The Press on Pain

Reading the Wall Street Journal’s editorial page is one of the more productive parts of my day. No, I’m not a liberal masochist. It’s just a quick way of keeping up with the latest bulletins from the frontiers of corporate public relations and right-wing think tank quackery.

Journal editorials supporting the drug industry usually combine the least admirable traits of both these schools of thought: Outright falsehoods combined with a misleading use of statistics. The Journal’s musings this week on “the painkiller panic” employed both those tools.

Now, before I launch into a dissection of their editorial and you head for the delete button, let me quickly say that as a long-time practitioner of the craft of journalism, I understand perfectly well that it never pays to argue with someone who buys ink by the barrel. But I’m making an exception in this case because the flaws of fact and logic in the Journal’s editorial are not limited to the right-wing cranks that dominate that page. They are the same flaws one finds in the pages and broadcasts of most news outlets when they cover medical news. So consider this a quick tutorial in how to read or watch what I call the medical hype and hope industry – brought to you almost every week on the covers of Time or Newsweek or the front page of your daily newspaper.

The issue of the moment is the safety of painkillers. Since Merck pulled Vioxx from the market in late October because it raised the risk of heart attacks, Pfizer’s Celebrex and Bextra and generic naproxen (the active ingredient in Aleve and some other over-the-counter pain relievers) have come under similar clouds. The Food and Drug Administration on Thursday announced its scrutiny will now extend to all pain relievers, not just the so-called Cox-2 inhibitors like Celebrex and Vioxx. What’s the poor consumer to think?

The Journal’s editorial exploited this confusion to the hilt. “All drugs have side effects, especially when taken in large doses and over the long term. We already knew that more than 15,000 people die – yes, die – annually from gastrointestinal bleeding caused by drugs like naproxen and ibuprofen, the side effect newer drugs like Vioxx and Celebrex were designed to avoid.”

The Journal wasn’t alone in making this outlandish claim about the deaths from over-the-counter painkillers. Last weekend’s New York Times front page story put “perhaps 16,500 deaths” in its lead. It would appear that lots of people – more than a third the total that die in traffic accidents every year – are being hauled off to hospitals and dying from bleeding ulcers after taking aspirin, ibuprofen and other generic painkillers.

As I’ve reported before in this space, that’s an outlandish claim that’s pretty easy to double check, which no reporter has yet taken the time to do. The Centers for Disease Control systematically tracks the causes of death for the 2 million-plus Americans who die each year. In 2002, the most recent year for which statistics are available, just 4,081 people died of burst peptic ulcers, a number that has stayed remarkably constant over the past decade after falling sharply in the early 1990s. If one includes all forms of gastrointestinal bleeding deaths (upper and lower G.I. track, whatever), the total is still under 8,000. Presumably, quite a few of those deaths were for reasons other than the side effects of pain pills.

Now any death is serious, but it’s interesting to note where the 16,500 number came from. In 1998, when the Pfizer and Merck’s pre-FDA approval marketing campaign for Cox-2s was at a fever pitch in the medical literature and in the press (Time Magazine hailed them on its cover as super aspirins), a Stanford University physician named Gurkirpal Singh published an article in a drug-industry funded supplement of the American Journal of Medicine, a second-tier medical journal. He created that number by taking the deaths from a sample of about 12,000 patients, most whom had severe rheumatoid arthritis and took fistfuls of painkillers every day, and extending the ratio to the 13 million arthritis sufferers that the Arthritis Foundation (itself substantially funded by the drug industry) says take pain medicine for their symptoms. The same was true for the claim that painkillers caused 107,000 annual hospitalizations.

Dr. Singh, identified in the Times article only as a professor of medicine at Stanford, had a handsome photo in the paper last Sunday. But when I called him this week at his place of employment to discuss his findings, he wasn’t in. In fact, he wasn’t listed in the Stanford Medical School directory.

