What We've Been Reading This Past Week

~ Stem-cell ‘tourists’ travel to where they have access to controversial stem-
cell therapies/ treatments.

~ Every baby born a decade from now will have its genetic code mapped at
birth predicts head of genomics company. Just because we can, does that
mean we should?

~ More docs tell pharma reps to keep out. Does this mean no more free post-
its?

~ Comprehensive reform bill that would have banned pharma gifts to docs voted
down in Colorado.

~ Experts say consumers should have more facts in drug ads so they can make informed decisions.

~ Glaxo to cut prices on drugs sold in poor countries. They will also invest
profits in building clinics in those countries.

~ The U.S. drug industry has shifted most of its clinical trials to overseas
sites raises serious ethical concerns.

~ U.S. court: No link between vaccines and autism.

~ Pfizer owes damages for bilking Wisconsin Medicaid.

~ EU governments have no right to conceal the location of field trials of genetically modified (GM) crops.

~ Men may be their own worst enemy when it comes to their health.

~ Women on the other hand …: Coffee drinking lowers women’s stroke risk. Ooooh, imagine a Starbucks ‘pharmacy’ on every corner …

~ BUT, too much soda can kill a girl’s kidneys.

~ Deadly bacteria defy drugs, alarming doctors. Is this an argument for or against anti-bacterial soap? You decide!

~ Llama’s have unique antibodies that one day might be used to treat immune system diseases in humans.

~ Scientists have unraveled the genetic code of the common cold. Spectacular!

~ Decoy molecules drive cancer cells to suicide.

~Altered virus effectively delivers new gene to replace faulty one that causes CF and completely rids the lung of disease. I wonder if these researchers have seen I Am Legend?

~ Researchers have discovered that the good bacteria found in dairy products might also be an effective vehicle for an oral vaccine that can provide immunity to anthrax exposure.

~ A new study indicates that a pneumonia vaccine can significantly cut the risk of heart disease.

~ Oh, Baby: A prenatal link to Alzheimer's?

~ Doctors have identified two genetic mutations that control the growth and
development of malignant gliomas; maybe good news for brain tumor patients.

~ Cotton candy as a substrate to re-grow vascular tissue.

~ Biotechnology's potential barely exploited.

~ Stimulus package includes funds for comparison of the effectiveness of
medical treatments.

~ President Obama to lift ban on embryonic stem cell research soon.

~ Scientists and doctors try to qualm public fears about vaccines and autism.

~ Scientists preparing to storm Capitol Hill on March 25 (a.k.a. the million
scientist march?). Registration ends Feb. 23.

~ No European stem cell patent for spinal cord repair.

~ Retired nurse invents cough, sneeze cover. Maybe she can convince the
airlines to make these standard issue …

~ FDA approves new and improved treatment for gout (the first in 40 ~years!).

~ But agency second guessing another …Savient gout drug faces approval delay.

~ FDA orders Bayer to correct earlier claims in Yaz birth control ad.

~ FDA deliberately backed off of "Good Laboratory Practice" requirements for
medical device makers.

~FDA wants one strain changed for next flu vaccine.

~ Orphaned baby chimpanzees cared for by humans in a loving, attentive manner have been found to be more cognitively advanced than some human infants. But, then, is this really that weird? They do share over 99% of our DNA.

~ Parody: FDA Approves Depressant Drug For The Annoyingly Cheerful.

[Thank you to Lisa von Biela, JD candidate, 2009, UMN, Editor of the BioBlurb, from which this content is partially taken and edited. BioBlurb is a weekly electronic publication of the American Bar Association's Committee on Biotechnology, Section of Science & Technology Law. Archived issues of the BioBlurb, as well as further information about the Committee on Biotechnology, are available here.]

FDA Approves Depressant Drug For The Annoyingly Cheerful

[Hat tip to Jay Vos at Blazing Indiscretions for bringing our attention to this parody] At last, Big Pharma has come out with a drug designed to treat the symptoms of excessive perkiness. For those with an annoyingly chipper attitude towards life:




Cool Beans!

From Across the Pond, along with Mary Poppins, Paracetamoxyfrusebendroneomycin!

[Hat tip to Dr. Joan Bushwell's Chimpanzee Refuge blog, for bringing this Amateur Transplants masterpiece to our attention and with all apologies to all those who know have the Mary Poppins tune stuck in their heads.]

And wishing you a very funny New Year!

Off Label meds are the REAL worry, not placebos

Art Caplan brings us all up to speed in his latest MSNBC column:

Last week, a newly released study showed that half of all American doctors who responded to a nationwide survey say they regularly prescribe placebos to patients. This news captured a lot of media attention and elicited a round of ethical hand-wringing with many experts wondering if systematically deceiving patients by giving them placebos without telling them was right. But ironically, there is a paper out this week in Public Library of Science Journal that is getting nowhere near the same attention as the placebo study, but raises a far more serious concern: Doctors prescribing off-label medicines that may not work.

