More on Strict Measures Proposed in India

Pharmascolds in the U.S. are celebrating the passage of the Physician Payment Sunshine Law, which (viewed cynically) allows all docs to take as much money as they want from Pharma, only they have to disclose it. It is breathtaking to see how far the U.S. scene lags behind India if this news account is indicative (open source; hat tip to Healthy Skepticism listserv for making me aware of it):

http://www.pharmabiz.com/article/detnews.asp?articleid=54670&sectionid=
MCI asks Health Ministry to make pharma cos punishable for gifting docs
Thursday, March 25, 2010 08:00 IST Ramesh Shankar, Mumbai
The Medical Council of India (MCI) has asked the Union Health Ministry to amend the Drugs and Cosmetics Act to bring the pharmaceutical companies under the ambit of the law in making them punishable for rolling out freebies to the doctors for promoting their medicines. At present, only the doctors who accept gifts from companies will invite action by the MCI, and the pharma companies who roll out the gifts are out of the purview of the law.
MCI chairman Dr Ketan Desai said that the MCI has written a letter to the union health ministry in this regard. He said the MCI has suggested the cancellation of licenses of such pharma companies who are found to be involved in unethical trade practices.
Coming close on the heels of its recent notification under which the doctors who accept any kind of gifts from pharma companies will invite cancellation of their registration to practice, the MCI's new initiative will bring the pharma companies under the law in which they will be punished if found guilty of giving any kind of gift to the doctors as part of their promotional activity. The pharma companies very often extend several kinds of gifts to the doctors including domestic and foreign holiday packages to promote their products. The MCI's initiative to make the pharma companies also legally bound to follow the ethical trade practices comes in the wake of media reports that several pharma companies are still openly floundering norms to offer gifts to the doctors to promote their medicines. Recently there were reports in the media that prominent pharma companies like Dr Reddy's and Piramal had resorted to unethical trade practices. While, Piramal had taken a group of doctors to Turkey, Dr Reddy's had taken the doctors to Hyderabad for some seminars. There are reports that several other companies are also resorting to the same practice, giving scant to regard to the MCI's notification that restraints doctors from accepting gifts.
Like accepting a gift, giving a gift is also equally wrong. At present, we cannot take any action against the pharma companies for giving gifts to the doctors. So, we sought an amendment in the Drugs and Cosmetics Act to bring the pharmaceutical companies under the ambit of the law in making them punishable for rolling out freebies to the doctors for promoting their medicines, Dr Desai said.
He said that the MCI has asked the Drug Controller General of India (DCGI) to ask the pharma companies to restrain from such unethical trade practices.
Dr Desai also said that even though the MCI had written letters to the doctors and the pharma companies involved in the recent controversy, they did not respond to the MCI so far.

So-- the folks who function for India as equivalent to state medical licensing boards in the US, if I get the picture, have already told docs they may lose their licenses if they take any stuff at all from drug companies--and now want the law to prohibit the companies from offering the stuff in the first place.

I have suggested in my initial comment that India is "ahead" of the US in this area, and I believe that to be so in recognizing the depth of the problem. But I did not mean that as to suggest that I personally favor a criminalizing solution to the problem. I have from the get-go tried to argue that this is a matter of medical profesisonalism, and the integrity of medical practitioners, rather than legal penalties, would ideally govern. That of course requires that we medical folk hurry up and develop some integrity!

NIMH Director on Industry Influence over Psychiatry

The current JAMA (subscription required) features a commentary by Dr. Thomas R. Insel, Director of the National Institutes of Mental Health, on the problem of Pharma influence over psychiatry. Our blogging friends have quite different takes on the matter.

To Barney Carroll--
http://hcrenewal.blogspot.com/2010/03/dr-pangloss-as-nih-institute-director.html
--Dr. Insel has participated in a whitewash, spending most of the commentary making excuses that psychiatrists are at the pharmaceutical industry trough about the same amount as the pigs from other medical specialties, so it is unfair to single them out. Dr. Carroll opines that this whitewash may be motivated by Dr. Insel's close ties with Dr. Charles Nemeroff, whose escapades we have detailed on numerous occasions and is basically the poster child for academic psychiatrists eagerly doing the bidding of industry. Dr. Insel alludes elliptically to "the resignation of a chair of a prestigious psychiatry department" as one of the "major effects" produced by heightened publicity around conflicts of interest in his field. (Nemeroff, as we have covered, resigned as chair at Emory but soon after was hired on as chair by Miami.)

