Drug Injury Watch

The Tale Of Merck's Fake Medical Journal As Told At A Vioxx Trial In Australia

Drug Company Paid Scientific Publisher Elsevier To Produce What Was Essentially A Marketing Publication For Vioxx And Fosamax

(Posted by Tom Lamb at DrugInjuryWatch.com)

In early April 2009 we heard that there had been some testimony at an Australian Vioxx personal injury trial about a "medical journal" which Merck had created and distributed to doctors in Australia apparently to tout the benefits of its (now recalled) blockbuster drug Vioxx.

Now an April 30, 2009 article, "Merck publishes fake journal", published online by The Scientist (free site registration required), gives us some additional information about what Merck was doing in Australia back in 2003:

Merck paid an undisclosed sum to Elsevier to produce several volumes of [Australasian Journal of Bone and Joint Medicine,] a publication that had the look of a peer-reviewed medical journal, but contained only reprinted or summarized articles--most of which presented data favorable to Merck products--that appeared to act solely as marketing tools with no disclosure of company sponsorship.

"I've seen no shortage of creativity emanating from the marketing departments of drug companies," Peter Lurie, deputy director of the public health research group at the consumer advocacy nonprofit Public Citizen, said, after reviewing two issues of the publication obtained by The Scientist. "But even for someone as jaded as me, this is a new wrinkle."

According to this article by Bob Grant, The Scientist obtained two issues of the Australasian Journal of Bone and Joint Medicine, Volume 2, Issues 1 and 2, both dated 2003.  Those issues were reviewed by Public Citizen's Peter Lurie, and the article some comments by Mr. Lurie about his review:

"I've never seen anything quite like this," he said. "Reviews are usually swimming in references." For example, one article on osteoporosis labeled above the title as a "meta-analysis" cites two references -- one itself a meta-analysis. "To the jaundiced eye, [the journal] might be detected for what it is: marketing," he said. "Many doctors would fail to identify that and might be influenced by what they read."

This April 30 article also draws upon testimony given at the trial of the civil suit filed by Graeme Peterson -- who suffered a heart attack in 2003 while on Vioxx -- against Merck and its Australian subsidiary, Merck, Sharp & Dohme Australia (MSDA):

In testimony provided at the trial last week, which was obtained by The Scientist, George Jelinek, an Australian physician and long-time member of the World Association of Medical Editors, reviewed four issues of the journal that were published from 2003-2004. An "average reader" (presumably a doctor) could easily mistake the publication for a "genuine" peer reviewed medical journal, he said in his testimony. "Only close inspection of the journals, along with knowledge of medical journals and publishing conventions, enabled me to determine that the Journal was not, in fact, a peer reviewed medical journal, but instead a marketing publication for MSD[A]."

He also stated that four of the 21 articles featured in the first issue he reviewed referred to Fosamax. In the second issue, nine of the 29 articles related to Vioxx, and another 12 to Fosamax. All of these articles presented positive conclusions regarding the MSDA drugs. "I can understand why a pharmaceutical company would collect a number of research papers with results favourable to their products and make these available to doctors," Jelinek said at the trial. "This is straightforward marketing."

As mentioned above, there was no disclosure of Merck's funding found anywhere in the two issues of the Australasian Journal of Bone and Joint Medicine obtained by The Scientist.  But reporter Bob Grant established that this "journal" was, in fact, paid for by Merck:

Elsevier acknowledged that Merck had sponsored the publication, but did not disclose the amount the drug company paid. In a statement emailed to The Scientist, Elsevier said that the company "does not today consider a compilation of reprinted articles a 'Journal'."

"Elsevier acknowledges the concern that the journals in question didn't have the appropriate disclosures," the statement continued. "It is worth noting that project in question was produced 6 years ago and disclosure protocols have evolved since 2003. Elsevier's current disclosure policies meet the rigor and requirements of the current publishing environment."

Mr. Grant's article also includes statements by a spokesman for Merck's Australian subsidiary, MSDA, as well as a rheumatologist in Australia who was one of the members of a "Honorary Editorial Board" for this Australasian Journal of Bone and Joint Medicine journal.

Last but not least:  Mr. Grant's article -- "Merck publishes fake journal" (free site registration required) -- provides links for you to view PDFs of the two issues of Australasian Journal of Bone and Joint Medicine from 2003 which were obtained by The Scientist.

