The Government Accountability Office (GAO) issued its final report(PDF) on the OCI this week and it is clear that accountability is the magic word. Specifically, the Office of Criminal Investigations lacks accountability to the FDA itself! Senior FDA officials never hear about OCI investigations unless the director of the department decides to share it. Can you imagine telling your boss “none of your business” if she asks about the specifics of a project you are working on? You would be undoubtedly be fired. Yet this is what the Office of Criminal Investigations can say to the FDA. According to the report, the FDA doesn’t have any requirements that the OCI report any specific information about their current investigations. On top of that, the FDA has an internal investigations unit called the Office of Internal Affairs (OIA). The OIA is an office within the OCI that investigates FDA employee misconduct. The OIA is not required to report specific information to OCI or any other FDA senior-level office. In addition, there is no process in place to ensure compliance with policies that guide investigations. In other words, the Office of Criminal Investigations and Office of Internal Affairs operates with little accountability to the FDA…let alone the American people.

The FDA responded to the report in a letter(PDF) to Senator Grassley (R-Iowa). The FDA’s letter highlighted reforms to deal with the shortcomings pointed out in the GAO report. The FDA highlights successful prosecutions since the start of the Office of Criminal Investigations in 1992. Well, its great to throw counterfeit drug makers and people who send contaminated products out into the market but what about the corporate officials responsible for hiding key safety data? The FDA plans to increase the use of misdemeanor* prosecutions to punish those officials. Of greater importance is the FDA’s commitment to develop procedures to disqualify certain clinical trial investigators from participating in the drug approval process. This is something that will be addressed in a post sometime in the near future but its important to mention that the FDA does not conduct its own studies. The FDA relies mostly on clinical trial data from the drug company to prove that the company’s drug is safe and effective. Disqualifying certain clinical trial investigators from submitting data is, in my opinion, one of the most important reforms that the FDA can make.

*misdemeanors are those crimes generally punished with fines.

**Repost from www.MarkSadaka.com

The following is the joint press release issued by Senators Max Baucus(D) and Chuck Grassley(R):

United States Senate
Committee on Finance
Washington, D.C.

For Immediate Release Saturday, February 20, 2010

Baucus, Grassley Release Finance Committee Report on Diabetes Drug Avandia, Express Concern About FDA’s Role in Protecting Patients in Ongoing Avandia Study

WASHINGTON – Senator Max Baucus, Chairman of the Committee on Finance, and Senator Chuck Grassley, Ranking Member, today released a committee report based on a two- year inquiry of the diabetes drug Avandia. The senators also asked the Food and Drug Administration to describe what steps the agency has taken to protect patients in an ongoing Avandia clinical trial, and why the study is allowed to continue, given that the FDA itself estimated that the drug caused approximately 83,000 excess heart attacks between 1999 and 2007. In 2008, FDA officials called the clinical trial, as then-designed, “unethical and exploitative” of patients.

“There’s a real problem when FDA’s office that reviews drugs that are on the market is an unequal player in drug safety efforts,” Grassley said. “It doesn’t make any sense to have these experts, who study drugs after they have been on the market for several years, under the thumb of the officials who approved the drug in the first place and have a natural interest in defending that decision. The Avandia case may be the most alarming example of the problem with this set-up. Both the FDA and Congress need to take every step possible to establish independence for post-market surveillance. The Institute of Medicine has made recommendations. It’s a matter of sound science and public safety.”

“Americans have a right to know there are serious health risks associated with Avandia and GlaxoSmithKline had a responsibility to tell them. Patients trust drug companies with their health and their lives and GlaxoSmithKline abused that trust,” Baucus said. “We will continue watching closely and working with the FDA to make sure patients and doctors are aware of the risks associated with Avandia and all drugs so they can make safe and informed decisions when choosing their medicines.”

The committee report explores when the Avandia manufacturer, GlaxoSmithKline, became aware of heart attack risks associated with the drug, whether the company sufficiently warned patients and the FDA of the dangers, and steps the company apparently took to create doubt regarding negative findings about the drug.

The report was developed over the last two years by committee investigators who reviewed more than 250,000 pages of documents provided by GlaxoSmithKline, the FDA, and several research institutes. Committee investigators also conducted numerous interviews and phone calls with GlaxoSmithKline, the FDA and anonymous whistleblowers. The report can be found at finance.senate.gov.

Baucus and Grassley directed the report over concerns that Avandia and other high- profile drugs such as Vioxx put public safety at risk because the FDA has been too cozy with drug makers and has been regularly outmaneuvered by companies that have a financial interest in downplaying or under-exploring potential safety risks. In 2007, Congress enacted legislation giving the FDA some new tools to better protect patients from harm caused by drugs that are brought to market without sufficient safety oversight or consumer warnings. However, the legislation did not fix a fundamental problem at the FDA — the imbalance between the office responsible for monitoring the safety of drugs after approval and the office that puts drugs on the market in the first place.

The FDA has overlooked or overridden safety concerns cited by its own officials, as appears to be the case with the ongoing Avandia study. The text of the Baucus-Grassley letter to the FDA on the Avandia study follows here.

February 18, 2010

The Honorable Margaret A. Hamburg, MD 
Commissioner 
U.S. Food and Drug Administration 
White Oak Building 1 
10903 New Hampshire Avenue 
Silver Spring, MD 20993

Dear Commissioner Hamburg:

As senior members of the United States Senate and Chairman and Ranking Member of the Committee on Finance (Committee), we have a duty under the Constitution to conduct oversight into the actions of executive branch agencies, including the Food and Drug Administration (FDA). In this capacity, we must ensure that FDA properly fulfill their mission to advance the public’s welfare, safeguard the nation’s drug supply, and protect patients participating in clinical trials.