So I called one of his colleagues, Dr. James Fries, himself an arthritis specialist. He told me that he always thought the 16,500 number was far too high. He also said that Dr. Singh was no longer affiliated with Stanford and if I wanted to learn why, I’d better call the dean because he wasn’t at liberty to discuss it. When I asked him if Dr. Singh had taken money from drug companies for his studies, Dr. Fries replied, “Oh, Dr. Singh took substantial sums from drug companies.”

There’s another way to look at Dr. Singh’s (and the Wall Street Journal’s and the New York Times’) number. The original clinical trial that showed Vioxx reduced gastrointestinal side effects compared it to naproxen, a pain reliever long thought to be the most destructive of the digestive tract. The Merck-funded study followed about half as many patients as Dr. Singh. Yet it found no deaths from gastrointestinal complications -- zero.

However, it did reduce the number of gastrointestinal events that were serious enough to require medical intervention. How many were there? For every 1000 patients taking naproxen during the trial, there were 14 serious gastrointestinal events. Vioxx reduced that down to 6. It was this same trial that alerted some physicians – like Dr. Eric Topol of the Cleveland Clinic -- that this new class of drugs might cause cardiovascular problems. He’s waged a valiant struggle to bring this to public attention ever since.

Now back to the Journal editorial. “One of the most frustrating things about the latest news on painkillers is that almost none of the people reporting it understand the concept of relative risk – i.e., that a doubling of adverse events like heart attacks still doesn’t mean that event is very likely.” The editorial pointed out that in the trial implicating Celebrex, a “mere” 15 per 1,000 suffered heart attacks compared to 7.5 taking nothing at all.

I couldn’t agree more with the Journal's logic. It’s time for all medical reporters to begin looking at absolute risks and benefits, not relative risks and benefits. How many times do we read that Drug A cuts your chance of getting a disease in half (relative benefit) only to find out later that for every 100 people taking Drug A, one will get the disease instead of two (absolute benefit).

Of course, the Journal was selective in its use of this principle. All trials that have looked at anti-inflammatory drugs, whether over-the-counter painkillers like ibuprofen or naproxen or the mislabeled “super aspirins” like Vioxx or Celebrex, show they are remarkably similar for treating pain with about 80 percent effectiveness. So their absolute benefit is the same.

The only difference is the side effects – and their price. Using the data from above-mentioned clinical trials, we find that for every 1,000 people taking a pricey, prescription "super aspirin" instead of an over-the-counter painkiller, our medical system has traded 8 fewer ulcers for 7.5 more heart attacks.

Now I ask you, how many Americans, if given all the facts, would trade the low risk of an ulcer for the low risk of a heart attack for the same pain relief, especially when the over-the-counter drugs are one-tenth the price?

Overdosed and Oversold

The following first appeared in The New York Times:

By MERRILL GOOZNER

Washington

IN the early 1960's, Congressional hearings on skyrocketing drug prices went nowhere. But the political logjam was broken when a eagle-eyed doctor at the Food and Drug Administration averted a potential disaster by advising the agency not to let thalidomide into the United States market.

While the final legislation back then had little to do with prices or safety, the new law ushered in efficacy testing and led to the withdrawal of hundreds of drugs of no medical benefit from the market.

Once again, an agency badly in need of reform faces growing popular outrage over drug safety. The F.D.A.'s failure to spot the warning signs that popular painkillers like Pfizer's Celebrex or Merck's Vioxx increased the risk of heart attacks, or its failure to warn doctors and parents about the risk of suicide among children taking antidepressants, has resulted in bipartisan anger on Capitol Hill. Prominent voices have joined the call for an independent drug safety board.

But reform at the F.D.A. needs to go much further if it is to once again become the gold standard of medical oversight not just for consumers but for providers and insurers. Only an updated regulatory system can provide them with the information they need to come up with the right answers.

People confront dizzying choices in health care every day: are brand-name drugs better than generic versions? What are the real costs and benefits of a medical intervention? How serious are the side effects of a drug and how do its benefits compare to, say, losing 30 pounds or going for 10 sessions of therapy? Does an expensive new imaging system or test really provide doctors with critical information?