P.S.  A new article, "Fresh questions raised about prominent cardiologist's role in "ghostwritten" 2001 meta-analysis of Vioxx trial", published April 30, 2009 by heartwire, is worth a look if this matter intrigues you.  (5/1/09)

Off-Label Prescribing Of Drugs: An Explanation And Some Practical Guidance For Patients

Don't Be Afraid To Talk With Your Doctor About Any Medication You Are Prescribed -- Especially If The Drug Is Being Used As A Treatment NOT Approved By FDA

(Posted by Tom Lamb at DrugInjuryWatch.com)

Let's start with an informal and short definition of so-called "off-label" prescribing: A drug is being prescribed "off-label" when it has not been approved for treatment of the patient's medical condition and, instead, is being used experimentally.

To put this practice into context, we draw from a provocative article, "Informed Consent and Shared Decision-Making: A Requirement to Disclose to Patients Off-Label Prescriptions", written by Michael Wilkes and Margaret Johns, which was published November 11, 2008 by the Public Library of Science (PLoS):

Because a basic premise of the US Federal Food, Drug, and Cosmetic Act is that manufacturers are prohibited from marketing drugs or devices without FDA approval, the public commonly assumes that all uses of prescription drugs have been approved by the FDA. However, after a drug is approved for one set of indications, researchers and doctors often discover new applications for it. Even when the FDA approves a drug for a single, specific use, doctors may legally prescribe the drug to any patient for any use. Physicians are not restricted to prescriptions that comply with the FDA approval. The FDA considers such treatments “off-label” because substantial evidence regarding their safety and efficacy has not been presented or evaluated. But such uses are perfectly legal. In fact, FDA policy explicitly states that “once a [pharmaceutical] product has been approved for marketing, a physician may prescribe it for uses in treatment regimes of patient populations that are not included in the approved labeling”. Indeed, as the Supreme Court has recognized, off-label prescribing “is an accepted and necessary corollary of the FDA's mission to regulate in this area without directly interfering with the practice of medicine”.  [footnotes omitted]

This PLoS article by Wilkes and Johns points out that, in fact, there are many examples of responsible off-label prescribing -- one is aspirin being prescribed to reduce the risk of heart attack long before it was FDA-approved for this purpose -- but cautions that other off-label uses can be dangerous -- a prime example is fenfluramine for weight loss, which caused heart valve damage to thousands of people (it was onepart of the notorious "fen-phen" combination).

So what should a patient do when it seems that their doctor is suggesting, or prescribing, a drug for an "indication", or treatment use, other than what that drug was approved for by the FDA?

The Agency for Healthcare Research and Quality (AHRQ) publishes online an advice column from Carolyn M. Clancy, M.D., who wrote "Off-Label Drugs: What You Need to Know".  Here is some guidance for patients offered by Dr. Clancy in that April 21, 2009 article:

Talk with your doctor if you have concerns about any medicine or treatment, particularly if it may be off label. Here are several questions to ask:

• Is this the approved use of the medicine? You may not know if the use is off label. This question can help you start the conversation with your doctor about your medicines. 
• Is the off-label use of this drug likely to be more effective than one approved to treat my illness? This is important because the off-label drug may not be as well tested for your condition.
• What evidence shows that this off-label drug can treat my condition?
• What are the risks and benefits of off-label treatment with this drug? Will my health insurance cover off-label treatment with this drug?

As we like to say at AHRQ, "Questions are the answer," meaning that it's important to ask your doctor plenty of questions about any medicines he or she prescribes. When you understand why you are taking certain medicines—including off-label drugs—you are more likely to take them correctly.

The bottom line is that you should not be afraid to talk with your doctor if you know or suspect that a drug is being prescribed off-label, i.e., as a treatment which has not been approved by the FDA.

April 2009 Update: Another Tysabri Patient Develops Serious Brain Infection PML

What Is Progressive Multifocal Leukoencephalopathy (PML), What Causes It, Why Is Tysabri Still On The Market?

