls the book “provocative but insufficiently reflective.” I failed, in his view, “to explore further solutions to th(e) dilemma” that drugmakers’ self-interest and public health don’t often coincide.

I’ll return to that criticism. But I first would remind readers that it was never my intention to resolve the drug industry’s moral dilemma or convince industry executives to focus more of their R&D budgets on socially useful products.

What I set out to do (and this is clearly outlined in the introduction) is to debunk the myth, which the drug industry propagates on television, in newspapers, in the halls of Congress, and from the bully pulpit of the executive branch, that unless the industry is allowed to continue charging exorbitant prices and raking in huge profits, innovation will dry up. On that score, I succeeded entirely, in Carey’s view. “He proves that Big Pharma need not require $800 million to develop an important new drug” and that “many drugs were created with government funding – then were sold to consumers at sky-high prices.”

But then he goes on to ask: “Is it really a shock that companies spend a big chunk of their R&D budgets on drugs that sometimes show no clear medical advantage but that bring surefire profits?” The goal of business, after all, is to make money.

Of course it comes as no surprise. But it is not common knowledge. And public policy is being driven by the myth.

I’m a reporter, not an investor. My goals are to counter industry lies, protect the public purse, and expose practices that make health care unaffordable – practices, I might add, that receive scant attention in the pages of Business Week (this has nothing to do with it being a business publication; some of the finest journalism on drug industry practices gets reported in the Wall Street Journal).

That said, I would like to quibble with Carey’s assertion that I failed “to explore further solutions to this dilemma” of how to make drugsmakers self-interest coincide with public health. “Should drugmakers be held to a higher standard than, say auto makers?” he asks at one point. “Do we need new regulations or incentives to prod the industry into focusing more if its R&D on important medical needs?”

I recommend that Carey go back and reread my last chapter. It is chock full of suggested reforms aimed explicitly at getting drug companies to focus more of their R&D budgets on significant medications.

Moreover, as far as holding drugmakers to a higher standard is concerned, allow me to repeat a criticism from an industry insider included in both the opening and closing chapters of the book. It’s not a moral question. Unless the big drug companies figure out how to tackle pressing medical needs, Hoffmann-La Roche's former R&D chief Jurgen Drews wrote in 1999, they will go the way of the dinosaurs. As I said in a Washington Post op-ed last December, when drug consumers and their representatives are properly informed and empowered, they will force the industry to change.

It's A Girl!

And now for a purely personal note: My daughter Rebecca, son-in-law Chris, and grandchild Rachel were joined this morning by grandchild Sarah, who weighed in at 6 pounds, 7 ounces and 19 1/4 inches long. Mazel Tov to the Kuepers family of Naperville, Illinois!

Love,
Grandpa

BMJ on Antidepressants and Kids

Tomorrow's British Medical Journal (April 10th edition) has a stinging editorial condemning the widespread use of antidepressants in children. The issue contained a review of seven randomized controlled trials that found the reported results were often misleading by downplaying serious side effects and overstating benefits. Moreover the study asserted that pharmaceutical companies, which funded at least three of the four major trials in the study, may have failed to disclose increased suicidal activity related to the use of these drugs. Conclusion: Biased reporting and overconfident recommendations may be misleading doctors, patients, and families.

On February 2, the Center for Science in the Public Interest released its own report on the biased record on antidepressant use in children. Click here to read "SSRI Use in Children: An Industry-Biased Record."

The $800 Million Trial

As a former member of the working press, I can speak from personal experience about the lack of critical thinking that accompanies most daily journalism. But today's Wall Street Journal front page story on Pfizer's new cholesterol drug was simply astonishing in its naivete.

The story claimed Pfizer will spend about $800 million on clinical trials to bring its next cholesterol blockbuster to market. The drug, called torcetrapib, raises "good" cholesterol.

Why will this trial cost so much? Deep in the story, the Journal dutifully repeats company claims that it will test 13,000 people for five years, with 3,000 of the patients getting ultrasound imaging tests to reveal what's going on inside their arteries. These tests "will eat up much of the $800 million."

In an email communication, Scott Hensley, one of the Journal writers, indicated some of these ultrasound tests will require cardiac catheterization, an expensive procedure. Okay, let's do the math. Ultrasounds cost about

$250. If each one of those 3,000 patients gets four ultrasound tests per year for the five years in the test, that comes to $5,000 per patient or $15 million. Let's double that cost to $30 million just to be conservative. Then let's throw in $10,000 per patient for cardiac catheterization. That's another $30 million. Let's round the whole testing portion up to $100 million just to be safe.

That leaves $700 million for drugs, doctor visits, record keeping, massaging the data, and whatever else accurate, authoritative clinical trial design requires. With 13,000 patients in the test, that comes to nearly $54,000 per patient.

Jamie Love of the Consumer Project on Technology has done considerable comparative research on the cost of clinical trials. This afternoon, via email, he offered these numbers for the average cost per patient in clinical trials:

* From a Tufts University study: $23,572 (this adjusts the costs for the time value of money)
* From a TB Alliance study: $644 to $22,000 (also time value adjusted)
* From a BMS Oncology study: $10,000
* An NIH Study: $6,202
* DataEdge survey for all Phase III trials (final FDA approval trials like the Pfizer study on cholesterol): $5,465

I suggest Pfizer simply turn the whole process over to the government. They'd save themselves and consumers a lot of money.

But I'll give Dr. Love the final word: "$800 million for a trial is absurd, but since these things are faithfully reported as if they are true, why should they stop making these claims?"

A Good Discussion About Losing One's Mind

"Better Treatments Soon Are Called Unlikely," the New York Times reported today. The subject was treating Alzheimer's disease. There are a handful of drugs on the market, but it turns out their benefits are minimal.

