Wednesday, February 25, 2009

Hot off the Press: US Investigating Forest Labs for Illicit Promotion of Kids' Antidepressants

As you have no doubt discerned, this blog is not exactly CNN-- you ordinarily do not turn here for the very latest news. However, thanks to alert e-mail correspondents and friends of our blog, I am able to shoot this out to you pretty quickly:

http://www.usdoj.gov/opa/pr/2009/February/09-civ-163.html

The Feds are investigating Forest Laboratories for illicit promotion of their antidepressant drugs Celexa and Lexapro. The basic charge is that the company funded a study in which it was shown that these drugs did not help kids with depression, and actually increased the suicide rate. [CORRECTION ADDED 2/26: Sorry, rushed this too fast yesterday. The actual study results did not show increased completed suicides but rather increased suicide ideation and attempts.] The FDA decided on the basis of this study not to approve the drug for use in children. But, as too often happens, the FDA then apparently did nothing to force release of these data. The company then concealed the data and aggressively marketed the drug for off-label use in pediatrics, using a full court press of the usual monetary bribes (speaker fees, consulting fees, lavish meals, etc.). Eventually the study led the FDA to demand a black box warning on the drugs regarding pediatric risks. The company's behavior came to light as a result of whistleblowers, according to the federal complaint.

Move Over, Zyprexa, Here Comes Seroquel

Y'all mosey on over to Danny Carlat's psychiatry blog--

http://carlatpsychiatry.blogspot.com/2009/02/of-seroquel-sex-and-secret-documents.html

--and read about the new scandal brewing about another "second generation" antipsychotic, Seroquel (quetiapine, manufactured by AstraZeneca). A class action lawsuit against the manufacturer for suppressing data on the medication's risks has created a trove of documents, and there are now calls to make them public, though as no trial has yet occurred the company is not legally obligated to do so. The whole matter is basically a reprise of the Lilly/Zyprexa case (see most recent post, http://brodyhooked.blogspot.com/2009/01/nice-article-on-zyprexa-debacle.html). Basic story line: drug is approved for psychosis (schizophrenia and bipolar disorder); company tries like heck to get it approved for marketing for more common disorders such as garden-variety depression and insomnia; lots of off-label prescribing ensues; a bunch of patients end up with severe obesity and diabetes.

For those interested in such things, there is also a sex angle to the AstraZeneca scandal, an element thankfully missing from the Lilly/Zyprexa case (at least so far as I am aware).

Saturday, February 21, 2009

Lilly Says Jump, FDA Says How High--More on "Intellectual Bias"

The main story appears on the "Heartwire" (theheart.org) site (and thanks to colleagues at Healthy Skepticism for the tip)--

http://www.theheart.org/article/943511.do

The story has several themes--most notably 1) the debate over "intellectual bias" or sometimes "intellectual conflict of interest"; and 2) the FDA's excessive willingness to do the bidding of industry and to neglect its duties to protect public safety.

The basic facts: The drug plasugrel, an anti-clotting drug supposedly of value in heart attack and stroke, is currently under review by an FDA scientific advisory committee. Dr. Sanjay Kaul, of Cedars-Sinai Medical Center in Los Angeles, had been invited to be a member of the advisory committee, but he was then asked by FDA staff not to make the trip to Bethesda. It was then revealed that Eli Lilly, the drug's manufacturer, had contacted the FDA just before the decision was made, to protest Dr. Kaul's earlier skeptical publications about the drug and his purported "intellectual bias." The FDA has now admitted error in this process.

Taking the latter theme first, there have been a number of instances in which physician-scientists who were known to be critical of a drug were excluded from an FDA advisory committee, even as scientists who had stark financial conflicts of interest with the manufacturer were allowed to sit on the panel through routine waivers of FDA rules. This, to the best of my recollection (which is exceedingly shaky these days), is the first time that there has been such a direct link made between a contact to the FDA by the company, and the decision to exclude the scientist. (Wouldn't want to keep the busy folks at Lilly waiting, after all.)

Now for the first theme. I have previously posted about this nonsense of "intellectual bias," which is not really so bad when called by that name, but does nefarious work when relabeled as "intellectual conflict of interest." See for instance http://brodyhooked.blogspot.com/2008/03/more-on-intellectual-conflict-of.html for a great expose of the flawed reasoning. The basic idea: Everyone agrees that scientists are subject to intellectual bias. They tend to believe that their own pet theories are right and the opposing theories are wrong. Apologists for industry then proceed to relabel this bias as "intellectual conflict of interest." They then proceed to argue that we should simply ignore financial conflicts of interest as unimportant. After all, they then argue, if COI is all over the place, we can hardly get too excited about any one manifestation of it; intellectual COI is all over the place; therefore we should not get excited about COI; therefore financial COI is not anything to worry about either. In other words, by this sleight of hand, we go from humans are human and have biases, to it is all right for scientists to pocket huge sums from manufacturers and then sit on FDA advisory committees judging that manufacturers' drug.