To make rational choices, doctors and consumers need the F.D.A. and other agencies to be independent arbiters of not just the safety and efficacy of new drugs and devices, but of their relative medical usefulness and economic viability. Moreover, the medical oversight system needs a new ethic - one that scrupulously adheres to a standard that says its studies and decisions have been made entirely free of commercial bias and conflicts of interest.

Sadly, that is very far from the situation today. Drug and device companies sponsor most clinical trials; F.D.A. advisory panels are larded with scientists tied to private companies; corporate user fees help finance the F.D.A. that is conducting reviews; doctors get most of their medical information either from sales representatives of drug companies or corporate-sponsored continuing medical education; and the companies are given primary responsibility for post-marketing safety surveillance of their own products.

To break these ties, there needs to be an independent arm of F.D.A. that contracts with independent clinicians and scientists for the final testing of all new drugs and medical devices. After a company submits its drug application based on safety and early efficacy trials, this arm would design the protocols to learn not just if the new drug is effective versus a placebo, but how it compares to other therapies and how it can be most effectively used. At the same time, the F.D.A. agency would need an adequately financed post-marketing system that would follow through on a drug's safety, using information and financing independent of the drug manufacturers. It should also reimpose the pre-1997 restrictions on direct advertising to consumers, one of the elements that led to vast popularity of Celebrex and Vioxx among arthritis patients.

Congress should also set up an independent agency for conducting comparative trials for thousands of existing therapies. This new center, perhaps housed at the National Institutes of Health, would also evaluate the cost-effectiveness of new technologies and finance the work of scientists who want to test older, off-patent medicines for new uses. And it could oversee the creation and updating of clinical practice guidelines free from commercial sponsorship so that hospitals and doctors can base their decisions on objective evidence.

This new center could also be the data bank for registration of all clinical trials, whether conducted by the public or private sector. This should include the trials' initial goals, the final results and reasons for stopping the trial if that occurred.

The medical profession also has to play a role. It should adopt strict ethics rules that limit the access of drug representatives to doctors' offices, and ban the growing practice by medical institutions of accepting donations from drug makers for continuing-education courses.

Unless the entire oversight system is overhauled, there will be many more fiascos in which risks or long-term side effects are played down or ignored, as they were with Celebrex and Vioxx. Not until the system of medical approval and information is returned to objective hands will doctors and consumers be able to make the wisest and most cost-effective medical choices.

Merrill Goozner, director of the Integrity in Science project at the Center for Science in the Public Interest, is the author of "The $800 Million Pill: The Truth Behind the Cost of New Drugs."

Copyright 2004 The New York Times Company

Celebrex -- the next poison pill?

Flash: Celebrex becomes the latest aspirin substitute linked to increased risk of heart attacks.

Pfizer this morning announced it has stopped a clinical trial for its billion-dollar painkiller Celebrex because it triggered two-and-a-half times more heart attacks than placebo.

It is becoming increasingly clear that heart problems associated with everyday painkillers called Cox-2 inhibitors (Vioxx, Celebrex, Bextra) are what pharmacologists call a "class effect." Every Cox-2 inhibitor on the market has now been linked to increased risk of heart attacks or strokes.

In September Merck pulled Vioxx from the market because of its link to heart problems -- evidence that scientists knew as early as 2001. And a recent review of published literature about Bextra showed a similar link.

It's interesting to note that Pfizer decided to release this information on Friday. In the world of politics, that's the day when savvy politicians release bad news because Saturday's papers get the smallest readership of the week.

But no public relations strategy can rescue the drug industry or its handmaidens in government from the firestorm that is about to break. U.S. consumers have spent billions of dollars for these "super aspirins" in recent years. When they were launched in the late 1990s, it was considered one of the best marketing campaigns ever by industry insiders. Millions of arthritic seniors threw away their over-the-counter ibuprofen bottles in favor of a $90 per month prescription medicine.