(Posted by Tom Lamb at DrugInjuryWatch.com)

On April 17, 2009 we learned that another multiple-sclerosis patient using the multiple-sclerosis (MS) drug Tysabri developed progressive multifocal leukoencephalopathy, or PML, a rare brain infection.  This is the sixth MS patient who has been diagnosed with PML since Tysabri was reintroduced on the market in July 2006.

We get some insightful additional information from a Dow Jones article, "Biogen Says Sixth MS Patient On Tysabri Gets Brain Infection":

Tysabri - sold by the Cambridge, Mass., biotech [Biogen Idec Inc. (BIIB)] with Ireland-based partner Elan Corp. PLC (ELN) - was pulled from the market for 18 months beginning in 2005 because of a suspected link to the rare brain infection. Before Friday, the company had reported five confirmed cases, with one death, since the relaunch.

The latest case was outside the U.S., as were four of the previous five. Biogen didn't disclose additional details on the patient's condition.

Biogen plans to post a case update every Friday until July 24, the third anniversary of relaunch, by which time it expects the risk/benefit profile to be clearer.

The PML rate implied on Tysabri's label is one-per-1,000 patients. As of the end of March, about 40,000 patients were using Tysabri and about 24,900 patients have received at least one year of therapy. Chief Executive Jim Mullen, before Friday, had stressed the current rate for patients taking the drug more than 12 months is about one-per-4,000.

Some believe that duration of therapy plays a role in Tysabri's PML risk. The company said Thursday that about 6,800 patients have used the drug for more than two years, which is a rise of 2,500 from three months ago.

Earlier this month, on April 9, the biotech company Genentech announced that it was withdrawing its psoriasis medicine Raptiva from the market because it can cause PML. This Raptiva recall came after just four cases of PML had been reported in patients taking Raptiva, all of whom had reportedly been on Raptiva for at least three years.

The recent recall of Raptiva has some people asking this question: Why is Tysabri still on the market?

A good discussion of that question -- as well as an explanation of the PML disease process -- can be found in an April 20, 2009 Los Angeles Times article, "Psoriasis, Raptiva and PML: Why Genentech pulled the drug".  In relevant part:

Tysabri was pulled from the market in 2005 after three patients taking it for their multiple sclerosis developed PML. This was a big blow, because clinical trials had demonstrated the drug cut MS relapse rates -- bouts of worsening neurologic function -- by more than half. In June 2006, the Food and Drug Administration approved Tysabri's return to the market with a carefully crafted set of safety checks. Patients see their physicians monthly to be checked for features suggestive of PML -- basically, "anything new that can't be explained by the multiple sclerosis," Berger says. These include neurological symptoms, loss of white matter (which can be detected with MRI) and the presence of JC virus in spinal fluid.

Dr. Melvin Chiu, a dermatologist at the UCLA David Geffen School of Medicine who directs UCLA's Psoriasis and Phototherapy Center, says the situation with Tysabri differs from Raptiva when you consider the severity of the disease each drug is meant to treat. "That's not to say psoriasis is not disabling, but it doesn't have the life-threatening connotations that multiple sclerosis has," he says. "So from a risk-benefit analysis, it might not be worth the risk to be on Raptiva, especially given that there are several other therapies available for psoriasis patients that don't carry that risk."

We will watch for any additional reports of the brain infection PML in patients using Tysabri from Biogen -- which, as stated above, will be providing weekly reports at least  until July 24, 2009 -- or from other sources.

Drug Interaction Prevention Is An Ongoing Process For Doctors And Patients

An Introduction Using Examples And Facts Relevant To Avoiding Drug-Drug Interaction Risks

(Posted by Tom Lamb at DrugInjuryWatch.com)

Patients who require multiple prescription drugs at one time, i.e., concomitant use, are sometimes placed at risk for developing drug-drug interactions (DDIs), where one drug alters the effect of another drug. In turn, drug-drug interactions can lead to decreased therapeutic benefit or efficacy, adverse effects of varying degrees, or even patient death.

To further complicate this type of situation, non-prescription medications and herbal preparations or supplements can contribute to the potential for developing DDIs.

The following examples and facts are intended to help doctors and patients avoid drug interactions and their potentially serious, even fatal, consequences.  They are taken from an educational article, "Managing Drug-Drug Interaction Risks" (free site registration required), which is intended for physicians, pharmacists, nurse practitioners, physician assistants, nurses, and other healthcare workers -- but the information therein could be helpful to patients and their families.