The FDA has, in recent years, promised to start to become tighter about enforcing their rules and not issuing blanket waivers like they used to. I am not sure how well they have made this switch in policy (anyone else know the recent track record?). What they clearly have done, however, is to be much stricter about letting the supposedly anti-drug folks sit on committees, even those who have no financial conflicts whatever and simply doubt the quality or validity of the drug industry's so-called evidence.

We can be hopeful that the Obama folks, when they finally come in and take over the FDA, may reverse these unfortunate trends, but we can also be sure that the industry is exerting its utmost behind the scenes to make sure that the harshest critics of industry do not make the final cut for high-level appointments in the Obama FDA.

Monday, February 16, 2009

Big Goverment Wants to Get Between You and Your Doctor: An Old Scare Tactic is Abroad in the Land

Somebody apparently feels that there's a real chance that the present administration might pass substantial health reform.

That would seem to be the implications of a couple of recent news items. The items show that conservative opponents of health reform (including, in this case, the champions of Big Pharma) have opened up a dusty old coffin to release the zombie that was highly effective at scaring the townsfolk in the past, and they obviously hope the ol' guy will do the trick one more time. The scary zombie is the threat that Big Government Wants to Get Between You and Your Physician.

Back off a bit for the big picture: As documented in HOOKED and on this blog, more than 80 percent of today's clinical trials of pharmaceuticals are company-sponsored. That means there are precious few head-to-head trials comparing rival drugs to see which is better. No company as a rule will take the risk that its own product will come in second. So most policy experts have said we will never control health costs in the US sufficiently to make care affordable for all who need it until we set up some sort of neutral agency to perform these needed head-to-head trials. Add to the lack of those trials the observation, well documented by Shannon Brownlee in her book Overtreated, that as much as a third of the US health care budget is spent on "treatment" that is actually useless from the patient's viewpoint. There's a lot of room to trim those costs without coming anywhere close to harming patients' vital interests. The sensible doc, far from seeing well-conducted efficacy trials as an interference with prescribing, desperately wants that scientific information as a tool to better serve patients.

Now, President Obama has done two things that are highly scandalous according to most Republicans. First, he says that in a time of threatened economic depression, federal spending might be needed to get the economy back on track and create new jobs. Next, he had the nerve to suggest that since we are going to spend Federal dollars to create new jobs, we might as well create those jobs doing something that we really need in the future. Since he's for health care reform, and knows that down the road sensible reform will require an agency to conduct serious efficacy trials of what works and what doesn't, he suggested putting some money into the stimulus package to fund that sort of health research.

This got the Republicans all upset, according to Dr. Doug Bremner's "Before You Take That Pill" blog:

http://www.beforeyoutakethatpill.com/index.php/2009/02/16/republicans-try-to-block-audacious-move-to-inform-healthcare-treatments-based-on-the-evidence/

Clearly, say the Republicans, a dastardly plot to put Big Government between you and your doctor. Meanwhile, over on the Columbia Journalism Review blog, Trudy Lieberman caught CNN doing a bit of Republican lobbying under the guise of news reporting:

http://www.cjr.org/campaign_desk/dart_to_cnn.php?page=all

She noted that Betsy McCaughey was quoted issuing dark predictions that under the new Obama health plan, the Feds would be issuing marching orders to your doctor, telling her what treatments to use. Asked what specific portions of the bill gave the Feds that authority, no one could say, but they concluded that because the language was vague, anything could happen. CNN conveniently left out the fact that McCaughey, a former New York lieutenant governor, had in past days attacked the Clinton plan with two articles in the New Republic [corrected 2/18: earlier text erroneously said the New Yorker--Sorry!] which were so full of factual errors that the magazine later had to retract them and apologize.

So-- be prepared to hear from a number of quarters in future months that big government wants to order your doctor how to treat you. When you hear that, you'll know that the apologists for the big drug companies, the big insurance companies, and all those who make a killing off the present inefficiencies in our so-called health system are on the prowl.

Friday, February 13, 2009

Ninety-four Percent of Industry Cancer Trials Not Published?

Thanks to my friends Rick Bukata and Jerry Hoffman and their "Primary Care Medical Abstracts" for calling my attention to this paper.

