Kolata: Ignoring the Real Story

Once again New York Times health reporter Gina Kolata has outdone herself with getting facts wrong and presenting an incomplete picture of scientific studies. In yesterday’s Week in Review, she debunked a recent NIH-funded study out of Great Britain that showed Americans self-reporting worse health than their British counterparts.

She argued that we're probably sicker because we test and screen for sickness to a far greater extent than our British cousins. She also points to “disease mongering,” which medical providers like the pharmaceutical industry use to convince many Americans they are sick.

Her bottom line was that the difference in life expectancy (77.6 in Great Britain and 77.1 in the U.S.) was “almost identical.” Pretty clever -- using a progressive critique of the "over-medicalization" in our health care system to bash the progressive idea that we're somehow not getting bang for our buck when it comes to health care spending.

I immediately because curious about her data. Were the Brits and us really about the same? So I went to the OECD website this morning and discovered that the 30 member nations’ last report (2003 data) showed the United Kingdom at 78.5 years life expectancy at birth compared to 77.2 in the U.S., a substantial 1.3 years difference. Indeed, UK was precisely at the midpoint (Japan was highest at 81.8; Turkey lowest at 68.7) while the U.S. was tied for 21st. At the glacial pace at which these numbers change, this puts the U.S. a full decade behind the UK.

But my real complaint about the article was that it ignored the most significant findings of the study. The report emphasized that no matter which country you looked at – the UK or the U.S. – health status was highly correlated with income and status. People in the highest third of the income strata was significantly healthier than people in the bottom third.

I chose to cover this angle when I first reported the study, and it was the same angle that Paul Krugman emphasized in his column in the Times a few days later. For Kolata, though, the idea that the maldistribution of wealth and income might have something to do with health is simply idée non grata, even when it is prominently featured in the study on which she is opining.

As I long ago learned, when it comes to a Kolata story, let the reader beware.

FDA Woes

The following story appeared in this month's AARP Bulletin:

By Merrill Goozner
Last September an advisory panel voted 8-1 to recommend that the Food and Drug Administration approve a new drug for diabetes even though the risk of heart attack and stroke doubled among patients in clinical trials. The only cardiovascular expert on the committee didn't attend the panel's meeting because he had performed work for the drug manufacturer. But then, so had the committee's chairman, who did attend and in fact ran the meeting.

Some of the nation's leading cardiologists were upset by the recommendation. Writing in the Journal of the American Medical Association a few weeks later, they called on the FDA to reject muraglitazar because Bristol-Myers Squibb and Merck, its manufacturers, had failed to provide an accurate measure of the medication's risk.

"I'm increasingly concerned that these panels have become unbalanced," says Steven Nissen, M.D., of Ohio's Cleveland Clinic, a co-author of the JAMA article and former chair of the FDA's cardiovascular drugs advisory panel. "We have to make certain we have a balance of experts, [including] people who deal with the complications and side effects."

"There's too much bias toward bringing new treatments to market," adds Art Levin, director of the Center for Medical Consumers in New York and the consumer representative on the FDA Drug Safety and Risk Management Advisory Committee.

The FDA regulates companies that account for 25 percent of the U.S. economy. Its job is to protect the public from unsafe drugs, faulty medical devices and contaminated food. But 100 years after the birth of this federal agency, many doctors, consumer groups and lawmakers worry that the FDA is becoming less effective in carrying out its mission.

The hazy relationship between the FDA's advisory committees, such as the one for the diabetes drug, and the companies the agency regulates is just one issue raising concerns about the effectiveness of the FDA, which is still considered the gold standard among food and drug regulators around the world. Two other issues are a reported backlog of more than 800 generics awaiting approval and what the FDA acknowledges is the lax monitoring of drugs after they are approved and on the market.

"A lot of people are nervous about what's in their medicine cabinet, and for good reason," says Sen. Chuck Grassley, R-Iowa, a leading agency critic on Capitol Hill. "[The FDA] has become too cozy with the industry it regulates ... That's not a recipe for full trust and faith among consumers."

Acting FDA Commissioner Andrew von Eschenbach, M.D., the director of the National Cancer Institute who has been nominated to head the FDA permanently, insists the agency is working to protect the public. "We are making a tremendous commitment to the whole area of drug safety," he told Congress in March.

Serious questions about conflicts of interest at the FDA arose in 2004 when the painkiller Vioxx was taken off the market because it increased the risk of heart attack and stroke. Concerned that similar drugs might pose the same risk, the FDA convened a special advisory committee to evaluate the evidence. The agency almost always follows the advice of advisory panels, whose members are usually drawn from prominent medical institutions outside the FDA. Critics say most of the outside advisory panels include scientists with ties to the firms whose products are under agency review.

The panel that analyzed Vioxx, Celebrex and Bextra voted in February 2005 to keep them on the market, even though Vioxx had already been pulled. Only later did the media report that nearly a third of panel members had ties to makers of the drugs. Had their votes been excluded, the drugs would not have gotten a positive vote.

An FDA spokesman says advisory panelists are screened to "carefully weigh any potential financial interest with the need for essential scientific expertise" to protect public health.

"One of the conundrums," says Carl Peck, former director of the FDA's Center for Drug Evaluation who now heads the Center for Drug Development Science in Washington, is that the scientists "who are capable of making an informed decision are the very ones who typically are called on by drug companies and FDA to advise." He argues that limiting advisers to those who've never had research or consulting agreements with drugmakers could reduce the pool of qualified experts.

But Eric Topol, M.D., of Ohio's Case Western Reserve University disagrees. He says it's "essential for the 'jurors' to have no conflicts. There are many people who would qualify who have absolutely no ties to industry."

After the Vioxx decision, the FDA pledged to tighten its review process by creating an internal Drug Safety Oversight Board. The group has come under fire for meeting in secret, but the FDA says information from the companies involved is confidential. Peter Gross, M.D., outgoing head of the FDA's drug safety advisory committee, has urged more transparency, with "public representatives" named to the board.

The FDA gets more than 20 percent of its $2 billion annual budget from industry user fees, which are paid by companies seeking the FDA's OK to market new products. The fees, which account for nearly half of the new-drug office's budget, were mandated by law in 1992 to speed up the approval process by enabling the FDA to hire more reviewers.

"That's the problem," says Nissen of the Cleveland Clinic. "It would be smarter if we funded the FDA through public dollars. In terms of our national budget, it's trivial."

"I understand the importance of bringing new medications to market," he says. "But I just want to make sure we've appropriately balanced risk with benefit."

Meanwhile, just under 3 percent of agency funds is devoted to monitoring drug side effects. The FDA recently reported that drugmakers failed to begin two-thirds of post-approval studies it had requested. The agency has hired a consulting firm to assess the problem.

"The greatest flaw in our post-marketing system," Peck says, "is that it's voluntary by physicians and patients. This needs to be fixed."

He adds, "Everything needs improving, all the time."

The Ethics of Business-Run Clinical Trials

Assume for a moment that you are overweight and have high blood pressure. Before writing a prescription, your doctor asks if you would like to take part in a clinical trial for a new drug that holds out the promise of lowering blood pressure faster and more effectively than existing medications.

"Does it work," you'd probably ask. And your doctor would answer something like this: "I don't know. That's why we're doing the clinical trial. But don't worry, there is no placebo arm in this trial because we couldn't ethically deny you the standard of care since there are already so many blood pressure control medicines out there that we know work."

"So I will get either an existing, effective treatment or the existing treatment plus this new drug?"

"Yes."

"So what's the point? How will you know if it works?"

"Well, what we hope to learn is whether it works faster or better."