• DDIs contribute to patient morbidity and may cause emergency department visits, hospitalizations, and re-admissions.Examples of patient morbidity caused by DDIs include gastrointestinal (GI) bleeding, renal dysfunction, electrolyte imbalance, hypertension, hypotension, bradycardia, arrhythmia, drug toxicity, and decreased drug effect.
• Examples from the literature of mortality associated with DDIs include ciprofloxacin in fatal seizures, moclobemide-clomipramine overdose in fatal serotonin syndrome,and fatal outcome from a warfarin and nonsteroidal anti-inflammatory drug (NSAID) interaction.
• [T]he risk for DDIs increases significantly after 44 years of age and is greatest for patients over 74 years of age. The need for multiple medications often arises with advancing age that may further the risk for DDIs.
• Patients taking 2 medications had a 13% risk while patients taking 5 medications had a 38% risk for DDIs. Patients taking 7 or more medications had an 82% risk of developing adverse drug interactions.
• Other patient-related risks for DDIs... include very young age, female sex, genetics, decreased organ function, use of a medication having a narrow therapeutic range (eg, warfarin, digoxin, and cyclosporine), major organ impairment, metabolic or endocrine risk conditions (eg, hypothyroidism, hypoproteinemia), and acute medical issues (eg, dehydration).

In the U.S., with our aging population and an ever-increasing use of prescription medications, it seems safe to say that the more one knows about the how to avoid possible drug-drug interactions, the better.

If you are aware of any additional guidance or resources regarding how to avoid drug interactions, please let us know by submitting a Comment, below.

April 2009 FDA "Patient Safety News" Videos For Doctors Online

Covers Bowel Cleansing Agents Visicol and OsmoPrep, As Well As Methadone Overdoses, Ethex Generic Drug Recall, And Medication Errors

(Posted by Tom Lamb at DrugInjuryWatch.com)

The FDA's Patient Safety News (PSN) is a series of monthly video news shows intended primarily for doctors and other health care professionals.  Generally, this series covers significant approvals, recalls, and safety alerts for prescription drugs and medical devices.  Some of the FDA PSN videos contain footage and demonstrations relevant to protecting patients from serious side effects and other unwanted consequences.

Subjects covered in the April 2009 edition of the FDA Patient Safety News include the following:

Stronger Warnings for Bowel Cleansing Agents

FDA is announcing new safety measures for oral sodium phosphate (OSP) products used for bowel cleansing before colonoscopies and other procedures. These products are associated with acute phosphate nephropathy, a rare but serious type of kidney injury. The events have been reported with the prescription products Visicol and OsmoPrep, and also over-the-counter sodium phosphate products when they are used as bowel cleansers.

Preventing Overdoses when Using Methadone to Treat Chronic Pain

A report from the Institute for Safe Medication Practices (ISMP) lists several reasons for the serious and sometime fatal overdoses that have occurred when methadone is used to treat moderate to severe chronic pain.

ISMP points out that methadone differs from other opioids in a number of ways. For example, methadone remains in the body long after its analgesic effect has worn off. Also, a patient may not experience the full analgesic effect of methadone until 3-5 days of use, so it must be titrated more slowly than other opioids.

Ethex Corp. Expands Recall of Generic Drugs and Supplements

The generic drug company Ethex Corporation is expanding earlier recalls to now include over 60 generic drug products, including narcotics and cardiac medications, as well as several dozen prescription prenatal vitamins and iron supplements. The company is taking this action as a precautionary measure because these products may have been manufactured under conditions that didn't comply with current Good Manufacturing Practices. Certain lots of some of these products were recalled earlier because of defects such as oversized tablets.                                                   

Avoiding Medication Errors with Multiple Brand Names

The Institute for Safe Medication Practices (ISMP) recently highlighted medication errors that can occur when a drug is marketed under more than one brand name, especially when one of those names is well established.

ISMP says that health professionals can reduce the risk of errors by conducting a thorough drug history and reviewing drug information if they encounter unfamiliar product names. ISMP also suggests that health professionals encourage patients to fill their prescriptions at the same pharmacy where possible, to help avoid taking the same product under different names.