Now, a scant five years later, we have the results of that massive transfer of wealth to the makers of these drugs: tragedy for thousands of families (most of whom have no idea why mom or dad suddenly dropped dead from a heart attack) and increased health care costs to care for survivors of those heart attacks and strokes.

And what was the ostensible benefits of these drugs? They were supposed to save people from the occasional ulcers that resulted from taking either aspirin or other arthritis painkillers like ibuprofen and naproxyn.

It's important to remember that this alleged problem was wildly overstated from the start. Fewer than 6,000 people a year die from perforated ulcers or other forms of gastro-intestinal diseases, according to the Centers for Disease Control. And most of these deaths have nothing to do with taking painkillers.

Yet in news article after news article touting the new "super aspirins," reporters uncritically passed along the claim that an estimated 16,500 died each year from taking traditional pain pills. Where did they get that number? From a single academic study funded by the companies selling the newer drugs.

Indeed, if one looks closely at the Merck trial that led to claims that it helped solve the ulcer problem, one sees that the number of reduced ulcers (not deaths from ulcers, but just ulcers) was roughly comparable to the increase in heart attacks and other serious coronary problems.

One can only hope that when an FDA advisory committee meets in February to discuss the Cox-2 issue, they'll include some economic analysis of this public health fiasco. Conservatives like to subject regulations that cost industry money to cost-benefit analysis. What's that ratio when it is all costs and no benefit?

Saving Your Cake and Eating It, Too

The Social Security debate is in full throttle with President Bush’s comment yesterday that he won’t raise taxes to balance the retirement fund’s long-term budget problems.

Instead, he will press ahead with his plan to make those problems worse.

The administration’s blatantly pro-Wall Street agenda (Increase government borrowing to invest in stocks? Would you take a second mortgage to do that?) drew Paul Krugman out of his den, where he had repaired a few months back to finish a book. In two op-eds in the New York Times this week, he attacked the underlying economics and trillion dollar costs of the Bush plan, whose centerpiece is creating private accounts for younger workers by diverting some of their Social Security taxes. That money now goes to current retirees, whose benefits would depend on the increased borrowing.

As a former economics correspondent who is fairly familiar with Social Security finances, I found Krugman's analysis (it's rob-Peter-to-pay-Paul with a juicy slice going to stock brokers) compelling. But economic logic is not going to win this debate. This country is run by people who have no respect for facts or logic and are perfectly willing to manipulate the “he said, she said” ethos of daily journalists to totally confuse the general public about what’s at stake in Social Security privatization.

We’re already getting a sense of how the press will operate in this debate. The Times early this week ran an intriguing story out of London about the failures of that country’s attempt at setting up private retirement accounts. People are getting less money than anticipated and poverty among the elderly is growing. You’d think that would be front page news, given the emphasis this administration is putting on moving forward with its privatization agenda. Nope. It ran in the Business section, and not on its front page, either.

The short-hand being adopted by some reporters shows that inconsistent language and inaccurate summaries will plague most accounts. Today’s Wall Street Journal favorably quotes Bush economics advisor Gregory Mankiw, a former Harvard prof, claiming their proposed change in the formula for computing workers' future benefits “would save huge sums over time, while still keeping pace with inflation.”

Save money and still keep up with inflation? That sounds like saving your cake and eating it, too. How can that be?

What that quote and the rest of the story fails to mention is that Bush’s proposed change would eliminate consideration of what you earned over the years when calculating your initial benefit. If Bush gets his way, all future Social Security recipients will get the same benefits as today’s beneficiaries. The only adjustment will be for inflation.

Here’s what that means in practice. Every year of your working life that your wages increase faster than inflation, the Bush administration will cut your Social Security benefit. So instead of getting 20 or 30 percent of your final wage as current retirees get, it will be down to 10 or 15 percent by the time you retire. How’s that for a deal?

It’s time for some honest reporting about what this administration is saying. Alas, that would require thought, analysis and a willingness to challenge falsehoods. Among the press, these skills that have been in short supply in recent years.