In 2001, the last year for which data is available, American physicians wrote 150 million prescriptions off-label to treat conditions for reasons other than the ones for which the drugs were approved. This represents 21 percent of all prescriptions written for 160 of the most common medications used in the United States. About three-quarters of all off-label prescriptions were written for conditions for which there was little or no scientific support to show that they worked.

The manufacturers of these drugs apparently believe the practice is ethical. In the article, two physician researchers, Dr. Adriane Fugh-Berman and Dr. Douglas Melnick, say that despite the fact that it is illegal for pharmaceutical companies to promote drugs for off-label uses, drugmakers still find ways to do so — primarily because there is so much money to be made from the practice.

Drug companies sometimes seek approval from the U.S. Food and Drug Administration for an obscure use for a new drug knowing that it is likely it will be picked up for much wider use off-label. A “decoy” indication for a rare or unusual condition may get a drug approved quickly while the company gears up a subtle campaign to suggest off-label uses for which no data has been given to the FDA.

Doctors not bound by same rules
The key to encouraging off-label use is to make sure no one working for the company suggests any such thing. But if prominent, respected physicians can be recruited to give talks for the company concerning a drug, they are free to say what they want about possible off-label uses.

Flooding medical meetings with abstracts, posters and other additions to programs that are not obviously sponsored by industry creates more buzz for possible off-label uses. These practices are so lucrative that some drug companies pursue them even at the risk of huge fines. In the past few years, Schering Plough, Cell Therapeutics, Purdue-Pharma, Cephalon and many other companies have paid billions in fines even as the practice of surreptitiously promoting off-label uses flourishes.

What we now have is a huge amount of money being spent on what are often placebos. The system for regulating off-label use is not working and needs to be toughened. And it makes sense for the next presidential administration to consider creating an agency that can serve as an independent, publicly funded source of data on the safety and efficacy of off-label use of drugs.

Until changes are made, what you really need to know from your doctors is not whether they are using placebos but whether the drugs they prescribe for you are off-label and why.

Big Pharma gets caught ghostwriting

From the NYT comes the news that Merck flacks were the real authors of "dozens of research studies" on Vioxx that were then shopped around to name-brand physicians. (WaPo reports as well, here.) Presumably, docs who agreed received some kind of compensation--even if it was just another publication, which is the currency of academic science--for adding their names to the papers and submitting them to journals for peer review and publication. You can read the source article from the Journal of the American Medical Association here.

What's the big deal? Well, for starters, there's the potential for conflict of interest when a drug manufacturer (or anyone else) writes up positive research results about a product in which they have a financial interest. Disclosing such interests is the usual "solution." In this case, there wasn't just non-disclosure; rather, there seem to have been purposeful steps to make it appear as though Merck wasn't involved. Moreover, from the standpoint of research ethics, it's not kosher for people to attach their names to papers they had no role in writing, or research they weren't involved in.

The news also raises the question of whether the research results reported are, in fact, valid and trustworthy. Journal articles are the primary way the medical community learns about advances in clinical care. If people or corporations are willfully putting bad information into the system, patients could suffer or be harmed as a result. The sketchy track record of Vioxx, combined with the news that at least some of the studies that encouraged its adoption in clinical practice might have been written by its manufacturer .... well, it doesn't look good for Merck.

Tainted Drugs*

A state-owned Chinese pharmaceutical company is at the heart of an international drug scandal after it's been revealed that over 200 patients were paralyzed or otherwise hurt by tainted leukemia drugs last summer. But in what we sometimes cynical Westerner's might consider a surprise, given recent cover-up history (especially regarding lead in toys), China's Food and Drug Administration has been at the heart of chasing down the pharma company managers, and responsible for closing the plant when the tainted drugs were discovered.

This would be alarming news to receive about any major pharma company, regardless of their involvement in the import/export industry, but the fact that Shanghai Hualian is the sole supplier of mifepristone (RU-486) for the United States raises even bigger concerns.

So far, the contaminated medications have been isolated to a factory about an hour away from the one that makes RU-486, but obviously when a company has one manufactoring problem, concern spreads to the entire system.

The United States Food and Drug Administration declined to answer questions about Shanghai Hualian, because of security concerns stemming from the sometimes violent opposition to abortion. But in a statement, the agency said the RU-486 plant had passed an F.D.A. inspection in May. “F.D.A. is not aware of any evidence to suggest the issue that occurred at the leukemia drug facility is linked in any way with the facility that manufactures the mifepristone,” the statement said.