Ramsey and Scoggins of the Fred Hutchinson Cancer Center in Seattle asked a simple question--if you look for clinical trials of cancer treatments (almost all of which are drug therapies) on the major trials registry, ClinicalTrials.gov, and then look to see if they were published in a journal indexed by PubMed, how many show up? They did a download of eligible trials from the registry in September, 2007 and checked out PubMed in November of the same year.

One thing they found was that 21% of trials registered three years or more previously had been published while only 11.9% of more recent trials had been. So if they had waited longer, they might well have found a higher number of trials published.

The next thing they found was that overall, only 17.6% of trials had been published. So even if waiting longer had caused this number to double, that's still an awful lot of data that is not being captured by the published literature.

The point I want to focus on is the breakdown by type of sponsor. While no one was terrific given the 17.6 % overall publication percentage, the worst statistics were for industry sponsored trials, with only 5.9% being published. Moreover, 64.5% of all trials that were published were reported to have been positive, suggesting as one would expect a substantial publication bias toward positive studies. Of the industry sponsored studies, fully 75% that were published were positive.

Conclusion: An industry sponsored trial that is negative is far more likely never to be published than a negative study of another sponsor's; and the total number of studies conducted by industry that remain unpublished in the cancer area is staggering.

Of course, if a study turns out to be flawed, or never enrolls enough subjects, or fails for many other possible reasons, then there are justifications for why it may never be published. The problem is imagining that these bad things happen selectively to industry-funded trials--especially when the industry, as I documented in HOOKED and on the blog, devotes considerable funds and efforts to asssuring that these unfortunate things do not happen to their trials.

The authors are concerned more with the way that oncology is forced to depend on a very biased and incomplete literature, than they are with industry-sponsored studies specifically. And that concern is obviously a highly legitimate concern. Nonetheless this study provides substantial statistical backup for a phenomenon that we had feared all along was occurring--systematic suppression of negative studies by industry.

Ramsey S, Scoggins J. Commentary: practicing on the tip of an information iceberg? Evidence of underpublication of registered clinical trials in oncology. The Oncologist 13:925-929, 2008.

Thursday, February 12, 2009

Family Doc President Opposes Present Federal Sunshine Provisions

This blog requires my best efforts to be even-handed. (Yes, I know that that statement will seem like a big joke to some readers.) So I have to devote equal time to beating up my own specialty of family medicine, as I have done with psychiatry and other recent targets.

This week's news from the American Academy of Family Physicians informs members that our President, Dr. Ted Epperly of Idaho, has taken issue with some of the provisions in the Physician Payments Sunshine Act introduced by Sens. Grassley and Kohl:

http://www.aafp.org/online/en/home/publications/news/news-now/professional-issues/20090209sunshine-act.html

Some of my family medicine colleagues who share my views about ethics and the pharmaceutical industry lit into Dr. Epperly with all barrels blazing, so it's only fair to quote that "he agrees with the overall intent of the Physician Payments Sunshine Act of 2009...[and says,] 'We need to have transparency' between physicians and the pharmaceutical industry and device manufacturers... However, the latest version of the bill is overly onerous and creates the potential for
'unanticipated and unintended consequences.' "

Nevertheless, while Dr. Epperly seems to be claiming that he's merely trying to fine-tune the bill, his specific proposals sound more like drug industry lobbying than like the statement of a president of a professional society. He is worried that individual family physicians will be overly burdened by the reporting requirements for amounts as low as $100 (when the real burden for reporting falls on the industry, not the physician). He is worried that physicians will be deterred from gaining needed continuing education (when the AAFP should be encouraging their members to get CME from sources that are not commercially tainted).

I was forced to disclose in HOOKED that the AAFP, at least several years ago when I had access to the data, received roughly a third of its operating revenue from the pharmaceutical industry. Dr. Epperly's comments highlight the concerns that we have when professional societies become that dependent upon industry funds--it seems very easy to assume that the interests of the professional medical organization are identical with those of the industry that foots so much of the bill. And that, in turn, is a very worrisome state of affairs. AAFP should think more about getting its own house in order (as some of its own state chapters have done by declaring their annual state-wide meetings pharm-free) and less about telling Senators Grassley and Kohl what to put in their bill.