"Oh, I see. Sure. I'll take part."

Thousands of people sign up for clinical trials on these terms every day. It's especially true in cancer clinical trials, where desperately ill patients are anxious to get their hands on the next drug in the pipeline without giving up the not-very-good but better-than-nothing standard of care.

But let's change the scenario slightly. As a patient, what whould you do if you had very strong suspicion that the new drug was going to turn out better? Indeed, what would you do if you knew, in a statistical sense, that it was going to turn out better? Would you willingly go into a randomized clinical trial where you had a 50-50 chance of getting the old standard of care?

"If I'm 90 percent sure a new treatment will be better, would I be randomized to a 50-50-chance? Of course not," said Benjamin Djulbegovic, a professor of medicine at the University of South Florida, who has devoted his career to applying the mathematics uncertainty principle to clinical trial ethics. "Ethicists and scientists have said you shouldn't do trials where you have a good idea what the outcome will be. You'd be exposing people to inferior treatment, which is unethical."

Yet, based on an article that appeared in today's Journal of the American Medical Association, people do it every day when they enter industry-sponsored clinical trials.

The study compared the past five years' results from industry-sponsored clinical trials on various cardiovascular medicines and procedures to the results of similar trials sponsored by non-profit organizations like the government or foundations. The authors, Paul Ridker and Jose Torres of Brigham and Women's Hospital in Boston, limited their research to the three leading medical journals -- the New England Journal of Medicine, The Lancet and JAMA -- so they would only consider "high quality" studies.

The results were not surprising, since any number of previous studies have reached similar conclusions. Fully 67.2 percent of the industry-sponsored trials turned out to favor the new product or procedure over the standard of care compared to just 49 percent of the studies funded by non-profit entities.

The article contains a good discussion about the various biases that may have contributed to these results. But I want to focus on just one issue physicians should begin thinking about if they take its findings to heart: It is ethical to put a patient in an industry-funded trial?

The math, according to Djulbegovic, is unassailable. If a clinical trial is well-constructed, its architects won't know what the outcome will be. In statistics, this is known as the uncertainty principle and suggests that over time, and with enough examples, the distribution of answers to a binary question (is it better or is it worse) should hover around 50 percent on each side. And as we can see from the latest Ridker-Torres study, that's precisely what happened when they looked at 101 randomized clinical trials conducted by non-industry-funded scientists. These scientists were more likely to be asking questions and picking subjects for randomization in an unbiased manner, thus ensuring that the ultimate outcome was, at the outset, truly unknowable.

But that isn't what happened with 137 industry-funded trials in the study. With a two-thirds success rate, the odds were more like the House in Las Vegas than a coin-toss. "Incentives surrounding for-profit organizations have the potential to influence clinical trial outcomes," the authors wrote.

"There's all kinds of problems," said Djulbegovic. "If you select a comparator you know is inferior, you are violating the uncertainty principle. Then there's profit-driven me-too drugs and poorly designed trials. Plus they don't publish unfavorable results."

That latter factor actually works to drag the industry-funded trial ratio back toward the expected average. But scientists -- and patients and regulators -- never benefit from that knowledge because it doesn't enter the public domain.

The cure for this disease is to have independent scientists test new drugs and devices with all outcomes, whether positive or negative, made publicly available. If medical journals aren't interested in negative trials, then the results can at least be posted on websites and on the government's clinical trials database.

This shouldn't be an argument that hinges on what one thinks about "big business" or "the drug industry." Given the growing body of evidence about industry-funded clinical trial outcomes, it is an ethical imperative.

FAIR on Tom Friedman

I had lunch the other day with a friend who expressed amazement that I had not read Tom Friedman's book, "The World is Flat." I replied that I found most of his columns facile when they weren't boring, especially when dealing with the Middle East, which is supposedly his area of expertise. The Fairness and Accuracy in Reporting website has just documented his conventional wisdom on the war in Iraq, providing me with additional ammunition for combating those million-plus Friedman fans, which includes, alas, a number of my acquaintances and friends. Here is their analysis:

Tom Friedman's Flexible Deadlines Iraq's 'decisive' six months have lasted three and a half years

5/16/06

New York Times foreign affairs columnist Tom Friedman is considered by many of his media colleagues to be one of the wisest observers of international affairs. "You have a global brain, my friend," MSNBC host Chris Matthews once told Friedman (4/21/05). "You're amazing. You amaze me every time you write a book."

Such praise is not uncommon. Friedman's appeal seems to rest on his ability to discuss complex issues in the simplest possible terms. On a recent episode of MSNBC's Hardball (5/11/06), for example, Friedman boiled down the intricacies of the Iraq situation into a make-or-break deadline: "Well, I think that we're going to find out, Chris, in the next year to six months—probably sooner—whether a decent outcome is possible there, and I think we're going to have to just let this play out."

That confident prediction would seem a lot more insightful, however, if Friedman hadn't been making essentially the same forecast almost since the beginning of the Iraq War. A review of Friedman's punditry reveals a long series of similar do-or-die dates that never seem to get any closer.

"The next six months in Iraq—which will determine the prospects for democracy-building there—are the most important six months in U.S. foreign policy in a long, long time."
(New York Times, 11/30/03)

"What I absolutely don't understand is just at the moment when we finally have a UN-approved Iraqi-caretaker government made up of—I know a lot of these guys—reasonably decent people and more than reasonably decent people, everyone wants to declare it's over. I don't get it. It might be over in a week, it might be over in a month, it might be over in six months, but what's the rush? Can we let this play out, please?"
(NPR's Fresh Air, 6/3/04)

"What we're gonna find out, Bob, in the next six to nine months is whether we have liberated a country or uncorked a civil war."
(CBS's Face the Nation, 10/3/04)

"Improv time is over. This is crunch time. Iraq will be won or lost in the next few months. But it won't be won with high rhetoric. It will be won on the ground in a war over the last mile."
(New York Times, 11/28/04)

"I think we're in the end game now…. I think we're in a six-month window here where it's going to become very clear and this is all going to pre-empt I think the next congressional election—that's my own feeling— let alone the presidential one."
(NBC's Meet the Press, 9/25/05)

"Maybe the cynical Europeans were right. Maybe this neighborhood is just beyond transformation. That will become clear in the next few months as we see just what kind of minority the Sunnis in Iraq intend to be. If they come around, a decent outcome in Iraq is still possible, and we should stay to help build it. If they won't, then we are wasting our time."
(New York Times, 9/28/05)

"We've teed up this situation for Iraqis, and I think the next six months really are going to determine whether this country is going to collapse into three parts or more or whether it's going to come together."
(CBS's Face the Nation, 12/18/05)

"We're at the beginning of I think the decisive I would say six months in Iraq, OK, because I feel like this election—you know, I felt from the beginning Iraq was going to be ultimately, Charlie, what Iraqis make of it."
(PBS's Charlie Rose Show, 12/20/05)

"The only thing I am certain of is that in the wake of this election, Iraq will be what Iraqis make of it—and the next six months will tell us a lot. I remain guardedly hopeful."
(New York Times, 12/21/05)

"I think that we're going to know after six to nine months whether this project has any chance of succeeding. In which case, I think the American people as a whole will want to play it out or whether it really is a fool's errand."
(Oprah Winfrey Show, 1/23/06)

"I think we're in the end game there, in the next three to six months, Bob. We've got for the first time an Iraqi government elected on the basis of an Iraqi constitution. Either they're going to produce the kind of inclusive consensual government that we aspire to in the near term, in which case America will stick with it, or they're not, in which case I think the bottom's going to fall out."
(CBS, 1/31/06)

"I think we are in the end game. The next six to nine months are going to tell whether we can produce a decent outcome in Iraq."
(NBC's Today, 3/2/06)

"Can Iraqis get this government together? If they do, I think the American public will continue to want to support the effort there to try to produce a decent, stable Iraq. But if they don't, then I think the bottom is going to fall out of public support here for the whole Iraq endeavor. So one way or another, I think we're in the end game in the sense it's going to be decided in the next weeks or months whether there's an Iraq there worth investing in. And that is something only Iraqis can tell us."
(CNN, 4/23/06)

"Well, I think that we're going to find out, Chris, in the next year to six months—probably sooner—whether a decent outcome is possible there, and I think we're going to have to just let this play out."
(MSNBC's Hardball, 5/11/06).

