Both sides of Capitol Hill are asking questions about the unexpected departure of FDA Commissioner Dr. Lester Crawford. 

Crawford stepped down from the FDA’s top post on September 23rd, just two months after a heated confirmation battle in the Senate.  He told Forbes.com that he decided to leave the FDA because he was tiring after three years at the agency, but other reports have suggested that Dr. Crawford left due to potential conflicts of interest from his financial holdings.

In a letter sent yesterday to Daniel Levinson, Inspector General of the Department of Health and Human Resources, Senators Michael Enzi(R-WY) and Edward Kennedy (D-MA) requested a thorough review of the reasons surrounding Dr. Crawford’s resignation.  They asked  the Inspector General to  specifically “examine his financial reporting in accordance with various ethics laws to determine whether he was in compliance and whether he was forthcoming” with the Committee.

Enzi is the Chairman of the Health, Education, Labor and Pensions Committee, and Kennedy is the Committee’s ranking Democrat.

They also requested information concerning any dates during which Crawford’s financial holdings may have posed conflicts of interest, and asked for specifics on what decisions he made during those times.

“The FDA is one of this country’s most important agencies.  The nation must have complete confidence that FDA is led by a fully vetted Commissioner, free from conflicts of interest,” wrote Enzi and Kennedy.

A similar effort has come from the House of Representatives.  Congressman Maurice Hinchey (D-NY), along with five of his House colleagues, also called on the Department of Health and Human Services Inspector General to examine the reasons for Crawford’s surprise resignation.

In a letter dated September 28th, they wrote: “We believe that the sudden nature of this action, combined with both conflicting reports about the resignation and recent difficulties at the FDA, warrant your office’s involvement in this matter. Congress and the public deserve to know what is going on with the leadership at the Food and Drug Administration.”

There will definitely be another influenza pandemic and no government can afford to be caught off-guard, according to World Health Organization (WHO) Director-General Dr. Lee Jong-wook.

Speaking to ministers of health from throughout the Americas at the Pan American Health Organization’s 46th Directing Council meeting on Tuesday, Dr. Jong-wook cautioned that “forecasts indicate that the political, social and economic costs of such a pandemic will be huge.  Failure to take the threat seriously and prepare appropriately will have catastrophic consequences.”

He called on health ministers to support the International Partnership on Avian and Pandemic Influenza launched recently by President George Bush at the United Nations.  “Every country must have a national pandemic control plan.  Every country must also have a communications strategy.  It should be ready and able to inform the public about the pandemic, what is happening and what to do,” he said.

Dr. Jong-wook cited past flu epidemics that killed millions of people and noted that the 1957 and 1968 flu pandemics “originated as avian flu viruses.”  There have been outbreaks of the H5N1 avian flu in Asia since 2003 and the World Health Organization warns that the virus could change into a form that spreads easily from person to person.  As people would have no natural immunity, a new influenza virus could cause widespread death, illness, social and economic disruption.

The United Nations Secretary General has appointed Dr. David Nabarro, a senior public health expert at the World Health Organization, to lead coordination of the UN response to avian influenza and a possible human influenza pandemic.  He will be responsible for ensuring that the UN moves forward with efforts to control the current outbreak of avian influenza in Asia, and he will help to coordinate preparations for a potential human influenza pandemic.

Senate Majority Leader Bill Frist (R-TN) and Senate Democratic Leader Harry Reid (D-NV) both spoke on the Senate floor Wednesday about the potential pandemic.  Senator Frist, a medical doctor, cautioned “Experts warn that a global, cataclysmic pandemic is not a question of if, but when.  Like an earthquake, it could hit anytime.  And when it does, it could take the lives of tens of millions of people – including half a million people right here in the United States.  The threat is real.”

Dr. Frist went on to say “We need a coordinated, comprehensive, and aggressive plan which draws on public health, homeland security, foreign policy and defense expertise.”  He has called for a “Manhattan Project for the 21st Century” which would launch an unprecedented collaboration between government, industry, and academia.

Senator Reid said that the time to prepare for the flu pandemic is now.  He explained “A flu pandemic occurs when a new strain of flu emerges in the human population that can cause serious illness and death and can easily spread between humans.  The avian flu referred to by scientists as the H5N1 flu strain already meets the first test.  Roughly half of the 115 people who have been diagnosed with the virus have died. 