The part of today's story that was most shocking was the recounting of last July's report in The Journal of the American Geriatrics Society that claimed Pfizer's drug Aricept could delay a patient's entry into nursing home care for nearly two years. Critics in as yet unpublished letters to that journal said the study's data did not support the claim. The study's authors were paid -- you guessed it -- by Pfizer. (For a great discussion of why it is getting harder and harder to trust medical journals, see Shannon Brownlee's story in the April Washington Monthly, "Doctors Without Borders: Why you can't trust medical journals anymore."

Alzheimer's is the "dread disease" of aging. Nothing strikes greater fear into Baby Boomers' hearts as they contemplate their golden years. But despite the billions of dollars poured into industry's coffers to pay for a research and development, we still only have a handful of drugs whose chief benefit is to the companies' bottom lines, not their patients.

The sad fact is that scientists still don't know what causes Alzheimer's or even how the cognitive brain functions whose impairment we call Alzheimer's work. If you don't understand the basic science of natural functions like memory and cognition, how is it possible to come up with drugs to combat age-related impairments in those functions?

As if to counter the Times story, C-Span this morning interviewed the chairman of Pfizer. He complained about senior citizens importing low-cost drugs from Canada. He said it would choke off innovation in the U.S.

The truth is that we're wasting our money when we subsidize drug companies with high prices in the vain hope that they will come up with the next generation of cures. The government, which is about to spend $540 billion on drugs for senior citizens over the next ten years, would be better off spending its marginal health care dollar on more research into the basic causes of the diseases that most concern us. Because until we know why we get sick, there is no possibility of coming up with a cure.

The Bush Administration's War on Clean Air

The New York Times Magazine's cover story today exposes how the Bush administration and the electric power industry conspired to gut the Clean Air Act. The rules in question involved New Source Review, which until Bush's EPA radically liberalized them forbade companies from substantially rehabilitating coal-fired plants (and thus vastly increasing their electricity output and use of coal) unless they installed scrubbers. Coal-fired plants are major contributors to acid rain, ground-level ozone, soot and mercury pollution, which has been much in the news lately.

The article didn't cover the latest news. A number of state attorneys general have sued the government and won a temporary stay of the new rules. Meanwhile, the Republican-controlled Senate Environment Committee last December asked the National Academies of Science -- the organization whose studies are usually considered the gold standard on scientific investigations -- to study the impact of the rules as a sop to Sen. John Edwards (D-N.C.), whose state is a victim of ambient air pollution from power plants in states to its west.

But something strange is happening with that study. The NAS appointed a prominent global warming skeptic who has written for the right-wing Hoover Institution to chair the panel. Princeton University physicist Dr. William Happer's other interesting credential is that he was fired from his post as chief of research for the Department of Energy by the incoming Clinton administration because of his views on global warming.

In late March, several former EPA enforcement officials wrote NAS to protest Happer's appointment, and asked that Happer be removed from the panel. In my role as director of the Integrity in Science project at Center for Science in the Public Interest, I uncovered Happer's appointment and informed the broader environmental community about his impending role.

The question now is whether the NAS will allow someone with preconceived biases and who may hold a grudge against environmentalists chair one of its prestigious panels. Is this another case of the Bush administration manipulating science?

It May Not Be A Great Test -- But It's My Test And I'm Sticking With It

by Merrill Goozner

With a quarter million Americans with normal cholesterol levels dropping dead of heart attacks each year, it would be nice to have a simple test that could predict a person’s vulnerability. Some medical scientists think they’ve come up with the answer.

It’s called C-reactive protein, an inflammatory agent in the blood that springs into action when something in the body gets damaged. Proponents of the C-reactive protein thesis think people with elevated levels are at risk of sudden heart attacks. They’ve published a few studies, and garnered lots of attention over the past few years by suggesting a new biomarker of heart failure risk – the next cholesterol – is at hand. A number of physicians have even begun routine testing of their patients for C-reactive protein.

But today’s New England Journal of Medicine threw a damper on the C-reactive protein thesis. A British study suggested the marker is at best a moderate predictor of sudden heart failure. “Recommendations regarding its use in predicting the likelihood of coronary heart disease may need to be reviewed,” the authors concluded.

Proponents immediately leaped to its defense. The most often quoted source was Dr. Paul Ridker of Harvard Medical School and chief of the cardiovascular unit at Brigham and Women's Hospital in Boston. He told the Associated Press, the Wall Street Journal and other publications that inflammation is a strong risk factor for sudden heart failure and the C-reactive protein test is the best way to spot it. “My concern is that even in the face of overwhelming evidence that this inexpensive blood test works, we are at risk of moving backward rather than forward,” he said.

A healthy debate among research scientists? Perhaps. And, if you’re a certain age and person at risk (maybe your dad died of a heart attack), you’re probably thinking, the heck with those Brits, it’s time to go get the test.

But let’s play a little mind game. What if I told you Dr. Paul Ridker of Harvard owns the patent to using C-reactive protein as a biomarker of heart disease and it’s licensed to companies making the test. And what if I told you his research has been funded by drug companies that make statins, which lower cholesterol and may be used to combat high levels of C-reactive protein.

Would it change your mind? Would it at least give you pause? Unfortunately, you won’t get the answer to this mind game by reading the papers. Unlike medical journals, news outlets rarely report conflicts of interest when they quote prominent researchers. But you can get the answer yourself. Just go to the Patent and Trademark Office website (http://www.uspto.gov/patft/index.html) and put patent number 6,040,147 into the search engine.

You might be shocked by what it turns up. But in this age of hyper-medical entrepreneurialism, you won’t be surprised.