Integrity in Science Watch -- May 15

FDA Conflict of Interest Ban Passes House Appropriations Committee

The powerful House Appropriations Committee has sent the full House a Food and Drug Administration spending bill that will prohibit the FDA from putting scientists with conflicts of interest on outside advisory panels. "Plain and simple, if a doctor or scientist has a personal, financial stake in a drug they should not be allowed to sit on an FDA advisory panel and determine whether that drug is safe," said Rep. Maurice Hinchey (D-NY), the chief sponsor of the amendment. A similar one-year measure passed the House last year, but was reduced in the Senate to a provision requiring the FDA to give 15 days advance notice before granting conflict-of-interest waivers. More than 100 conflict-of-interest waivers have been granted since the advance notice provision went into effect last October.

Half of Presenters at Main Oncology Conference Have No Conflicts of Interest

Food and Drug Administration officials who oppose a ban on placing conflicted scientists on advisory panels argue that most of the best people in any given field have some ties to industry and that it is extremely difficult to find experts without conflicts. But is that true? At the March 14th meeting of the Pediatrics subcommittee of the Oncology Drugs Advisory Committee, for instance, five of 12 panel members had their conflicts of interest waived so they could vote. Yet at the 2006 annual meeting of the American Society of Clinical Oncology, which takes place in Atlanta this June, nearly half of the 726 oncologists who will chair, speak or discuss their research do not have any conflicts of interest, according to the conference conflict-of-interest disclosure statement posted on the ASCO website. Only a third of the sessions will be chaired by physicians with ties to drug companies. The ASCO annual meeting, considered the "premier educational and scientific event in the oncology community," attracted more than 29,000 attendees last year. Meanwhile, under pressure to reform its advisory committee process, the FDA two weeks ago announced it would undertake a one-year study of its current system.

Unbalanced National Toxicology Program Extends Nomination Period

The National Institute of Environmental Health Sciences will consider public nominations for the scientific panel that oversees the National Toxicology Program (NTP), which reviews studies to determine which chemicals cause cancer and at what exposures. The terms of six scientists on the 16-member Board of Scientific Counselors, including two with close ties to regulated industries, expire next month. Three industry representatives -- Kenny Crump, principal at Environ International, an industry consulting company; George P. Daston, a research fellow at Procter & Gamble's Miami Valley Laboratories; and Keith Soper, a senior scientist at Merck - also sit on the committee.

Even though the Federal Advisory Committee Act requires that agencies balance outside advisory panels regarding points of view, scientists who work for or are closely aligned with environmental groups are currently absent from the NTP board. According to Barbara Shane and Mary Wolfe of the NTP Liaison and Scientific Review Office, NIEHS has not received qualified nominees from the public interest sector. "Scientific expertise is the most important thing," said Wolfe. NIEHS does not post announcements of openings on the NTP Board of Scientific Counselors in the Federal Register or on its website. It relies heavily on sending "notes" to former and current members and asking staff to research potential candidates. Shane said the NTP is accepting outside nominations for the six posts, which it hopes to fill by the end of this year.

Legislators Challenge NAS over Risk Assessment Panel

Four leading House Democrats have demanded the National Academy of Sciences ask tougher questions when it evaluates the White House proposal that adds another layer of peer review to agency risk assessments. Several federal agencies, including the Environmental Protection Agency, asked for the NAS review of the Office of Management and Budget (OMB) proposal, which will make it harder to approve new health, safety and environmental regulations. Rather than limit the NAS assessment to a scientific review, the House members asked the panel to evaluate whether the new risk assessment rules are even necessary; how they conflict with existing statutes; and what resources the agencies will need to be able to comply with an additional layer of peer review. The ranking members of the House Science, Energy and Commerce, Government Reform, and Transportation committees also asked the panel to evaluate "the potential for politicization of science" when "a White House policy office with little scientific expertise" evaluates science conducted at government agencies. Virtually every government agency that generates scientific documents to inform policy decisions already uses peer review, usually by external advisory committees.

The 18-member NAS panel that will evaluate the OMB peer review proposal is already under fire for waiving the agency's conflict of interest rules to include the principle of a major industry consulting group (see Integrity in Science Watch, April 24). In addition, staffers inside the EPA are questioning the conflict of interest of a key staffer who will help write the agency's response to the proposed rule, which is due June 12. According to Inside EPA (subscription required), Nancy Beck, who is now at EPA, helped draft the proposed risk assessment rule while at OMB. She was brought over to EPA to work on its response by George Gray, the politically-appointed chief of the EPA's Office of Research and Development. Gray joined the EPA from the industry-funded Harvard Center for Risk Analysis, where he co-wrote numerous academic articles on risk assessment with John Graham, who until recently was the top official at OMB dealing with regulatory affairs.

Cleveland Clinic Adopts Stronger Policy after Conflicts Exposed

Trustees, not physicians with ties to manufacturers, will take charge of how the renowned Cleveland Clinic invests a venture capital fund earmarked for new medical technologies, the Wall Street Journal reports (subscription required). Other changes include the creation of a database comprised of "companies with financial connections to trustees and staff" so that clinic purchases may be made appropriately, and a webpage that will list all of its physicians and their financial ties to industry. The revamped conflict-of-interest policy was adopted in the wake of revelations that hospital physicians, including chief executive Delos "Toby" Cosgrove, had conducted human research at the clinic on medical devices made by manufacturers with whom they had financial ties. "The active engagement of boards of trustees at health-care institutions in conflicts of interest is new," said David Rothman, the director of the Center on Medicine as a Profession at Columbia University. "The bottom line is this is encouraging."

The Lies That Keep On Running

Late last week, Merck unveiled the results of a study that purported to show that a one-year follow-up of the patients in the Vioxx trial that led to the drug being pulled from the market did not suffer from an increased risk of heart attacks and strokes after they stopped using the drug. Within 24 hours, the story had completely turned around: It turns out this was only true if you excluded some late arriving data, which added a number of strokes to the total and suggested that people who took Vioxx will remain at increased risk years after they've stopped taking the pill.

Then, this morning's Wall Street Journal carried a damning piece on the role of the New England Journal of Medicine in covering up its own role in failing to correct its original 2000 science article touting the virtues of Vioxx. It turns out last fall's "expression of concern," the first time the prestigious journal corrected the original article, was part of a public relations strategy to deflect attention from the fact that NEJM editors had been made aware that Merck scientists hid data in that original article, data that was submitted a few months later to the Food and Drug Administration and almost immediately brought to the attention of NEJM editors, who chose to ignore it.

Clearly, the courtroom drama surrounding Vioxx is spilling over into a recriminations battle among experts over who knew what and when. I highly recommend you go to the original sources if you're interested, and today's Wall Street Journal has all the links (pay the buck if you don't have an online subscription).