To Danny Carlat--
http://carlatpsychiatry.blogspot.com/2010/03/dr-tom-insel-nimh-chief-scolds.html
--it is much more significant that Dr. Insel has severely scolded his fellow psychiatrists in a national medical forum. Just to add a bit of fuel to the debate, the first comment on Dr. Carlat's blog posting is from Dr. Insel himself, who disputes many of Dr. Carroll's facts regarding the close ties Insel allegedly had with Dr. Nemeroff.

So I read the Commentary in JAMA carefully to try to figure out whom I agreed with, and find myself in this instance backing Dr. Carlat's general take on the matter. I can see how Drs. Carroll and Carlat came to such different conclusions because the Commentary is strangely composed, and actually seems to be two commentaries published side by side. One, as Dr. Carroll states, is largely a defense of psychiatry against charges that its practitioners are of lower moral caliber than other specialists. The second, as Dr. Carlat correctly points out, is an attack on his specialty for allowing industry money to distract it from science and quality patient care. Dr. Insel focuses mostly on the many non-drug treatments for mental illness, which have been scientifically proven, and yet remain largely underused and in some cases unreimbursed due to psychiatry's love affair with medications.

Perhaps Dr. Insel made a calculation that he needed to include his first commentary, making excuses for psychiatrists, as a sort of sugar coating on the bitterer pill of his second commentary. If so, he may have miscalculated as mostly he just confuses the reader as to what his main point is. I'll hope that the "real" Dr. Insel is the guy who wrote: "[A]cademic leaders and their professional societies will need to transform what has become a culture of influence. The greatest threat to an era of improved public health stemming from the productive and ethically sound relationship among academia, industry, and practice is a defiant embrace of the status quo..."

Insel TR. Psychiatrists' relationships with pharmaceutical companies: part of the problem or part of the solution? [commentary] JAMA 303:1192-93, Mar. 24/31, 2010.

Now It's Time To Start Clearing the Land Mines..CER

As one who personally was very happy to see the health reform legislation signed today by President Obama, I wish I could take time out to celebrate this historic event; but my task here requires that I keep careful watch on who has made out like a bandit in this big sausage-making process. The press is starting to fill up with scorecards on winners and losers, and sadly, many of the special interests who are bringing you the mess that is U.S. health care today are big winners (one being the pharmaceutical industry).

This post follows up on previous posts such as:
http://brodyhooked.blogspot.com/2009/11/beware-cer-trojan-horse-in-senate.html

We noted there that the Senate bill had a much worse comparative effectiveness research (CER) provision compared to the House bill. Sadly the Senate version has now prevailed in the final bill. That prompted a cheery press release from PIPC (Partnership to Improve Patient Care):
http://www.improvepatientcare.org/news-media/pipc-applauds-new-health-care-bill%E2%80%99s-cer-language

PIPC is extremely pleased with the new comparative effectiveness research apparatus. That's because as we noted before:
http://brodyhooked.blogspot.com/2009/05/stealth-campaign-to-shanghai-ce.html
--PIPC is mainly funded by the drug industry and by some medical organizations like the American College of Cardiology (which should be ashamed) that want to be sure that CER never exposes their lucrative gravy trains and puts a stop to their profits by pointing out that the same medical benefits could be achieved at much lower cost. Therefore PIPC has been waging a stealth campaign, superficially applauding CER while trying hard behind the scenes to be sure that CER never gets to grow any teeth. So PIPC really likes the Senate version, that avoids giving control of CER to a group like the Agency for Healthcare Research and Quality, that actually could manage CER effectively and wisely, and creating a private body to oversee it--assuring that representatives of industry (who have no place on any such board that is serious about its business) are well represented. (All in the noble cause, of course, of keeping government out of your health care decisions.)

It will be essential for all who believe that we need genuine CER, that addresses cost issues alongside of benefit and safety issues, to move as quickly as possible to amend that section of the legislation. Put that near the top of your Post Reform To-Do List.