“At present, all that stands between avian flu and pandemic status is the fact that scientists do not believe avian flu can be transmitted between humans.  All known cases have been the result of transmission from birds to humans.  However, scientists fear that it is only a matter of time before the avian flu virus mutates into a form that can spread easily from human to human.”

Senator Reid reported that a respected U.S. health expert had concluded that 1.7 million Americans would die in the first year alone of an outbreak and that a pandemic in the United States would cost the economy hundreds of billions of dollars.  He said that neither the United States nor the world was prepared to deal with a flu pandemic, and that the World Health Organization “has recommended that countries stockpile enough anti-viral medication to cover 25 percent of their populations.”

While many countries, including Great Britain, France, and New Zealand have ordered enough Tamiflu, an antiviral pill, to cover up to 40% of their population, Senator Reid said that “we have been told that the United States would have to wait until the end of 2007 before we could secure enough Tamiflu to cover just 25 percent of our population.”

Senator Reid said immediate action should take place on several fronts:

·    Improve surveillance and international partnerships so new flu strains can be detected early
·    Finalize and fund pandemic preparedness and response plans
·    Develop, produce, and distribute an effective vaccine
·    Stockpile antiviral medications
·    Educate Americans about pandemic flu

Senator Reid ended by saying that action needs to be taken now.  “We need not wait for a perfect plan on paper to start dedicating more resources to address this issue.  We know today that funding certain programs can dramatically reduce the consequences of a future avian flu outbreak.  We also know that many of these programs are either unfunded or massively under funded.”

The Senator, along with colleagues, introduced an amendment to the Defense Appropriations Bill that would provide $3.913 billion to the Centers for Disease Control and Prevention (CDC).  The money would be used for the stockpiling of antiviral medications and necessary medical supplies, global surveillance; increased vaccine capacity, and grants to state and local public health agencies for emergency preparedness.

Frederick “Mike” Humeston, a 60-year-old Idaho postal worker who suffered a heart attack while taking Vioxx, is suing Merck, contending that the drug maker hid Vioxx’s risks in an effort to preserve sales. 

He took the stand Wednesday in the third week of the New Jersey Vioxx trial.

Mr. Humeston stated that he had been in good health prior to his heart attack, and had turned to Vioxx to relieve pain from an old Vietnam War wound.  He had taken the medication for about two months when he suffered a debilitating heart attack while sitting in an easy chair.

The plaintiff described the radical changes in his life after the heart attack, detailing a list of activities that he could no longer perform.  Humeston said that his September 18, 2001 heart attack had even affected his relationship with his wife.

Merck withdrew Vioxx from the market in 2004 after studies showed that it raised the incidence of heart attacks and strokes. In the first Vioxx trial, a Texas jury awarded $253 million to the widow of a Vioxx user.  Merck is appealing that decision, and has promised to fight each Vioxx case individually.  However, analysts contend the company could face very significant legal liabilities and may have to consider a broad settlement if they continue to lose cases.

Before Mr. Humeston’s testimony, Merck lawyers asked Superior Court Judge Carol Higbee to either declare a mistrial or strike the testimony of a prosecution witness, statistician Richard Kronmal.  Merck contends that Mr. Kronmal’s testimony unfairly inflamed the jury.  The judge did not immediately rule on the request.

Eli Lilly & Company is warning that its ADHD drug, Straterra, may cause suicidal thoughts in children and adolescents. 

In a press release dated today, Lilly reported that its Straterra clinical trials database had identified a small but statistically significant increased risk of suicidal thoughts among Straterra-treated children and adolescents.  Out of 1357 children, there were five reported cases of suicidal thoughts, versus none in a group of 851 patients taking a placebo.

While there was also one case of a suicide attempt in the 1357 patients, no deaths were reported, and there was no indication of an increased risk of suicidal thinking in the adult population. 

The FDA has an ongoing review of psychiatric medicines, and requested the clinical trial data from Lilly.  The analysis of the data was based on criteria developed by Columbia University and the FDA last year.

Dr. Alan Brier, chief medical officer at Lilly said “While suicidal thinking was uncommon in patients on the medication during clinical trials, it is important for parents to be aware it can occur, and to discuss any unusual symptoms with a physician.”