Wednesday, February 11, 2009

More on Out-of-Control Prices for Cancer Drugs

I recently (http://brodyhooked.blogspot.com/2009/01/compassion-or-conflict-of-interest-new.html) posted about Medicare rules changes that will encourage more spending on cancer drugs of questionable value, by including as officially recognized "compendia" drug lists that are compiled by groups with blatant financial conflicts of interest. The New York Times editorially recognized the problem:

http://www.nytimes.com/2009/02/10/opinion/10tue2.html?_r=1

The editorial is based both on press coverage of the new Medicare rule on drug compendia for off-label use of cancer drugs, and also on an important recent policy study in the New England Journal of Medicine by Peter B. Bach of Memorial Sloan-Kettering Cancer Center in New York. Bach lists the various ways Medicare controls the costs of other drug treatments, and then proceeds to show how specific provisions in Medicare laws and regulations prevent the program from using those same means on cancer drugs. The end result is a major recent increase in the costs of cancer treatment. There have been major breakthroughs in the survival rates for a few specific tumors, a modest improvement in survival rate for other cancers, and finally the development of chemotherapy agents that have significantly reduced side effects compared to older drugs. Bach, however, is of the opinion that the increase in prices far outstrips any increase in efficacy.

The New York Times editorial suggests that the answer will be found in government programs to compare drugs head-to-head to determine their true efficacy and cost-effectiveness. Bach endorses this approach, and also pilot programs to test prospective payment mechanisms. (The latter being one more sign that policy wonks, at least, are starting to regard the much-maligned HMOs and managed care programs of the 1990s as the good old days of keeping medical costs under control while providing a generally decent level of care.)

Bach PB. Limits on Medicare's ability to control rising spending on cancer drugs. New England Journal of Medicine 360:626-633, February 5, 2009.

Sunday, February 8, 2009

Royal College of Physicians Report: Little New Here

The Royal College of Physicians of London have issued a report, Innovating for Health, on the relations between medicine and the pharmaceutical industry:

http://www.rcplondon.ac.uk/news/news.asp?PR_id=435

The 7 February issue of the BMJ has a number of commentaries:

http://www.bmj.com/cgi/content/full/338/feb05_1/b463

At first blush, the report appears to be a hard-hitting document that calls for a radical restructuring of the relationship, with a special focus on the industry divesting from all professional education activities, and that argues that the public has lost faith in the present prescribing process. However, Joe Collier, an emeritus professor of policy at St. George's, London, expresses disappointment in his BMJ editorial (http://www.bmj.com/cgi/content/full/338/feb03_2/b443) that the RCP working group seemed to lean over backwards to improve the image of the drug industry. He claims that the industry took a huge PR hit in a 2005 report from the House of Commons Health Committee (noted in HOOKED), and the RCP seemed to believe that the record needed to be set straight on that. Still he agrees with a number of the specific recommendations in the report.

The focus of the report is "innovation." The Executive Summary calls for moving beyond "past confrontational debates" to decide upon a national policy for the UK, involving public, private and professional sectors, to restore innovation in medicines to a higher priority status. There is little evidence, however, that innovation has somehow been stifled by the actions of the government and the profession. It seems far more plausible to argue that the major cause of a lack of innovation has been the R&D and marketing decisions of the industry--that it had much more to gain by rediscovering me-too drugs for lifestyle conditions rather than developing new types of drugs that met serious public health needs.

The bottom line seems to be that for regular readers of this blog there is little real news in the RCP report. (Note: The Executive Summary is available on line but the full report, some 70 pages, is available only to RCP members.)

Monday, February 2, 2009

When Medical Societies Become Lobbyists for Big Pharma

Working backwards on this one, I first had it from Roy Poses' "Health Care Renewal" blog that referred me to a blog by Alison Bass:

http://alison-bass.blogspot.com/2009/01/connect-dots-between-medical-groups-and.html

Which in turn quoted the Boston Globe:

http://www.boston.com/news/local/massachusetts/articles/2009/01/24/new_drug_firm_limits_prompt_fears_of_falloff_in_medical_meetings_in_city?mode=PF

Here's the quick scoop--Massachusetts recently, as part of its efforts to cut health care costs to accommodate its new health reform law mandating insurance coverage for most residents, passed a strict law limiting financial relationships between drug companies and medical activities. Though the final rules have not yet been put in place, three medical professional societies have announced plans to switch their major CME meetings out of Boston, claiming that the new law will unduly restrict presentations given by drug company scientists. The organizations are the American Academy of Allergy, Asthma and Immunology, the American Society for Gene Therapy, and the Heart Rhythm Society.

Defenders of the new law say that there will actually be no such restrictions on which scientists can speak at meeting and that the move amounts to fear-mongering on the part of the societies. Bass goes beyond the Globe article by pointing out who bankrolls the three societies, and notes that major bioetech and pharma interests that were opposed to the new law are heavy funders.

So now we have the spectacle, not only of supposedly "professional" medical societies taking lots of dough from industry regardless of the conflicts of interest that this poses, but of the societies then proceeding to carry the lobbying water for those companies, making the industry's cause their own. A pretty sorry statement for "professional" advocacy and ethics.