I have one major quibble with the article. It prominently quoted Dr. Gurkirpal Singh as a critic of Merck. When Singh last appeared in the press, he was working for Pfizer. And if you go back into the late 1990s, this minor academic was working for Merck and more than any other person was responsible for the myth that there was a major gastrointestinal side effect problem with traditional pain relievers that needed to be addressed by Cox-2 inhibitors like Vioxx and Celebrex. I wrote about this in my book, and I wrote about it again last year (see this GoozNews). But it seems that Dr. Singh's chameleon-like role in the long-running Vioxx saga is like the lie that travels a thousand miles before the truth even wakes up. He's still running strong. I keep waiting for an enterprising reporter to conduct a thorough post-mortem on his role in the Vioxx/Cox-2 affair.

Dems Win FDA Reform Measures in House

House Democrats led by Rosa DeLauro (D-Conn.) inched forward on another measure yesterday that would curb the power of the drug industry. Her amendment to the Food and Drug Administration appropriations bill would force drug companies to conduct post-marketing safety clinical trials ordered by the FDA or risk having the drug withdrawn from the market. Annual reports produced at the FDA show that about two-thirds of post-approval trials promised at the time of approval never get done.

This newfound power among House Democrats (yesterday, I reported that the same Appropriations committee passed Rep. Maurice Hinchey's amendment banning scientists with conflicts of interest from serving on FDA advisory panels) suggests that Big Pharma's rock-bottom public approval ratings, coupled with the sinking Republican poll numbers, adds up to declining clout on Capitol Hill -- a long overdue event.

Bill To Ban Conflicts of Interest on FDA Panels Moves Forward

Rep. Maurice Hinchey (D-NY) won passage late yesterday of legislation that would prohibit the Food and Drug Administration from placing scientist-physicians with ties to drug and device manufacturers on its advisory committees. Similar language passed last year, but got watered down in the Senate to an advanced notice reporting provision (which has been useful, but isn't as good as an outright ban which would open up these advisory process to the hundreds of medical thought leaders who conduct their research with government or foundation funds). You can read the Hinchey press release here.

Giving Credit Where Credit Is Due on Breast Cancer Coverage

When a reporter gets it right, they should be complimented. I didn't get around to reading the New York Times' Science section until tonight. But I was pleasantly surprised by Denise Grady's hardnosed story on drugs like tamoxifen and raloxifene (Evista) that reduce the risk of breast cancer. She carefully laid out the relatively low absolute risks most women face, which put these preventive pharmaceutical strategies in their proper context. We armchair journalism critics are quick to blame and don't often praise reporters when they get it right. She did. And it's a good read, too.

Who Knew About the Inexpensive Sleeping Pill?

We've all seen the ads for sleeping aides like Ambien and Lunesta. We've all heard the stories about the woman who woke up in the middle of the night, guzzled a bottle of wine and got arrested after urinating in the middle of a nearby intersection after taking one of the new pricey sleeping pills.

But who knew about the cheap generic pill (10 cents versus $3 for Ambien) that's been around since the 1950s and has almost no significant side effects? Not me, and I pay a lot of attention to these things (in part because I don't sleep much, but that's another story). An op-ed in today's New York Times by Daniel Carlat, the editor in chief of the Carlat Psychiatry Report, lays it all out.

The ostensible target of this op-ed (subscription required) was published review articles, paid for by Sepracor and Sanofi-Aventis, which make the two drugs, that sought to cast doubt on the efficacy of trazodone, the generic sleeping pill. His solution is to "mandate fuller disclosure of links between drug companies and authors" and require disclosure of "the exact nature of a doctor's involvement in preparing a sponsored article, as well as the dollar amount of his or her fee."

Now, I'm all for disclosure. But that hardly solves the problem. This is a classic example of the core fallacy behind "consumer-driven health care," which most conservatives see as key to holding down "waste" and "excessive spending" in our health care system. How will consumers learn about the trazodones of medicine when the entire weight of the health care complex's marketing machine is aimed at forcing compliant patients to demand and use the most expensive, and sometimes less effective, choice?

As the political season heats up, legislation to deal with the health care mess is popping up on Capitol Hill (medical malpractice bills -- again -- the non-answer to a non-problem; and insurance pools for small business are leading the pack). Meanwhile, numeous health care proposals are pouring out of the think tanks in Washington. From what I've seen so far, none are dealing with the core problems that are sending health care costs skyward without a concommitant improvement in the nation's health.

Health care may be a winning issue for the Democrats in the fall. But like the boost they'll get from public disaffection with the war in Iraq, rhetorical flourishes or two-bit tinkering are not substitutes for a program that will actually solve the mess. I think Americans are ready for some bold proposals. I'll review the various ideas floating around later this week. Got to run to work.

Integrity in Science Watch -- May 8

While NIH Docs Get Whistleblower Protection . . .

Highly paid government physicians now have access to the same whistleblower protection as other government employees, the Associated Press reports. The U.S. Merit Systems Protection Board reversed a previous government ruling that denied whistleblower protection status to Dr. Jonathan Fishbein, who was fired by the National Institutes of Health after revealing improprieties in a government-funded AIDS research program. Fishbein sued and was reinstated, although not in his old position.  Fishbein's lawyer hailed the latest Merit Board ruling. "Dr. Fishbein took a courageous stand in demanding full whistleblower protection in the face of a hostile federal bureaucracy," Stephen Kohn said. "Other Title 42 employees with information about wrongdoing can now blow the whistle and obtain protection."

. . . DOE Reassigns Nuclear Safety Official at Los Alamos

The Department of Energy has reassigned a top safety official at Los Alamos National Laboratory after he blew the whistle on the facility's history of safety violations. Christopher M. Steele was assigned to oversee national safety-training programs after he publicly reported numerous mishaps, including mishandling of radioactive materials, improper storage of plutonium and the rate of employee injuries at the New Mexico lab. Although the Department of Energy's National Nuclear Security Administration said they were promoting Steele to a position of higher authority, Steele said Energy Department officials have twice threatened to fire him for protesting safety conditions and feels his transfer will further jeopardize safety at the laboratory in Los Alamos.

While Gulf War Illness Grant To Sidestep Peer Review Process . . .

Sen. Kay Bailey Hutchison (R-Tx) has earmarked $75 million over five years for the University of Texas Southwestern Medical Center to investigate a disputed theory that neurotoxin exposures triggered the rash of debilitating illnesses among thousands of GIs returning from the First Gulf War. The earmark represents the "possibly first ever" instance where a Veterans Administration research program was funded without peer review, Science Magazine reports. While UT will fund a number of projects, the primary beneficiary of the grant will probably be epidemiologist Robert Haley, who has linked nerve gas and pesticide exposure to Gulf War illnesses (his early research was initially funded by Ross Perot and the Department of Defense). Yet a 2004 Institute of Medicine report rejected the evidence as "inadequate" and claimed attempts by other researchers to replicate Haley's work failed. A separate VA committee, run by an Arizona businessman, called for further research into the problem.  

. . . Peer Review System Failing at Many Top Scientific Journals

The integrity of the peer review system was called into question in a New York Times article last week. Journal editors have difficulty weeding out flawed or fraudulent research like Hwang Woo Suk's stem cell paper because the peer review process has been compromised by "economic pressures," "the desire to avoid displeasing the authors and the experts who review manuscripts," and the "fear that angry scientists will withhold the manuscripts that are the lifeline of the journals, putting them out of business," Lawrence K. Altman wrote in an analysis in the Times. Moreover, many peer reviewers are just that - scientists who are chosen to review the work of their own colleagues with whom they are often competing for funding and prestige. Financial pressures are most intense at medical journals, where editors risk losing drug industry advertising and reprint sales by rejecting studies. That sentiment was echoed by Richard Smith, the former editor of the British Medical Journal, who said reporting findings from large clinical trials involving their products presents editors with "a frighteningly stark conflict of interest" in deciding whether to publish such a study.