ADHD affects between three and seven percent of school-age children, and about four percent of adults in the United States.  Symptoms include distractibility, impulsivity, and a lack of attention and concentration.  

According to a recent Center for Disease Control (CDC) study, ADHD is diagnosed more often in boys, and is diagnosed less often in minority children.  A report published by the Consumers Union finds that while stimulant drugs are effective, they are probably being prescribed to many children who do not have the disorder.

Lilly plans to add a boxed warning to the product label and is working with the FDA to finalize the updated information that it will send to healthcare professionals and world wide regulatory agencies.

Criminal investigators at the U.S. Food and Drug Administration have joined the agency’s probe into how Guidant Corporation handled problems with its heart devices, according to Thursday’s New York Times.

The FDA has been looking more closely at Guidant’s products, and recently completed an inspection of the company’s St. Paul, Minnesota Cardiac Rhythm Management facility.  That inspection led to a Class I recall of some of Guidant’s best-selling pacemakers. 

One aspect of interest to the FDA is whether Guidant properly reported device failures and manufacturing changes.  Executives of Guidant maintain that they properly reported all issues to the FDA.

FDA spokeswoman, Julie Zawisza, told the Times that the agency does not confirm or deny ongoing investigations, and a spokesman for Guidant, Steven Tragash, told the newspaper that he was not aware that the company had been contacted.  He added that the company was aware that some former employees had been contacted by the FDA.

Once the FDA completes its investigation, it can choose to forward its findings to the Justice Department, which can take a number of actions, including bringing civil or criminal charges against the company.

The FDA investigation is not Guidant’s only problem.   Both the New York Times and the Wall Street Journal reported on Tuesday that Guidant had paid doctors to implant its medical devices.  The Times said that Guidant had paid physicians $1,000 for implanting an improved electrical component, called a lead, into three patients.

Guidant stated that they ran programs like the electrical lead evaluation so they could improve future models.  However, according to the Times, critics of the industry have long charged that some companies use research studies to mask what are really marketing efforts.

The Times editorial page also weighed in on the issue of physician ties to medical device makers, stating that “many surgeons have ties to manufacturers, ties that are often not revealed to their patients or to hospitals.”  The editorial went on to say that while doctors maintain they need close relationships with manufacturers so they can help perfect medical devices, there are several ongoing investigations to determine if these consulting arrangements are in fact “unethical and unlawful payoffs for using the devices."

In the world of prescription drugs, Lipitor is the king with over $10 billion in annual sales.

Some consumer groups, however, believe that the drug’s manufacturer, Pfizer Inc., engaged in deceptive advertising of the cholesterol drug in order to boost sales.

Only one day after the Food and Drug Administration (FDA) approved the drug for additional populations, a federal class-action was filed in U.S. District Court in Boston, Massachusetts by Community Catalyst and Health Care For All claiming that Pfizer marketed Lipitor to reduce cholesterol in patient populations that had not been covered in clinical trials.

The suit also alleges that Pfizer engaged in a massive campaign to convince both doctors and patients that Lipitor is a useful treatment for nearly everyone with elevated cholesterol, even though no studies have shown it to be effective for women and those over 65 years of age who do not already have heart disease or diabetes.
In particular, the suit claims that Pfizer violated state consumer protection laws by promoting Lipitor as preventing heart disease in women or people over 65 who did not have heart disease and diabetes when it did not have studies to support such a claim.

 Pfizer, however, announced that the FDA approved the drug for patients with Type 2 diabetes and those without diabetes who did not have heart disease but who had one or more risk factors for the condition other than high cholesterol. These include high blood pressure, family history, being over 55, smoking, and obesity.

The approval was based on two clinical trials involving more than 13,000 patients, Pfizer said.
The plaintiffs allege that Pfizer’s advertising of the drug created billions of dollars in unnecessary drug spending among the two patient groups. They cited a study of 2,000 women, which concluded that those taking Lipitor actually suffered 10% more heart attacks than those taking a placebo.

The lawsuit seeks reimbursement for women and seniors and third-party payers who bought Lipitor "unnecessarily." Lipitor sales amounted to $10.86 billion in 2004, almost 21% Pfizer’s total revenue and, although it is not clear how much of that figure is attributable to the two groups that are the subjects of the class-action, damages could run into the billions if the suit is successful.