Along for the Reform Ride: Sunshine Legislation

We have focused much less lately on the Physician Payment Sunshine Act, in part because the legislation had become bundled into the larger Senate health reform bill and hence awaited the fate of that legislation. So it was easy to forget last night that Sunshine was along for the ride when the House passed the Senate version of health reform. Thanks to our friends at the Pew Prescription Project for this announcement:

PEW STATEMENT ON THE PHYSICIAN PAYMENTS SUNSHINE ACT

WASHINGTON – Allan Coukell, director of the Pew Prescription Project, issued the following statement today, commending Congress for including provisions from the Physician Payments Sunshine Act in health care reform legislation. The provisions would require drug and device companies to publicly report the gifts and payments they make to doctors.

“Patients deserve to know if their doctors are receiving money from drug companies. Congress has added much needed transparency to the financial relationships between the pharmaceutical industry and physicians. The reporting requirements in the health care legislation will better protect patients and will help restore trust in our health care system.

“A study in the New England Journal of Medicine reported that more than 90 percent of physicians have some financial relationship with the pharmaceutical industry. We also know that companies spend at least $25 billion each year marketing to doctors. While many relationships between academic medicine and industry are necessary and beneficial, they create potential conflicts of interest that can influence prescribing and drive up costs.

“This new legislation will enhance the safety of consumers by increasing transparency while in no way restricting business or limiting innovation.”

BMJ Study: COI Associated with Substantial Bias on Rosiglitazone Dangers

In HOOKED, I mentioned a classic study by Stelfox et al. (NEJM 338:101-6, 1998) showing that financial conflicts of interest were strongly associated with the position authors took on the potential risks of calcium channel blocking drugs. In those olden days, Stelfox et al. found that only 3% of the articles they surveyed explicitly disclosed authors' COI.

To see what progress we have made since then, Dr. Amy T. Wang and colleagues in internal medicine at the Mayo Clinic decided to do a review of comments made after the publication of two major studies on rosiglitazone, one claiming that there was increased risk of heart attack, the other minimizing such risk. Their results have been published on line in BMJ (subscription required). (Hat tip to Dr. Roy Poses and the Health Care Renewal blog for mentioning this paper.)

Using careful statistical methods the authors first retrieved a set of papers (including editorials and letters to the editor as well as research studies) that cited the two initial studies. They did extensive searches to identify whether the authors had any COI with the makers of rosiglitazone, the makers of its major competititor drug, pioglitazone, or of any other oral diabetes drug. They then blindly classified the contents of each paper as positive/negative as to the heart attack risks of rosiglitazone and/or as recommending/not recommending its continued use.

Bottom line: even in this supposedly more enlightened age they found explicit COI statements in only 53% of the 202 papers they surveyed. The found authors with COI more than 3 times as likely to be positive about rosiglitazone or to recommend its use.

The results also argue against a rationalization sometimes heard by defenders of taking industry largesse--that if you take bribes from enough different companies, they all cancel out in the end. COI was associated with a greater likelihood of minimizing heart risk and recommending rosiglitazone whether the company from which the author had received payment manufactured rosiglitazone, pioglitazone, or another diabetes drug. Wang et al. did note, however, that of the 29 articles that they found in which strongly recommended using pioglitazone rather than rosiglitazone, 25 were written by authors being paid by pioglitazone manufacturers.

In short, the evidence continues to mount that COI does bias physicians' judgment, even though an association cannot prove cause-and-effect. And it seems that once you start getting financial goodies from drug companies, it becomes less important exactly which companies paid you; you begin to see drugs generally in a favorable light and to minimize risks of adverse reactions.

Wang AT, McCoy CP, Murad MH, Montori VM. Association between industry affiliation and position on cardiovascular risk with rosiglitazone: cross sectional systematic review. BMJ 2010; 340:c1344, doi: 10.1136/bmj.c1344

Into the Slammer: Only Answer for Pharma Misdeeds?

Now that our friend, Dr. Roy Poses over at the Health Care Renewal blog, has returned from a trip, I can put my feet up and go back to letting him write this blog for me.