CRO Hired Troubled Docs for Antibiotic Safety Trial
 
The Wall Street Journal reports that a contract research organization hired by Sanofi-Aventis to run safety tests for a new antibiotic hired a physician who is now in prison for submitting fraudulent data and another who had his license suspended shortly after completing the trial. The drug Ketek (telithromycin) has been associated with 10 cases of severe liver damage. Pharmaceutical Product Development, Inc., which paid physicians $400 per patient enrolled in the trial, said it reported the problems to Aventis. Internal company documents obtained by the Journal show that Aventis knew about problems with the trial, but did not provide details to the Food and Drug Administration. The FDA approved the drug in 2004 in the wake of an Anti-Infective Drugs Advisory Committee meeting at which 6 of 12 voting members received conflict of interest waivers and two other members usually present at the meetings were recused because of ties to the drug's manufacturer.

Former FDA Official Blames Congress for Short-Changing Agency

A former associate commissioner of the Food and Drug Administration documents the decline of that once-great agency in an important op-ed in today's Washington Post. Critics have rightfully blasted the agency for becoming too close to the drug industry in recent years. But few point out a major cause of the problem: the FDA now relies on drug industry user fees for fully 25 percent of its overall revenue and nearly half of its budget for regulating new drugs and medical devices. How tough can you be when saying no might put funding for your job in jeopardy?

William Hubbard, who retired from the FDA last year, puts the blame squarely where it belongs: on Congress, which has consistently underfunded the agency, especially its regional inspection divisions.

For most of the FDA's 100-year history, presidents and congresses have recognized its importance to public health by giving it the resources and authority to respond to the rapid evolution in risks from the thousands of products it regulates. But for some years now, the agency's budget has remained essentially flat while major new responsibilities have been piled on. The results of this weakening of the agency are easy to document: Food inspections have dropped from a robust 50,000 in 1972 to about 5,000 today, meaning that U.S. food processors are inspected on average about every 10 years. The chance of a food product from overseas being inspected is infinitesimal. Most raw materials for our drugs come from foreign producers that are rarely inspected. The rate of quality-control failures found in manufacturing facilities by FDA inspectors has soared. Think your pacemaker, heart valve, microwave oven or morning vitamin was inspected? Dream on.

The Prescription Drug User Fee Act is up for renewal next year. The time is ripe for questioning the government's reliance on industry user fees to fund just the FDA functions industry wants, and not the ones the public needs.

Great Minds, etc.

Paul Krugman's column in today's New York Times (subscription required) carries an analysis of "Our Sick Society" that mirrors the my own analysis on Wednesday. Way to go Paul. Its a message the broader audience needs to hear.

FDA Official Allegedly Contradicts Earlier Stance on Plan B

Two years ago the chief of the Food and Drug Administartion's new drug division said he alone made the decision to override an advisory committee's recommendation that Plan B, the morning after birth control pill, be made available over-the-counter. According to the May 8, 2004 Washington Post:

In a teleconference yesterday, Steven Galson, acting director of the FDA's Center for Drug Evaluation and Research, said he made the decision in consultation with the FDA commissioner's office but without other outside input. "The decision I made had to do with looking at all the data and reading all the transcripts," said Galson, who was named deputy director of the FDA's drug evaluation office in 2002 after more than 10 years with other federal agencies. He said he was especially concerned about the lack of information about "the younger age group between 11 and 14, where we know there is a substantial amount of sexual activity."

Yesterday, the Center for Reproductive Rights, which has filed suit against the FDA and has access to depositions in the case, told FDA Webreview that Galson's sworn deposition contradicts his earlier statements. "From January 2005 on, the decision making regarding Plan B was solely within Crawford's office," a CRR spokeswoman said. "He withdrew authority from Galson and Woodcock and they were sort of cut out of that decision making, which is unusual and a major departure from the ways things are typically handled."

Galson and FDA deputy commissioner Janet Woodcock were deposed in the federal suit in late April. It would appear that the threat of perjury clarifies memory in a way that teleconferencing with journalists does not.

Next up to testify: Mark McClellan, the head of the Center for Medicare and Medicaid Services. Meanwhile, former FDA acting commissioner Lester Crawford is under criminal investigation, reportedly for hiding financial dealings while holding that office. This suit bears watching.

Better Health -- It Isn't What You Spend

Amid a spate of interesting stories the past 24 hours, the one that caught my eye was the study published in the Journal of the American Medical Association that reported that late middle-aged Americans -- no matter what their income or education -- are less healthy than their British counterparts. Indeed, the most startling statistic in the study showed that "individuals in the top of the education and income strata in the United States have comparable rates of diabetes and heart disease as those in the bottom of the income and education strata in England."

The British authors of the study (they were funded by the U.S. National Institutes of Health) went to great lengths to compare apples to apples. They excluded black and Hispanics from the U.S. cohorts of 55- to 64-year-old cohorts they sampled. At several points in their study, they controlled for confounding factors like smoking and obesity. The bottom line was that when you looked at comparable groups of middle-aged men and women in the two countries, Americans -- despite spending more than twice the amount of money per person on health care -- reported significantly more illness than their British counterparts.

How much?

/ / / U.S. / / /England

Diabetes ......12.5% / 6.1%
Hypertension.42.4% /33.8%
Heart Attacks. 5.4% / 4.0%
Cancer.......... 9.5% / 5.5%

What could possibly account for this? They dismiss smoking, since the Brits smoke more than Americans. Obesity is much higher in the U.S., they admit, but there's more heavy drinking in England. After doing some statistical manipulations, they concluded that "very little of the overall between-country differences in health conditions are due to differences in this subset of behavioral risk factors."

They also dismiss Americans lack of health insurance. Since only 2.6 percent of the top income group in the U.S. don't have health insurance, and their overall health was worse than the bottom third of earners in England, "health insurance cannot be the central reason for the better health outcomes."

"Much evidence points to the social determinants of health -- the circumstances in which people live and work," they concluded. "Low status is related to adverse conditions at work, in residential aras, and in general, to lack of empowerment -- all are plausible links between socio-economic status and disease."

The New York Times coverage of this story today completely ignored the data behind this angle, which was the study's main observation. If you divide the U.S. middle-aged population into thirds by income, you find that diabetes rates among the lowest third was 14.3 percent while it was just 9.5 percent in the highest third. Hypertension? 46 percent in the lowest income group compared to 37 percent in the highest income group. Only cancer didn't follow this pattern: 10 percent of higher income Americans experienced cancer compared to 8.9 percent in the low-income group.

However, ALL of those numbers exceeded the disease rates among the lowest income third of Great Britains.

So if social status is truly the ultimate driver in health, then it would appear that in America it is good to be in rich. But being rich in America makes you no better off than the worst off Brit -- at least when it comes to health. Could it be that guaranteed health care without concern about cost; a social safety net for the unemployed; a still functioning pension system; a more equal division of society's benefits, i.e., does living in a society that guarantees "social security" in its broadest sense lead to better health outcomes?

That's a question worth pondering as we think about "fixing" our broken health care system.