One can find more information about this April 2009 PSN edition and the series in general on the Patient Safety News section of the FDA's web site.

A Timeline For The Psoriasis Drug Raptiva, From Product Launch In U.S. To Market Withdrawal

Raptiva Recalled in U.S. Due To Link With Fatal Brain Infection, Progressive Multifocal Leukoencephalopathy (PML)

(Posted by Tom Lamb at DrugInjuryWatch.com)

On April 8, 2009 Genentech Inc. -- which was just acquired by Roche Holding AG in March 2009 -- issued a press release announcing "a phased voluntary withdrawal of psoriasis drug Raptiva® (efalizumab) from the U.S. market" due to its link to a brain infection, progressive multifocal leukoencephalopathy (PML).

Here is a basic timeline for Raptiva, from product launch to drug recall.

2003:  Raptiva was approved by the FDA as a once-weekly injection for adults with moderate to severe plaque psoriasis.

October 2008:  FDA announced updated labeling for Raptiva to warn of the risk of life-threatening infections, including progressive multifocal leukoencephalopathy (PML).

December 2008:  U.S. sales of Raptiva were approximately $108 million in its last full year on market.

February 2009:  FDA issued a Public Health Advisory for Raptiva informing patients and doctors about the risk of PML in patients taking Raptiva, after receiving reports of four patients with PML, three of whom died.

February 2009:  The same day (February 19) that the FDA issued its Public Health Advisory, the European Medicines Agency announced the benefits of Raptiva do not outweigh its risks.  Accordingly, this regulatory body recommended that the use of Raptiva should be suspended in the European Union.

February 2009:  Two days later (February 21), at the recommendation of Health Canada, the marketing of Raptiva in Canada was suspended due to safety concerns, including the increased risk of developing PML.

March 2009:  FDA approved a Medication Guide for Raptiva and included additional information in Raptiva's labeling regarding PML.

April 2009:  Genentech announces "phased voluntary withdrawal" of Raptiva and sends out a Dear Healthcare Professional Letter, or "Dear Doctor" letter, about Raptiva as well as a Dear Patient Letter about Raptiva.

June 2009:  Raptiva will no longer be available to patients in the U.S.

To put this Raptiva recall into context, here is some information about progressive multifocal leukoencephalopathy (PML) from the April 8, 2009 Genentech press release about Raptiva:

PML is a rare, progressive, demyelinating disease of the central nervous system that leads to death or severe disability. PML is caused by activation of the John Cunningham, (JC) virus. The JC virus resides in latent form in up to 80 percent of healthy adults, typically only causing PML in immunocompromised patients. The factors leading to activation of the latent infection are not fully understood, though abnormalities in T-cells may be important for reactivation and PML. PML has been reported in the published literature in HIV-positive patients, as well as immunosuppressed cancer patients (including patients with hematologic malignancies), organ transplant recipients, and patients with autoimmune diseases. There are no known interventions that can reliably prevent or adequately treat PML.

Since FDA approval in 2003, approximately 46,000 patients worldwide have been treated with Raptiva, with approximately 2,000 patients in the U.S. currently receiving Raptiva at time this drug recall was announced in early April 2009 by Genentech.

FDA Presents Ten Years Of Summary Statistics For Its Adverse Event Reporting System (AERS)

Information Current As Of December 31, 2008; FDA Says It Will Provide Quarterly Updates For This AERS Data

(Posted by Tom Lamb at DrugInjuryWatch.com)

In early April 2009 the FDA released its Adverse Event Reporting System (AERS) Statistics as of December 31, 2008.

From that document, found on the FDA's web site, we get this contextual information:

The Adverse Event Reporting System (AERS) contains over four million reports of adverse events and reflects data from 1969 to the present. Data from AERS are presented here as summary statistics. These summary statistics cover data received over the last ten years. These data are presented at the individual report level; some of the numbers may reflect duplicate reporting due to factors such as follow-up reports received on a case or different persons reporting on the same patient case.

This summary of AERS statistics from the FDA is presents four different ways:

Reports Received and Reports Entered into AERS by Year (1999 - 2008)

Number of Domestic (U.S.) and Foreign Reports in AERS (1999 - 2008)

Reporting by Healthcare Providers and Consumers by Year (1999 - 2008)

Patient Outcomes by Year (1999 - 2008)

The third statistical analysis, which provides some breakdown on the type of person who submitted the adverse event (AE) report to FDA -- or submitted the AE report to the manufacturer which, in turn, sent the report to FDA -- was the one that I found most interesting. 