Latest over his way is a post about King Pharmaceuticals having to pay a $42M penalty for a kickback scheme involving the long-acting morphine drug, Kadian:
http://hcrenewal.blogspot.com/2010/03/king-pharmaceuticals-settle-and-one.html

It's been mentioned numerous times that such penalties, that seem so massive to pore ol' folks like us and really are so piddly compared to the profits made by the big drug companies, can be treated by those companies simply as the cost of doing business and form no deterrent whatsoever to future misdeeds of the same sort. As Ann Woolner writes in Business Week, in a column cited by Health Care Renewal:
http://www.businessweek.com/news/2010-03-16/jail-time-for-executives-might-stop-drug-crimes-ann-woolner.html--

The biggest fine ever imposed in U.S. history, $2.3 billion against recidivist Pfizer, represented a mere 14 percent of the revenue stream from selling the drugs at issue over seven years.
So immune to criminal sanctions was the New York-based company that it launched its off-label Bextra campaign at the same time the company was pleading guilty to doing precisely the same thing with other drugs. The anti-inflammatory medication was later yanked from the market because of increased risk of heart attacks and stroke.

This leads Woolner to wonder what would work, which is the main point of the HCR blog post. The FDA could effectively shut down the drug company, which would throw a lot of innnocent people out of work in the middle of the recession and deprive patients of the useful drugs that company makes. A much better alternative, she says, is to note that while felony convictions of individuals--such as responsible company executives--are very difficult because you have to prove intend to defraud, the FDA is empowered by current law to engage in misdemeanor prosecutions, which require a much lower burden of proof. By those means, Woolner says, you might actually get some of the responsible parties to do a little jail time. And maybe that would grab the industry's attention in a way we have so far failed to do.

It Matters What We Call It

The Hastings Center, a bioethics and policy think tank, put out a news release today on a research study conducted by some of its people on bipolar disorder in children:
http://www.thehastingscenter.org/News/Detail.aspx?id=4567

The study reported the findings of a series of interdisciplinary workshops, and took a dim view of the recent tendency to liberally diagnose chaildren with behavioral problems as having bipolar disorder and treating them with powerful medications frequently used for adults. The report urges use of two newer diagnostic labels, Severe Mood Dysregulation (SMD) or Temper Dysregulation Disorder with Dysphoria (TDD). These, the investigators, say, really amount to "we don't know what causes this" and therefore tend to avoid prompting the use of unproven and potentially dangerous medications and other interventions.

In past posts I've noted the unholy alliance between drug industry marketing and a handful of academic psychiatrists who have been zealots for bipolar disorder in kids--such as: http://brodyhooked.blogspot.com/2009/03/lets-cut-dr-biederman-some-slack-just.html

The present report, however, notes an additional wrinkle that deserves comment: the workshop group universally agreed that “children and families can suffer terribly as a result of serious disturbances in children’s moods and behaviors,” and that these troubled children desperately need help. They also write, “It is a deeply regrettable feature of our current mental health and educational systems that some DSM diagnoses are better than others at getting children and families access to [needed] care and services.”

This, I think, is an excellent and underappreciated point. We often imagine that making a medical diagnosis is an objective, scientific, and completely apolitical exercise. In actuality, saying that somebody has disease X is almost always another way of saying, "I recommend that you treat this person in such-and-such a way." Often that amounts to a highly political statement, and in some environments, a very charged statement. (Witness the long fight over whether a group of sick veterans get to apply the term "Gulf War Syndrome" to whatever they have. We ought all of us to be able to agree, first, that these people have various illnesses; and second, that they deserve help for their illnesses. So just why, one might ask, does it become so very important exactly what this set of illnesses gets called? It is hard to avoid the answer that the issue is more political than scientific.)

If the problem exists for bodily illnesses, it exists in spades for mental illnesses. (And we can easily see why a group of vets would fight tooth and nail to establish the "reality" of Gulf War Syndrome if they thought that the only alternative diagnosis was, "it's all in your head.") Ideally, we should be ready to help people with all different sorts of mental illness at roughly a state of parity with our response to "physical" illness. In reality, we play favorites; those with some mental illnesses are seriously stigmatized and effectively denied good care, while those with some other mental illnesses get a variety of gains from the label they end up with.