Integrity in Science Watch -- May 2

Ag Secretary Refuses to Fill Consumer Slot on Organics Board

The USDA announced it will not fill the consumer group position on the National Organic Standards Board (NOSB) that was left vacant by the resignation of the food industry lobbyist named to the slot in December of last year. Consumers Union (CU) and the Organic Consumers Association (OCA) had protested the appointment of Katrina Heinze, manager of global regulatory affairs for General Mills (owner of Cascadian Farm organic food company), who quit the Board at the end of February. At the NOSB's mid-April meeting, Secretary of Agriculture Mike Johanns said that he would not replace her until the next round of appointments, slated for this December.  The two consumer organizations' letter to Secretary Johanns in mid-January demanded that Heinze and Daniel Giacomini, a consultant to the organic dairy industry who was also appointed to a consumer position on the panel, step down. "These individuals may be appropriate to serve for industry-related slots on the NOSB, but it is misleading to have them represent the interests of consumers and the public interest," said Urvashi Rangan, the Eco-labeling Project Director at the Consumer's Union.  When asked why the consumer position would remain vacant for the remainder of the year, Valerie Francis, staff officer for the NOSB remarked, "It was the Secretary's decision to pick [Ms. Heinze] and he didn't want to pick anyone else."

The 15-member National Organic Standards Board was formed in 1992 to assist the Secretary of Agriculture in determining which foods merit the organic label. Consumer groups have criticized the USDA for refusing to enforce statutes requiring organic cows be raised on pasture instead of feed lots. This has allowed the two largest organic dairy labels, Horizon and Aurora, to produce most of their milk in a way that violates organic standards while enjoying organic market prices.

Conflicts of Interest Rife on FDA Panels; Ultimate Decisions Unaffected

A study in the Journal of the American Medical Association concluded that while nearly 30 percent of outside advisers on Food and Drug Administration committees had financial ties to drug or medical device companies, none of the final results of 221 committees examined over a three-year time span would have been altered if the votes of those with conflicts had been excluded. Despite the findings, Peter Lurie, the study's lead author and the deputy director of Public Citizen's Health Research Group, said, "I don't think it's acceptable to say we're willing to take any amount of conflict up to the point at which the overall outcome changes." Consulting conflicts were the most prevalent relationship to industry, with nineteen percent valued at over $10,000. While a fifth of the advisers had direct financial ties to the company sponsoring the new drug or device, only one percent recused themselves from voting.

The study proposed that the FDA provide advance notice of the waivers given to scientists with conflicts of interest who serve on FDA panels. Last year, Congress passed such a law, which is up for renewal this year. The study also called on the FDA to issue more recusals. Last week, the FDA's Cardiovascular and Renal Drugs Advisory Committee, which met to discuss a draft guidance for labeling antihypertensive drugs, excluded two scientists who had conducted relevant studies for industry. The Center for Science in the Public Interest's Integrity in Science project had protested their presence on the panel.

Leading Medical Journals Depend on Drug Industry Advertising

A policy forum article in the new Public Library of Science (PLoS) Medicine says medical journals should "just say no" to drug industry advertising after finding that 95 to 99 percent of ads in the Journal of the American Medical Association came from the pharmaceutical and medical device industries. The authors sampled issues published between 1996 and 2004. "By exclusively featuring advertisements for drugs and devices, medical journals implicitly endorse corporate promotion of the most profitable products," the authors, who hailed from the Georgetown University School of Medicine, said. "Advertisements and other financial arrangements with pharmaceutical companies compromise the objectivity of journals." Their recommendation? Journals should solicit ads from firms that want to sell luxury goods to their well-heeled readers.

FDA Stance on Medical Marijuana Draws Opposition on the Hill

Rep. Maurice Hinchey, (D-NY) and twenty-three House members wrote a letter last Thursday to Acting FDA Commissioner Andrew von Eschenbach protesting the agency's failure to provide scientific evidence for its statement that "[n]o sound scientific studies supported medical use of marijuana for treatment in the United States..."  The coalition claimed the announcement ignored the findings of a 1999 Institute of Medicine report showing the active chemicals in marijuana are beneficial in treating pain, nausea and other symptoms which often accompany long-term illness.  Rep. Hinchey, who will reintroduce his amendment preventing prosecution for those who are associated with the medical use of marijuana in certain states, said "We saw it with the agency's decision on the emergency contraceptive, Plan B, and we're seeing it again with medical marijuana: the FDA is making decisions based on politics instead of science."

My Grandchildren

Here's my Social Security:

This is my granddaughter Rachel. She's 5!

And this is Sarah. She just turned 2!

Love you kids!

Granddad

Breast Cancer and the Press

I spoke Sunday morning before the National Breast Cancer Coalition's annual advocacy conference in Washington, DC. Here's a truncated version of my remarks:

A few years ago, the Journal of the National Cancer Institute published a study about the role of the press in spreading misinformation about breast cancer. The authors surveyed all the articles that appeared in popular magazines over a year's time. They found that fully 84 percent of the women portrayed in the articles were younger than 50, and nearly half were under 40. Yet just 16 percent of breast cancer cases occur among women under 50, and just 3.6 percent under 40.

There's a reason why writers and editors run such coverage.

Continue reading "Breast Cancer and the Press"

Lebron Walked

Folks who followed Michael Jordan's rise to basketball prominence have no trouble recalling his breakthrough moment: It was his sideways-moving jump shot from the top of the key over Craig Ehlo that sank the Cleveland Cavaliers in game 5 of a first round NBA playoff series in 1987. This poster shot has taken on iconic status.

Tonight, Lebron James danced through the key to hit the winning shot in game 3 -- always the crucial game in a 7-game set tied 1-1 -- to lift the visiting Cleveland Cavaliers over the Washington Wizards. It was his 40th and 41st points of the night, the most ever by a visiting player in his first NBA playoff game on the road.

But I doubt you will ever see it on television, the way we see Jordan's shot over and over again. Why? James walked.

Terrorism Stats -- the bitter truth

This just out from Rep. Henry Waxman's (D-CA) office:

Rep. Waxman issued a Flash Report examining data released by the State Department and National Counterterrorism Center that shows that the number of reported global terrorism incidents has increased exponentially in the three years since the United States invaded Iraq--an increase of over 5,000% in the number of terrorist attacks and over 2,000% in the number of deaths in three years.

The Administration claims that the 2005 data is not comparable with data from previous years because the rise in attacks is due to increased surveillance and better methodology. These are the same arguments the Administration made in 2003, when attacks rose to a 20-year high, and in 2004, when the number of attacks tripled in a single year.

When preparing this year's report, the Administration consulted with global terrorism experts who recommended that the Administration release data that could be compared to previous years. Professor David Laitin of Stanford University recommended that if the Administration changed its methodology, it should "recalibrate" data from previous years so "we do not lose a sense of the time trends." Not only did the Administration reject this recommendation, but officials denied the recommendation was ever made.

In response to the Administration's actions, Rep. Waxman stated: "For the third year in a row, the Bush Administration is playing games with the numbers to hide the truth: global terrorism has skyrocketed since the invasion of Iraq."

Stem Cell Patent Woes

Researchers who need access to the Wisconsin stem cell lines (among the few the Bush Administration allows federally-funded researchers to use) are running into problems with the owners -- the Wisconsin Alumni Research Foundation (WARF).

WARF, which dates from the 1920s and is the nation's oldest university-based technology transfer organization, owns Dr. James Thomson's seminal patents on deriving stem cells from human embryos. WARF is charging academic researchers $5,000 and commercial firms $100,000 to use his original lines. Moreover, most medical technologies that use stem cells will have to license the WARF patents.

But, according to the latest Technology Review, WARF is placing onerous restrictions on its licensees:

The (WARF) license for the University of California, for example, permits scientists to use only a small number of embryonic stem cell lines. And the license granted to the Howard Hughes Medical Institute, a nonprofit medical research organization that funds scientists across the nation, prohibits scientists from accepting funding from or collaborating with commercial companies unless the company has a commercial license from WARF. (Some companies have chosen not to take a license because of the cost.) That could make it difficult for academics to partner with companies to develop their discoveries into products or therapies.