From this third analysis, Reporting by Healthcare Providers and Consumers by Year, we learn that in 2008 about 54% of the almost 500,000 AE reports were submitted by healthcare providers.  And for the 269,765 AE reports that were made in 2008 by healthcare providers, we get this further breakdown:

• Physicians: 154,044 AE reports in 2008
• Pharmacist: 27,070 AE reports in 2008
• Other types of providers (includes nurses, dentists, etc.): 88,651 AE reports in 2008

Any person who made an AE report to the FDA and who is not documented in the report as a healthcare provider was categorized as a "consumer".  About 46% of the 2008 AE reports were made by this group of reporters.

One might also look at the first analysis, Reports Received and Reports Entered into AERS by Year, to see the general trend upward for AE reports in the the past six years.

We look forward to receiving the quarterly updates to this summary of AERS statistics from the FDA in the future.

Marcia Angell's List Of Seven Things That Should Be Done By The New FDA Leadership

Dr. Angell, Former NEJM Editor-In-Chief And Current Harvard Medical School Professor, Writes An April 2009 Editorial For The Boston Globe

(Posted by Tom Lamb at DrugInjuryWatch.com)

Marcia Angell was the first woman to serve as editor-in-chief of The New England Journal of Medicine (NEJM).  Dr. Angell currently is a senior lecturer in the Department of Social Medicine at Harvard Medical School, in Boston, Massachusetts.

In the April 6, 2009 edition of The Boston Globe there is an editorial by Dr. Angell titled, "Charting a new course at the FDA", wherein she offers a list of seven thing that she thinks would return the FDA to its rightful purpose, "to ensure that [drugs] are safe and effective."

Dr. Angell's Boston Globe editorial should be read in full by anyone with an interest in the drug oversight aspect of the FDA's work.  As a preview, I have listed below the seven things that she would like to see Margaret Hamburg -- the nominated commissioner of the FDA -- and Joshua Sharfstein -- Hamburg's principal deputy -- do at the FDA in addition to (just) being the "new leadership".

• First, Congress should repeal the Prescription Drug User Fee Act.

• Second, consultants for drug companies should no longer be permitted to serve on FDA advisory panels.

• Third, the agency should see that the post-marketing studies it mandates are actually carried out.

• Fourth, the FDA should review generic drugs as fast as brand-name drugs.

• Fifth, Congress should give the FDA the authority to require drug companies to compare new drugs with existing drugs of the same type.

• Sixth, the FDA should stop approving me-too drugs on the basis of surrogate endpoints.

• Finally, the FDA should prohibit direct-to-consumer advertising for three years after drugs are approved.

After Dr. Hamburg has been confirmed by the Senate, I hope that she and Dr. Sharfstein will heed the guidance offered in Dr. Angell's April 6, 2009 editorial. 

FDA Staffers Tell Obama There Is Frustration And Outrage Over Misdeeds Of Former Agency Officials

In April 2, 2009 Letter They State There Is "systemic corruption and wrongdoing that permeates all levels of FDA" Which Needs To End

(Posted by Tom Lamb at DrugInjuryWatch.com)

ABC News has posted on their website a slightly redacted copy of an April 2, 2009 letter by nine FDA staffers -- apparently in the FDA's Office of Device Evaluation -- to President Barack Obama. 

This scathing (and seemingly unprecedented) letter was sent just days after President Obama appointed Dr. Joshua Sharfstein to be Acting Commissioner until Dr. Margaret Hamburg is confirmed as the new FDA Commissioner, hopefully, in the near future.

Here are the first and last paragraphs of this April 2009 six-page FDA staff letter to President Obama.