So--take an illogical use of mental health diagnoses to create a set of winners and losers among those who end up with various different labels for whatever ails them, and then add the craziness of drug companies that want to market expensive drugs, regardless of what the evidence shows--and you have an especially toxic cauldron for causing harm to kids.

The impressive thing about media coverage of the zealot psychiatrists who drug these kids sometimes to death with multiple antipsychotic medications, is that each has the backing of a dedicated and vocal group of parents of their patients, who think they walk alongside God. Why? Because the psychiatrists agreed with the parents that their kids are indeed deeply disturbed, in ways that the parents did not cause and cannot understand. They then proceeded to try to help the kids, in however wrongheaded a way, with these drug cocktails--but one wonders if what made them heroes was not the "heroic" drug therapy so much as the simple, compassionate act of taking the parents seriously.

Survey of Comparative Effectiveness Studies: Major Gaps

A paper and an editorial in the most recent JAMA (subscription required) depict the current status of comparative effectiveness research (CER). Drs. Conway and Clancy of DHHS/AHRQ summarize the findings in the paper by Drs. Hochman and McCormick of Harvard. The latter looked at the 6 highest-impact general and internal medicine journals between June 1, 2008 and September 30, 2009. They evaluated 328 studies that looked at medications, and found that 104 of them were CER. They noted at only 11% of these CER studies compared medications with nonpharmacologic interventions, while 31% compared different pharmacologic strategies. Another major gap was that only 19% of studies focused on safety of medications. Only 13% of the CER was commercially funded.

Conway and Clancy note that federal funding for CER has recently increased as a result of the economic stimulus package. They also suggest what steps must be taken in the future to get the most out of CER. I am certainly no expert in this field but to me, what their comments suggest is the need in CER for something like the international Cochrane Collaboration for systematic reviews of the medical literature. That is, a coordinating body or clearing house that can assure reasonably uniform and high-quality methods, and identify areas needing study and areas where overlapping studies may be underway, is highly desirable. They mention the Federal Coordinating Council for Comparative Effectiveness Research and the Institute of Medicine as possible locations for this activity.

One thing that Conway and Clancy did not mention perhaps deserves comment--they say nothing in their editorial about linking CER to issues of cost of care or cost-effectivess. This may reflect fears of the Obama Administration over stoking any talk of healthcare "rationing" as the fight over health reform legislation intensifies. For the record, Hochman and McCormick noted that only 2% of the studies they surveyed addressed cost-effectiveness.

Hochman M, McCormick D. Characteristics of published comparative effectiveness studies of medications. JAMA 303:951-958, 2010.

Conway PH, Clancy C. Charting a path from comparative effectiveness funding to improved patient-centered health care [editorial]. JAMA 303:985-986, 2010.

Do Bisphosphonates Increase Fracture Risk? Considerations to Keep in Mind

WARNING: This post contains relatively more speculation and less evidence. Toward the end I will make an evidence-based comment.

As I was driving to work this morning, the local radio news broadcast a spot about fears that long-term use of bisphosponates such as alendronate (Fosamax) might increase risks of fractures in certain locations, leading the FDA to consider new warnings. The natural reaction one might have to such news would be to pooh-pooh the idea that a drug that (supposedly) builds stronger bones could be a cause of bone weakness.

To see why this possibility might be more reasonable than would first appear, I'll refer you back to an excellent book that I have not mentiooned here in a while, John Abramson's Overdo$ed America, and its excellent chapter on osteoporosis. Dr. Abramson there reported data (which he admitted were preliminary and not conclusive) on the mechanisms by which bisphosponate drugs work.

He reminded us that there are basically two types of bone. If bones were PVC pipes, hollow, then the main type of bone would be cortical bone. The other type of bone, trabecular bone, is the internal part that provides the cross-bracing within the hollow tube. It does not take much engineering know-how to figure out that the real contributor to stronger, fracture-resistant bones is the trabecular component. It is therefore worrisome that studies suggest that bisphosphonates selectively increase cortical bone and in some circumstances might even disrupt growth of trabecular bone.

Now, if you are trying to make bones stronger, you'd want a drug that increases trabecular bone. But if your goal is to market drugs, you are very happy with a drug whose sole impact is on cortical bone. That's because bone-mineral-density (BMD) machines measure cortical bone more than they do trabecular bone. So if your marketing plan is to sell bisphosponate drugs by encouraging as many women as possible to go in for BMD testing-- see http://brodyhooked.blogspot.com/2009/12/npr-how-osteopenia-became-treatable.html-- then you want a drug that once women start taking it, makes their numbers look better soon.