WARF denies it stands in the way of stem cell research, pointing to the scores of licenses issued to both firms and academic researchers.

FDA To Slightly Redraw Labeling Guideline

Food and Drug Administration officials said they will make some subtle shifts in their proposed labeling guidelines for blood pressure pills. But at this morning's meeting of the Cardiovascular and Renal Drugs Advisory Committee, they indicated the changes will not be enough to stop the drug industry from using the new guidelines to market pricier drugs as superior even though they probably have no greater benefit than generics.

Robert Temple, chief of the new drugs division at FDA, said the redrawn Guidance will be published in the federal register, which will give the public time to comment. So I'll wait until that document becomes public before reaching any firm conclusions.

But Temple asked several pointed questions this morning that suggested where he is going with this Guidance. He wanted to know who would do trials about specific outcomes for specific patient subgroups if the FDA didn't provide incentives for the pharmaceutical industry. Specifically, he mentioned the HOPE trial, which was funded in part by companies that make an ACE inhibitor, ramipril. That trial, published in 2000, showed ramipril improved kidney function in diabetics. What that trial didn't ask was whether other drugs, either in its class or other classes like diuretics, did the same thing.

So there you have the bottom line. Unless Temple and his colleagues in the cardiovascular drugs division of FDA make more significant changes than they seemed interested in this morning, the Guidance will allow drug companies like King Pharmaceuticals, whose two patents on rampiril don't run out until 2008 and 2012, to market their drugs as better for diabetics compared to other drugs, even if those other drugs A) are cheaper; and B) are likely to be just as effective for diabetics. Alas, no one will test diuretics in that population since there's not much profit to be made from drugs that cost pennies a day, so we'll never really know.

Conflict and Balance on Federal Advisory Committees

Peter Lurie, Sid Wolfe and colleagues at Public Citizen published a paper in the current Journal of the American Medical Association that found only a tenuous connection between Food and Drug Administration advisory committee decisions and their members' financial ties to drug companies whose products were up for approval.

No shock there. Anyone who has ever sat through one of those meetings knows that serious differences on the committees are rare no matter who sits on the panels. Having attended plenty of these meetings, I've come to recognize that the core problem isn't financial conflicts but the fact that most of these committees lack overall balance. They are almost always made up of clinicians who treat patients and/or conduct clinical trials. They are usually on the lookout for the next new and hopefully better drug or device for their patients. It's only natural.

What the committees usually don't include are epidemiologists skilled in ferreting out the responses of groups that do not fare particularly well on the new drug. Or they don't include safety experts who are on the lookout for problems that have only been hinted at in the limited trials conducted for new drug approvals.

The Federal Advisory Committee Act, which was passed in 1972, requires that these panels exclude scientists with conflicts of interest (although it allows for waivers in case a person's expertise is needed, which the FDA uses liberally). It also requires that the panels be balanced.

Historically, the FDA, along with most other agencies of the government and the National Academy of Sciences, have interpreted that latter requirement to mean inclusion of the range of experts needed to get the job done. At the FDA, that might mean including a bunch of clinicians who treat patients, a biostatistician who can interpret data, a consumer representative and an industry rep, who usually doesn't vote. But the Government Accountability Office, in a critical review of advisory committees published in 2004, said that the balance requirement also refers to opinions, especially when the subject being discussed is controversial.

At tomorrow's Cardiovascular and Renal Drugs Advisory Committee meeting, which will discuss labeling antihypertensive drugs (see this GoozNews for a rundown of the issues), I will raise this point with the FDA during the public session (I'll post my full comments in the afternoon). The real problem with this committee is its lack of balance.

Late this afternoon, FDA officials sent me an email indicating that the chairman of the committee, whom the Center for Science in the Public Interest exposed as having conducted clinical trials on hypertension drugs for Bayer Pharmaceuticals, will not take part in the meeting, nor will another scientist whose research for drug companies directly pertained to aspects of the labeling controversy. Yet the pared down roster still does not include any of the physicians who played key roles in conducting the best antihypertension research of the past decade (the so-called ALLHAT trial) or participated in writing the National Institutes of Health-funded clinical practice guidelines for physicians treating people with hypertension.

FDA advisory committees should not be confabs of the like-minded. They should be a forum where the best minds in a field can openly debate the pressing issues daily practitioners face. No matter what the committee decides tomorrow -- and I'm hopeful that despite the myriad conflicts of the members who remain that they will suggest significant changes to the FDA proposal -- the FDA needs to do some serious rethinking about how it chooses its outside advisers.

FDA Approves Pot! (the chemical version)

I let this pass last week, but I've been meaning to come back to it when I got a few spare moments (which inevitably come around 10:30 p.m. at night when I'm having a glass of red wine to help me get ready for Jon Stewart's Daily Show).

While a few of the newspaper accounts about the FDA statement on medical marijuana (in response to pressure from Capitol Hill) mentioned this fact, it bears repeating: the FDA has already approved the active ingredient in pot as a drug. Unimed's Marinol (dronabinol) is the chemical THC. It's been approved to combat AIDS wasting and as an anti-nausea agent for people on chemotherapy.

Hmmm. It gives you the munchies and settles your stomach. Sounds like pot to me.

A careful reading of the FDA-approved label (reprinted here), however, provides good reason for testing whether smoking dope may have advantages over using its chemical extract. The clinical trial proving it rebuilt appetites for people suffering from AIDS wasting showed that the effects of the pill version did not kick in until two weeks after the onset of therapy. In other words, there's a trade off. You get lung cancer-causing tars with the dope, but you get the munchies a lot quicker. That's a cost-benefit analysis suitable for FDA analysis.

If I were dying of AIDS or cancer, it would seem like a reasonable trade off to me. Indeed, I spent some time this year with a friend who smoked a lot of marijuana to reduce his need for heavy narcotics as he lay dying of pancreatic cancer. It gave his family many more positive moments together during his final months than would otherwise have been the case. I doubt that would have been the case had he been taking THC as an antiemetic.

Drug Safety -- What's Your Standard?

Tons of press coverage for this morning's Government Accountability Office report criticizing the Food and Drug Administration's safety system. Much of the critique hinged on three easily rectifiable problems: a lack of independence for the too small safety office (its paltry staff is currently housed within the new drug approval division); a lousy post-marketing monitoring system; and a lack of resources. In other words, the FDA cannot fix its own problems. Only Congress, which controls the purse strings and the agency's legislative authority, has that power.

Bottom line: If you're worried about drug safety, remember to vote this November.

I was intrigued by one comment, though, which was contained in the Washington Post coverage. Caroline Loew, senior vice president of the Pharmaceutical Research and Manufacturers of America (PhRMA, the industry trade group), defended the FDA's record by saying only 3 percent of all aproved drugs were later withdrawn for safety reasons.

Hmmm. What other industry is proud of a 3 percent defective rate? Automakers or electronics equipment manufacturers, who expect 6 sigma quality from their suppliers? (That's 3.4 errors per million or 3.4 ten-thousandths of a percent.) Your favorite local restaurant? (Hey, you can't shut us down. Only 3 percent of our customers got food poisoning last week). How about the kid who mows the lawn? Okay, if he gets 97 percent of the grass, I'm satisfied.

Integrity in Science Watch -- April 24

Heart-stopping Failure to Balance Cardiovascular Drugs Committee

The Center for Science in the Public Interest has called on the Food and Drug Administration to postpone the April 26 Cardiovascular and Renal Drugs Advisory Committee that has been called to consider controversial new labeling guidelines  for blood pressure control drugs. Fully three-fourths of the 12-member panel received conflict of interest waivers.