Dear Mr. President:

The purpose of this letter is to draw your attention to the frustration and outrage that FDA physicians and scientists, public advocacy groups, the press, and the American people, have repeatedly expressed over the misdeeds of FDA officials. Recent press reports revealed extensive evidence of serious wrongdoing by Dr. Andrew von Eschenbach, Dr. Frank M. Torti, top FDA attorneys, Center and Office Directors, and many others in prominent positions of authority at FDA. As a result, Dr. Frank M. Torti, Acting Commissioner and the FDA’s first Chief Scientist, abruptly left the Agency. But, the many other FDA managers who have failed to protect the American public, who have violated laws, rules, and regulations, who have suppressed or altered scientific or technological findings and conclusions, who have abused their power and authority, and who have engaged in illegal retaliation against those who speak out, have not been held accountable and remain in place....

All FDA employees who are committed to public integrity, who follow the laws, rules and regulations, who use science to promote public safety and health, and who have the courage and patriotism to speak out, must be protected and must have their professional lives restored.  We ask that you accept nothing less.

The names of the nine FDA staff members who signed this letter to President Obama were redacted, i.e., blacked-out, on the version that was posted on the ABC News web site.

Consistent with the authors of this letter, I hope President Obama ensures that the new leadership of our FDA restores the agency to its rightful purpose.

New Studies About Avandia And Actos Side Effects Other Than Cardiovascular Conditions

Glitazone Class Of Diabetes Drugs Can Increase The Risk Of Bone Fractures And Diabetic Macular Edema

(Posted by Tom Lamb at DrugInjuryWatch.com)

______________________________________________________________________________

UPDATE:  Avandia, Actos May Raise Risk of Macular Edema (MedPage Today, June 11, 2012)

The diabetes drugs pioglitazone (Actos) and rosiglitazone (Avandia) appear to substantially boost risk of macular edema in type 2 disease, an observational study found.

(6/13/12)

______________________________________________________________________________

In 2007 the FDA required a black-box warnings on the package insert, or label, of Avandia and Actos labels which states that these diabetes drugs should not be used in patients with advanced congestive heart failure (CHF). In addition, there have been several studies which show that Avandia may significantly increase the risk of having a heart attack, or myocardial infarction (MI).

While these cardiovascular conditions associated with the use of Avandia and Actos continue to receive most of the attention, there are some other serious side effects that have been linked to these diabetes drugs.

We start with a December 9, 2008 USA TODAY article, "Diabetes drugs double women's fracture risk"":

According to researchers at Wake Forest University School of Medicine who reviewed 10 previous drug trials, for every 20 women in their 70s with type 2 diabetes who took thiazolidinediones — rosiglitgizone (brand name Avandia) and pioglitazone (brand name Actos) — for at least one year, one of them has a chance of suffering a fracture. In women in their mid-50s, the figure equals one fracture in every 55 women. That's more than double the normal risk for those age groups.

The new research appears online in the Canadian Medical Association Journal this week. About 14,000 patients were involved in the studies analyzed by study co-author Sonal Singh, assistant professor of internal medicine at Wake Forest, and his colleagues.

The same increase in fractures was not found in men, says Singh, though the reason why was not determined.

The significance of this research is that while scientists already knew that thiazolidinedione (TZD) drugs for diabetes were associated with fractures, the magnitude of the risk had not been evaluated previously.  This Wake Forest study shows that Avandia and Actos double the risk of fractures in women with type 2 diabetes.

We move next to a press release that was issued earlier today, "Diabetes drug class linked to vision-threatening complication":

Treatment with the glitazone class of diabetes drugs leads to a "modest" increase in the risk of diabetic macular edema (DME)—a common complication that can lead to vision loss, reports a study in the April issue of the American Journal of Ophthalmology....

.... Diabetic macular edema is a common diabetes complication, with swelling and fluid build-up in the retina leading to progressive visual loss.

The researchers identified 996 patients who were diagnosed with DME during 2006. Overall, patients who took glitazones were 2.6 times more likely to develop DME than patients not taking these drugs. Even after further adjustment for other factors, DME risk remained 60 percent higher for glitazone users.

.... Most of the glitazone users in the study were taking pioglitazone (Actos). Other studies have linked rosiglitazone (Avandia)—the only other approved glitazone drug—to a possible increase in the risk of myocardial infarction.

The April 2, 2009 press release goes on to note that although this study is not the first study to suggest a link between the glitazone class of diabetes drug and the DME eye side effect, it provides confirmation in a very large sample of diabetic patients.

We will continue to monitor the safety profile of Avandia for further developments.