As Dr. Abramson pointed out, this helps to explain why bisphosponates show very little if any effectiveness in preventing fractures in women with osteoporosis unless they have had a previous fracture, and why there is virtually no evidence that they help women with the less severe stage of bone density loss, osteopenia--and why there is even a chance that bisphosponates might increase fracture risk in some women with osteopenia.

So we don't know the final answer by any means, but as more news comes out about bisphosphonates and fracture risk, we should keep these possible underlying mechanisms in mind.

Evidence-based comment: This is yet another example of the flaws of using surrogate endpoints to determine whether or not to prescribe drugs. So long as we continue to believe that making BMD numbers look better is the same as preventing osteoporotic fractures, or that making blood sugar numbers look better in Type II diabetes is the same as preventing serious diabetic complications, then we are not practicing smart medicine; we're doing pharmaceutical industry marketing.

Getting a Pharm-Free Education: What Works?

A conversation has been going on recently on the Healthy Skepticism list-serv about how hard or how easy it is for physicians to stay up to date on new drugs and therapeutics without relying on sources that are controlled or heavily influenced by the pharmaceutical and device industries and their marketing juggernauts. Dr. Mark McConnell, who practices internal medicine in LaCrosse, WI, offered a set of highly practical tips that seemed too good not to share with all readers. He's given me permission to reproduce his how-to list, to which I have just a couple of additional suggestions.

Dr. McConnell states that by adhering to his program the necessary investment of time needed to stay reasonably informed and up to date is about 5-10 hours per month. (Like anything else, I'll add, when you just begin to start using any of these sources, it will take a bit longer; once you become used to how each works and where to locate the information you need, your time will shrink.) Dr. McConnell notes that he does not have a specific set-aside budget for CME and so he uses his own funds for these programs and sources.

His core resources:

Oakstone's Practical Reviews in internal medicine
$400/year
http://www.cmeonly.com/ME2/Audiences/dirmod.asp?sid=169BFEB1B46447C79F7F4D0B70D0253B&nm=Product+Catalog&type=Commerce&mod=GenComJournals&mid=63594F04C705480CA3E0A9BAAEE18D0E&AudId=920904C7329349CDA12AB2FB770606B1&tier=3&id=908141712AE34A799974F093EB52E0E6

InfoPOEMs from Essential Evidence Plus
$79/year
http://www.essentialevidenceplus.com/index.cfm

Therapeutic Initiatives Drug Therapy review course
$1000/year
http://www.ti.ubc.ca/node/14

Prescriber's Letter
$88/year
http://www.prescribersletter.com/(S(izxxzx45ukr2sobec3nt2sym))/home.aspx?cs=&s=PRL

I just have two additional resources to comment on. One is a service that provides a monthly CD with an audio presentation and evidence-based discussion of 40 recent articles pertinent to primary care, along with a database that allows you to store all 40 abstracts each month on your computer and later search them--Primary Care Medical Abstracts, http://www.ccme.org/PCMA/index-frame.html, $279/year. Rick Bukatra and Jerry Hoffman present, discuss, and argue about the abstracts in a manner somewhat reminiscent of "Car Talk" on NPR.

Second, I have been a long-time satisfied subscriber of The Medical Letter, http://www.medicalletter.org/, $98/year. This is supposed to be the Granddaddy of all U.S. non-commercially-sponsored publications on therapeutics, having been founded in 1959. The Medical Letter was being criticized on the HS list for not being truly independent and for allowing companies to review its assessments of their drugs. All I can say in defense of my longstanding use of this source (when I was in practice, which I am not currently) is that the publication hardly ever endorses a new drug, and most often says that a new drug is really no better than an older drug. The few times I have mentioned this publication to a drug rep, he has pooh-poohed it vigorously and given me numerous reasons why I should pay no attention. So if the drug companies are allowed to see the reviews, it does not appear that they have much influence over what is eventually published. I'd appreciate more discussion of this in the Comments.

None of the above sources accept ads from industry.