When told of Shanghai Hualian’s troubles, Dr. Sidney M. Wolfe, a leading consumer advocate and frequent F.D.A. critic, said American regulators ought to be concerned because of accusations that serious health risks had been covered up there. “Every one of these plants should be immediately inspected,” he said.

The director of the Chinese F.D.A.’s drug safety control unit in Shanghai, Zhou Qun, said her agency had inspected the factory that produced mifepristone three times in recent months and found it in compliance. “It is natural to worry,” Ms. Zhou said, “but these two plants are in two different places and have different quality-assurance people.”

And while I do see this point, and agree with it to a degree, but given recent concerns both about the FDA and it's process, as well as China covering up manufacturing and health issues... I would certainly feel a lot better if the FDA released something more concrete than a no comment. That the FDA won't reveal what other medications are made/imported by the company also is worrisome. Again, on the one hand, I can understand not wanting to run consumers off by fear - but on the other hand, a lot of pets died because of contaminated food. Do we want to see the same health risks in our medications?

-Kelly

(*And as an aside, apologies to anyone else who now has Soft Cell's Tainted Love spinning 'right round in their head.)
-Kelly

Closing the Loopholes for Big Pharma

Today's New York Times reports that about a third of the studies done on Paxil and Prozac went unpublished and (not surprisingly) if those studies were included these drugs were much less effective than when only the positive studies were published. http://www.nytimes.com/2008/01/17/health/17depress.html?
This is only the latest in a series of revelations about the way that pharmaceutical companies (“Big Pharma”) control the data about new drugs which they make available to the FDA in seeking approval and then to the public. No one disputes that these failures to disclose are harmful to the public’s health. Doctors prescribing drugs and using medical devices must have complete information in order to make the best treatment decisions. However, what is lost amidst the hand-wringing is that there is a very simple way to end this pattern and to make this information available to those who need it: require that all information, positive and negative, about drugs submitted for approval to the FDA be made available to a public data base. Current regulatory changes to require greater disclosure are inadequate because if there are any places left to hide negative data, Big Pharma will find a way to get there. Moreover, the arguments that it is somehow unfair to require companies to benefit from information about what doesn't work makes no sense because companies would only have to disclose AFTER they decide it is worth submitting the drug for approval.

Pharmaceutical companies are businesses like any other and are entitled to make a profit and to keep business information private—but only to the extent that it does not harm the public’s health. Having a drug approved for sale in the United States by the FDA is a privilege and it should come with the responsibility of making available all the available information—not just the information which the company chooses to disclose.

While it has always been the case that pharmaceutical companies were able to hide negative results in studies they conducted themselves, the need is much greater following a recent Supreme Court decision, Garcetti v. Cebalos, which held that government employees do not have First Amendment protection for divulging information—even information vital to the public’s safety-which they learn at work. Most people do not know that a growing number of research companies conducted by pharmaceutical companies are channeled through academic medical centers. While Garcetti v. Cebalos, did not involve research scientists it clearly suggests that a medical researcher at a state university which conducts drug trials for pharmaceutical companies could put his or her job at risk by divulging negative results. This silencing of whistleblowers means that without specific legislation that requires the disclosure of all data, wherever acquired, companies can continue to shield negative results from public view.

Of course is o.k. for pharmaceutical companies to make a profit, just as it is for auto companies, but when the product is one that can endanger the public’s health there must be a requirement of full disclosure.


Jennifer S. Bard, J.D., M.P.H.
Alvin R. Allison Professor of Law and Director, Health Law Program Texas Tech University School of Law Associate Professor (Adjunct) Texas Tech University School of Medicine
1802 Hartford Avenue
Lubbock, Texas 79409-0004
Jennifer.Bard@ttu.edu
806.742.3990, ext. 349


http://www.nytimes.com/2008/01/17/health/17depress.html?ex=1201237200&en=bff3cb16e49ff5f0&ei=5070&emc=eta1

Big Pharma and Informed Consent

A colleague asked me to post this entry under the nom de plume J. E. Cochran -- a thought provoking post, I thought:

Informed consent, in a clinical trial, requires that a clinical trial subject be fully informed of all the risks and the benefits of taking part in the trial before participation. The goal of informed consent is that the subjects should have all relevant information, and be able to make their own decisions as to whether they should participate in the clinical trial. This approach is complicated not only because of the complicated information that must be presented to the subject,
which can rarely be fully understood, but also the fact that the information must be kept a secret for business reasons.

The requirement of informed consent, was proposed by physicians, ethicists, and even the US Food and Drug Agency (FDA) and the International Committee on Harmonization (ICH). However, while informed consent does invoke a warm fuzzy feeling and is great PR for
the pharmaceutical industry, the practical procedures and implicationsare far from having been completely worked out.