GlaxoSmithKline (GSK) and the Food and Drug Administration (FDA) notified physicians yesterday that PAXIL and PAXIL CR (paroxetine HCI) may be linked to a higher rate of birth defects than currently found with similar drugs.

GSK recently conducted a retrospective study of congenital malformations in babies born to 3,581 women taking antidepressants during the first trimester of pregnancy.  Preliminary results suggested an increase in the risks of congenital malformations associated with the use of PAXIL as compared to other antidepressants.  The malformations were usually cardiovascular, with the most common being ventricular septal defects. 

In a letter to healthcare professionals, GlaxoSmithKline noted that the retrospective study was designed to evaluate the relative risk of congenital defects in infants born to women who were taking antidepressants.  The study did not include a comparison to infants who were not exposed to antidepressants.

The British drug maker noted that a number of previous studies relating to first trimester exposure to antidepressants have been done since the late 90’s, with various conclusions.  The mixed results make it difficult to definitively conclude that paroxetine has a causal relationship to any particular congenital abnormality.

PAXIL currently carries a Category C pregnancy precaution on its label.  The precaution indicates that that no well-controlled human studies have been done on the effect of taking paroxetine during pregnancy.  Information concerning the new study will be added to the label.

GSK cautioned doctors to “carefully weigh the potential risks and benefits of using paroxetine therapy in women during pregnancy.”  They encouraged doctors to discuss the latest findings with their patients.

Users of the beta blocker TOPROL-XL, taken for the treatment of conditions such as hypertension and angina pectoris, need to insure that they are receiving the correct medicine from their doctors and pharmacists. 

The Food and Drug Administration (FDA), along with TOPROL-XL’s manufacturer, AstraZeneca, notified healthcare professionals and pharmacists this week that they had received reports of medication dispensing or prescribing errors.

TOPROL-XL is being confused with Topamax, indicated for the treatment of epilepsy and migraine prophylaxis, and Tegretol or Tegretol-XR, used for the treatment of seizures.  According to letters sent to healthcare professionals and pharmacists, AstraZeneca received reports that TOPROL-XL was incorrectly administered to patients instead of Topamax, Tegretol, or Tegretol-XR, and vice versa, some of them leading to adverse effects.

“Adverse effects have been reported to occur as a result of nonadministration of the intended medication and/or exposure to the wrong medication.  In some cases, hospitalization was required.  Examples of serious events reported…include recurrence of seizures; return of hallucinations; suicide attempt; and recurrence of hypertension.”

According to the letters, the medication error reports indicated that both verbal and written prescriptions were incorrectly interpreted and/or filled due to the similarity in names between the drugs. Additionally, overlapping strengths between TOPROL-XL and the other drugs, and the fact that they are stocked close to each other in a pharmacy, may have contributed to the errors.

The letters ask healthcare professionals to clearly communicate both oral and written prescriptions for TOPROL-XR, and requests that pharmacists arrange product inventory in a way that helps staff to differentiate between medicines, and to read labels several times to confirm that the correct medication is being dispensed.

The U.S. Consumer Product Safety Commission announced the recall of approximately 112,000 Automatic Defrost Upright Freezers and Refrigerators manufactured by WC Wood Company between September 2002 and February 2004. 

These units were sold at home improvement and appliance stores between September 2002 and February 2005.

The single-door frost-free upright freezers (15, 17 and 20 cubic feet) and all 17-cubic foot automatic defrost refrigerators pose a potential shock hazard to consumers.  The defrost heater coil in some units can become exposed, resulting in a shock hazard, and the exposed heater wire can also melt or burn the unit’s interior plastic food liner. 

WC Woods received 45 reports of incidents of the defrost heater coil being exposed.  None of these incidents resulted in an electrical shock and no injuries were reported.

These units were sold under the Amana, Crosley, Danby, Maytag, Whirlpool and Wood’s brands.  The freezers and refrigerators come in black, white, or stainless steel.  The brand name is written on the front of the unit.  The manufacturer’s label, with the model number and date of manufacture, is located inside the appliance on the front top left-hand corner.