Physicians can choose from at least seven classes of drugs to treat the 65 million Americans with hypertension, which is often caused by obesity, excessive salt consumption, and lack of exercise and is a major contributor to heart disease. Many of the 35 million Americans on antihypertensives take more than one drug. Drug labels - and the permissive statements those labels allow drug salespersons to make to physicians - can have a major impact on prescribing patterns.

Guidelines developed by the National Institutes of Health in 2003 suggested cheap, generic diuretics, which have been around since the 1950s, "have been virtually unsurpassed in preventing the cardiovascular complications of hypertension." Those guidelines, which, if followed, could save consumers, insurance companies and the Center for Medicare and Medicaid Services billions of dollars, also state that "diuretics should be used as initial therapy for most patients with hypertension, either alone or in combination with one of the other classes." The guidelines specifically recommend against using calcium channel blockers (Pfizer's Norvasc, a calcium channel blocker, is the world's best-selling anti-hypertensive drug) in patients with congestive heart failure.

The FDA's proposed label, on the other hand, states only that "numerous drugs from a variety of pharmacologic classes, whose only common property is to reduce blood pressure, have been shown to reduce cardiovascular morbidity and mortality." The accompanying discussion does not include congestive heart failure among its primary heart disease endpoints. "This document is written so industry can go out and say that it doesn't matter which drug you use," said Curt Furberg, a hypertension expert at Wake Forest University who sits on the FDA's Drug Safety committee. He wasn't invited to be part of this panel.

Several of the physicians who will play key roles in the committee's deliberations have conflicts of interest that relate directly to the labeling discussion. For instance, committee chair William R. Hiatt, a professor of medicine at the University of Colorado, has conducted research for Bayer Pharmaceutical showing the benefits of controlling blood pressure in diabetics with peripheral arterial disease. The label guidelines suggest secondary benefits like improved PAD can be used as a basis for recommending one drug over another. None of the 11 physicians associated with the National High Blood Pressure Education Program Coordinating Committee, which wrote the 2003 peer-reviewed guidelines, was chosen for the FDA panel.

The CSPI letter to acting commissioner Andrew von Eschenbach called on the FDA to balance the panel with experts familiar with the 2003 guidelines and experts on dietary approaches to controlling blood pressure. The group also recommended adding language to antihypertensive drug labels reminding consumers and physicians that "weight loss, diets rich in vegetables and fruits, and diets low in salt are simple ways of treating high blood pressure.  Lowering your blood pressure through such changes could save you the cost and side effects of this (and possibly other) medications."  

Industry-funded Docs Define Mental Disorders

Nearly a third of the physicians and psychiatrists who define mental illness for the medical profession had undisclosed financial ties to at least one pharmaceutical company, a new study released last week showed. And panels that defined severe disorders like schizophrenia in the Diagnostic and Statistical Manual of Mental Disorders (DSM) were entirely made up of members financially affiliated with drug companies. The manual is used by the almost one-half million mental health professionals in the U.S. Sheldon Krimsky of Tufts University, who co-authored the study in the Journal of Psychotherapy and Psychosomatics, concluded that the investigation "demonstrates that there are strong financial ties between the industry and those who are responsible for developing and modifying the diagnostic criteria for mental illness."  The authors call for transparency for future DSM panel members.  

Allergy Journal Strengthens Conflicts of Interest Disclosure Policy

The Journal of Allergy and Clinical Immunology (JACI), an Elsevier publication, will require greater financial disclosure from authors and automatically publish those disclosures, the editor said. Two mold experts, Dr. Abba Terr and Dr. Andrew Saxon, failed to disclose their roles as defense witnesses in mold exposure liability lawsuits when publishing a review in the journal earlier this year that downplayed the risks from household mold exposure. Editor Donald Leung said future author conflict of interest forms accompanying JACI submissions will now include "specific questions" about expert witnessing and the journal will "ensure that all published manuscripts will carry a conflict of interest statement regarding each author."

Industry Consultant on NAS Panel Reviewing OMB Risk Rules

Claiming the agency was unable to find another qualified candidate, the National Academy of Sciences has included one of the founders of ENVIRON International, a prominent industry consulting firm, on a new panel that will evaluate the Office of Management and Budget's proposed risk assessment guide released in January. Six federal agencies including the Environmental Protection Agency have asked the NAS to review the OMB proposal, whose time-consuming data review requirements would make it far more difficult to approve new health and safety regulations. The NAS waiver went to ENVIRON founder Joseph V. Rodricks, who is one of the eighteen members on the committee. NAS is "unable to find another individual with the equivalent combination of scientific credentials and expertise," the waiver stated.

Transcript Shows Bias in CDC Vaccine Study, Parent Group Alleges

Advocates for Children's Health Affected by Mercury has released a transcript of a conversation between the chair of an Institute of Medicine (IOM) study on the side-effects of vaccines and the study director at the IOM that suggests the study's outcome was predetermined. A Medscape article reported the transcript, which was posted on an activist group's website earlier this month. It includes a statement by Dr. Marie McCormick, Harvard researcher who chaired the IOM committee, to IOM's Kathleen Stratton that "we are not ever going to come down that [autism] is a true side effect." CDC spokesman Tom Skinner said the emails had been taken out of context. The agency takes its scientific credibility very seriously and "in no way" tried to influence IOM experts, he said.

Industry-Funded Scientists Spin Aspirin Debate

A Wall Street Journal article today describes the hidden financial ties between big drug companies and researchers involved a debate over "aspirin resistance."  Aspirin, the anti-clotting drug taken by millions of Americans, has been shown to help reduce the risk of heart attack and stroke by as much as 25 percent. An article published in Physician's Weekly last July by Daniel Simon, associate professor at Harvard Medical school, stated that as many as 30 percent of the 25 million aspirin-taking Americans were aspirin resistant, at higher risk for heart attacks and strokes, and may need other anticlotting drugs. According to the Journal, "the article didn't mention that Dr. Simon receives research funding from Accumetrics Inc., a privately held San Diego company that makes a test to measure aspirin resistance, and from pharmaceuticals maker Schering-Plough Corp., which sells a drug being tested as a potential benefit for patients deemed aspirin-resistant." Physician's Weekly managing editor Keith D'Oria said he knew about Simon's role with Accumetrics, but the weekly does not tell its readers about contributors' conflicts of interest.

The article also discloses that Dr. Eric Topol, a booster of the aspirin-resistance hypothesis who is now at Case Western Reserve University, consulted for Accumetrics and advised another aspirin resistance-testing firm, Aspirin Works, a division of Creative Clinical Concepts Inc. of Denver. He previously served as a consultant to companies that make aspirin alternatives including Bristol-Myers, Sanofi-Aventis and Eli Lily & Co.  Topol told the New York Times last year that he has since cut his ties to drug manufacturers.

It's Enough To Give You High Blood Pressure

Is it possible that a federal agency can, in the name of improving public health, make a decision that will not only make things worse, but cost consumers billions of dollars in the process? Not only is it possible, you can watch it happen next week by tuning into a Food and Drug Administration advisory committee meeting that will consider how drug companies label blood pressure control pills.

First some background. Fighting high blood pressure is big business. Over 65 million Americans suffer from hypertension. Well over half of them are already on medication, most on more than one drug. Pricetag? Well over $15 billion. And with the 77 million Baby Boomers heading into their high blood pressure years, the sky is the limit.

Continue reading "It's Enough To Give You High Blood Pressure"