Pharmaceutical companies spend hundreds of thousands of dollars a year protecting their intellectual property by using patents, trade secrets, copyrights, etc. Accordingly, the investigators, subjects, institutions and all other related personnel who would have access to
the drug or its data are subject to strict confidentiality provisions. Practically speaking, however, it is commonly known that researchers talk amongst themselves and patients routinely discuss their treatment protocols with each other. Drug companies hope to curtails this
practice but realize that they have little choice but to "play along." The research industry chooses from only 3-5% of the entire practicing physician population. This population not only does the required research to approve a drug, but consists of key opinion leaders and a
significant portion of the initial prescribing population. In light of the clout of this researcher population, the industry prefers not to antagonize this population by the stringent enforcement of the confidentiality provisions. The practice of stringent enforcement of confidentiality provisions becomes even murkier when we talk about allowing patients to see the Investigator's Brochure (IB).

The IB is a grouping of the significant scientific data, in the original scientific language, which is made available to the investigator so that the investigator knows all the relevant risks
and benefits when enrolling patients. Conversely, the informed consent form is a significantly simplified document that hopes to inform patients, in a language that they can understand, of only the most important risks and benefits. The trade-off, caused by the use of this simplified language, is that a lot of the risks are not completely addressed in the standard informed consent form.

The question therefore arises: Considering the private and proprietary nature of new chemicals entities (NCEs), and the possible lack of complete information in the typical informed consent form, can a potential subject, request to have access to not only the informed consent form (which the subject is usually required to sign or acknowledge), but also the investigator's brochure?

Pro Business and intellectual property (IP) advocates, as advised by their lawyers, err on the side of protection of the data. They believe that the data generated from the drug can save lives, if only given a chance, and provided a profit can be made on the drug. They believe that this profit can only be made if their drug remains unique and the data generated from their studies is not mis characterized. They hence assert that the patient should only have access to the data that is meant for them and provided since that information has been customized for them such that it is easy for them to understand and difficult to mis-characterize. On the other hand, the drug companies believe that the data provided in an IB is difficult for the lay person to understand, and easy to mis characterize. Furthermore, if that data is provided to competitors, it can serve as a source of erosion of profits since the competitors will either mis-characterize
the data or develop me-too products. To avoid all these complications, pro business and intellectual property advocates err on the side of protection of the data.

On the other hand, patient rights advocates believe that despite the confidentiality provisions, the subject must have access to all data. These advocates believe that the understandability of the data is a significant goal, but should not be a barrier to access to this data. They point out that informed consent cannot occur in the absence of complete information. They also assert that the fact that subjects may not understand the data is an inadequate explanation since the
information should be phrased such that it can be easily understood. (IP advocates point to the inherent risks in over warning and the lack of focus present in 40 page informed consent forms.)

Both sides have valid concerns, each of which must be addressed. However, these concerns must not only be addressed in the vacuum of academia but in the bustling streets of commerce with true capitalism testing what the market supports.

For more info on this subject, click here.

Jumping Rope with Abe Lincoln and a Groundhog

We've all seen the commercials and print ads for Rozerem, and you must admit how clever you think they are. Also, we've probably all encountered difficulty with sleeping, sometimes days-sometimes a few weeks at a time. I would be hard pressed to ever consider taking any sort of sleeping aid, prescription or OTC (with the exception of an occasional dose of Nyquil), but I have definetely experienced those bouts of poor sleeping. As our lives become increasingly busy and hectic, I think perhaps cutting back on caffeine and engaging in more physical activity (two things which are beneficial in more ways than just as sleep aids) are more healthy and desirable alternatives to help get to sleep at night.

But I did appreciate how some may feel inclined to take a sleep aid. Until now. The New Times published an article this week reporting that sleeping pills are really just mildly effective, that the newer drugs tested cut the time it took to fall asleep by only 12.8 minutes, and increased total sleep time by only 11.4 minutes. Is taking a prescription and ingesting more chemicals worth that? I don't think so.

And that is not all. The same article also reports that older prescription sleep aids such as Halcion and Restoril accounted for signicantly better results than the newer drugs. Yet another case of unneccessary "Me-too" drugs being overly marketed and preying on people who may be in a vulnerable state, in this case, sleep-deprived. As I mentioned above, most people find the Rozerem ads charming; they may march into the doctor's office and specifically request Rozerem. Note the Times article reports Americans spent $4.5 billion dollars on sleep aids last year.

Basically, sleeping pills don't really work, or rather, just aren't as effective as the American consumer is led to believe, according to the analysis. Pharmaceutical companies are latching onto our weaknesses and trying to tell us once again that it can all be solved in a little pill. And if Americans are spending that much money every year on sleeping pills, then it appears physicians are also throwing in the proverbial tower by prescribing these pills. Too bad these physicians can't be like the doctor in Fight Club who tells Tyler Durdan to "get more exercise and chew some valerium root, " instead of prescribing sleeping pills.