The label names and model numbers involved in the recall are as follows:

·    Amana – Model Numbers beginning with: AFU1567, AFU1767, AFU2067
·    Crosley – Model Numbers beginning with: FFCR17, WCF15, WCF17, WCF20
·    Danby – Model Numbers beginning with: DUF1700, DFF1708
·    Maytag – Model Numbers beginning with: MQU1556, MQU2057
·    Whirlpool – Model Numbers beginning with: EV150NXM, EV170NYL, EV171NYM, EV200NXK, EV201NXM, EL7ATRRK, EL7ATRRM, EL7JWKLM, EL7JWKRM
·    Wood’s – Model Numbers beginning with: F15, F17, F20, F42, F47, F55, WFF15, WFF17, WFF20, RFA17, RFC17, R47F

Consumers should contact WC Wood at 866-493-3314 for a free in-home repair.

Are the scientists who recommend approval of drugs for public use too close to the pharmaceutical industry?  Some members of Congress would like to find out.

U.S. Senator Mike Enzi, R-WY, Chairman of the Senate Health, Education, Labor and Pensions Committee and Senator Edward M. Kennedy, D-MA, Ranking Member of the Committee, have asked the Government Accountability Office (GAO) to review the Food and Drug Administration’s practice of providing conflict of interest waivers to members of its scientific advisory committees.  Panel members on these committees are charged with recommending approval of drug and medical devices for public use.

Enzi and Kennedy were joined in the request by Senator Richard J. Durbin, D-IL.  Senator Durbin is the Assistant Democratic Leader.  In their letter, they say “We are concerned about the process that supports FDA’s decisions to waive conflict of interest rules for scientists with financial ties to the manufacturers of the products under consideration, or their competitors.”

Panel members are meant to provide the FDA with unbiased, independent, and professional advice.  They are required to be free of conflicts of interest concerning any products they recommend for approval.  However, the FDA can grant a waiver if they feel that an expert’s participation is necessary, the financial interests are so small so as not to affect the individual’s service, or if the need for the expertise outweighs the potential conflict due to financial interest.

In the letter to David M. Walker, the Comptroller General, the Senators lay out the FDA’s charter in regards to drug approval.  “The Food and Drug Administration (FDA) has the important responsibility of ensuring that the drugs, medical devices, vaccines, and other products used by the American people are safe and effective.  The scientific advisory committee system at the FDA is meant to provide the agency with unbiased, independent and professional advice on general scientific matters and issues related to the particular products or classes of products.  The scientific expertise provided by the advisory panels is critical to FDA’s ability to fulfill its mission of protecting public health.”

“We are concerned about allegations with regard to FDA’s use of waivers of the conflict of interest requirements,” the Senators continued.    They provided two examples of such potential conflicts of interest.  The first concerned the FDA’s advisory panel on the safety of Cox-2 inhibitors (such as Vioxx), where nearly one-third of the members received a waiver.  The second example described allegations currently under review that one member of a panel considering the safety of silicone-gel breast implants received payments (either directly or indirectly) from the device industry.

“These practices appear to have undermined the public’s faith in the objectivity and fairness of FDA’s advisory committees,” the letter stated.  “Further, there are questions about transparency in FDA’s procedures for forming advisory committees and granting waivers.” 

The Senators asked the GAO to examine the issue and address the following questions, among others:

·Has the proportion of waivers grown over the past decade?  How many of these waivers are for voting rather than non-voting panelists?

·What process exists for determining if a waiver should confer voting or non-voting status?

·Is there evidence that waivers influence voting?  For example, is a member with a financial interest more likely to vote for the product under review (or against it) than a member without a financial interest?

·FDA’s decision to grant a waiver is often based on the need for the individual’s expertise.  What barriers exist to identifying qualified individuals without conflicts?

·How does the FDA screen individuals it is considering for appointment to advisory committees for conflicts of interest?  What procedures does the FDA have in place for identifying alternative individuals with minimal or no potential conflicts?

·Are the agency’s current disclosure statements transparent and appropriately detailed?  How does FDA balance the needs for privacy and the requirements of FOIA (The Freedom of Information Act) versus the need for public disclosure of waiver agreements?

According to Craig Orfield, Spokesman for the Health, Education, Labor and Pensions Committee, the GAO generally takes several months to respond to a request of this type.  While no decision has been made to hold hearings on this topic, he left open that possibility.