We recently released a report raising concerns about Avandia, a diabetes drug made by GlaxoSmithKline (GSK). We began this inquiry after the New England Journal of Medicine published a study in May 2007 warning of the possible cardiovascular risk of Avandia.

Our report was based on a review of hundreds of thousands of pages of internal GSK documents and concluded:

The totality of evidence suggests that GSK was aware of the possible cardiac risks associated with Avandia years before such evidence became public…. Based on this knowledge, GSK had a duty to sufficiently warn patients and the FDA of its concerns in a timely manner. Instead, GSK executives intimidated independent physicians, focused on strategies to minimize findings that Avandia may increase cardiovascular risk, and sought ways to downplay findings that the rival drug ACTOS (pioglitazone) might reduce cardiovascular risk.

In 2007, the FDA asked GSK to perform a cardiovascular safety trial, called TIDE (Thiazolidinedione Intervention With Vitamin D Evaluation), to compare Avandia to other diabetes treatments such as ACTOS (piolglitazone). According to clinicaltrials.gov, the TIDE trial is currently recruiting patients. [ATTACHMENT A]

In response to several document requests made to the FDA, we received and reviewed an analysis conducted by two FDA safety officials. It is our understanding that this analysis, conducted in October 2008, reviewed all available studies comparing rosiglitazone (Avandia) to pioglitazone (ACTOS). The analysis by these FDA officials raise some alarms. For instance, they wrote:

[T]here is no evidence that rosiglitazone confers any unique health benefits over pioglitazone while there is strong evidence that rosiglitazone confers an increased risk of [heart attacks] and heart failure compared to pioglitazone. [ATTACHMENT B]

Even more alarming, they concluded that “any proposed head-to-head trial of rosiglitazone vs. pioglitazone would be unethical and exploitative.”

Two days after releasing this analysis, one of these same safety officers reviewed the protocol for the TIDE trial. This safety officer wrote that because of cardiovascular concerns with Avandia “the safety of the study itself cannot be assured, and is not acceptable.” [ATTACHMENT C]

After reading these documents, we would like to know what steps the FDA has taken to protect patients in the TIDE trial, and why this trial is allowed to continue. We would also like to know if the Office for Human Research Protection (OHRP) was notified about the safety concerns of the TIDE trial identified by the FDA. Further, we were alarmed to learn that the warnings from these safety officers do not appear to be addressed in the consent form that was handed out to patients that were enrolled in the study. [ATTACHMENT D]

We look forward to hearing from you by no later than March 4, 2010. Sincerely,

Max Baucus Chairman

Chuck Grassley Ranking Member

*Repost from www.MarkSadaka.com

I sat down on Saturday morning with my coffee and New York Times and right on the front page was an article that should have shocked me but didn’t. The article on the front page described a “fierce debate within the [FDA]” concerning whether or not the prescription drug Avandia is safe. For those of you that don’t know, Avandia is a drug used to treat type 2 diabetes by lowering the amount of sugar in the blood. According to the article, there seems to be some sort of civil war within the FDA where one faction wants to recall Avandia and another that thinks the drug should remain on the market.

Type 2 diabetics already have an increased risk of developing cardiovascular disease. Avandia received black box warnings about the increased risk of heart attack 8 years after it was approved in 1999. That is 8 years of type 2 diabetics suffering from deadly heart attacks that may have been prevented if they never received Avandia. The question is why would the FDA allow this drug to remain on the market when it increases the risk of heart attack in an already susceptible population? Nobody seems to know the answer to this question. Avandia is not unique and, as the New York Times article reports, there is a drug within the same family called Actos that seems to have better safety record.

Is there any good news from this? Yes. The good news is that because of this controversy doctors started to abandon the product. I am sure that more people will stop using Avandia after this article on the front page of the New York Times. The bad news is that more people will die while the FDA engages in a “fierce debate” with itself. More bungling from an agency charged with keeping us all safe from the bottom line interests of large corporations.

*This is a repost from Mark Sadaka’s blog (www.MarkSadaka.com)

April 2, 2009

The Honorable Barack H. Obama
President of the United States
1600 Pennsylvania Avenue NW
Washington, DC 20500

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.

On Monday, March 30, 2009, Dr. Joshua Sharfstein, newly appointed Principal Deputy Commissioner, assumed the position of Acting Commissioner until Dr. Margaret Hamburg is confirmed. Numerous FDA physicians and scientists are certain that Dr. Hamburg and Dr. Sharfstein will bring the necessary change to FDA to guarantee integrity, accountability, and transparency, to ensure that all future decisions are solely based on science and in accordance with the laws, rules, and regulations. However, sweeping measures are needed to end the systemic corruption and wrongdoing that permeates all levels of FDA and has plagued the Agency far too
long.

The latest example of wrongdoing was reported on March 23, 2009 from a Federal District Court Judge who ruled that FDA’s decision on the Plan B drug1 was “arbitrary and capricious because they were not the result of reasoned and good faith agency decision-making.” FDA’s top leaders at the Center for Drug Evaluation and Research (CDER) testified that they “didn’t have a choice, and . . .
[weren’t] sure that [they] would be allowed to remain [in their positions if they] didn’t agree” to ignore the science and the law. To the contrary, they should be removed from their positions of authority precisely because they didn’t follow the science and the law. The judge further ruled that there was “unrebutted evidence that the FDA’s [decision] stemmed from political pressure rather than permissible health and safety concerns.” The “improper political influence” and the many “departures from its own policies” reveal that such FDA officials are incapable of ensuring integrity and science at FDA.

On October 14, 2008, FDA physicians and scientists wrote to members of the House Energy and Commerce Committee reporting that top FDA officials at the Center for Devices and Radiological Health (CDRH) had distorted the scientific review of medical devices and then retaliated against those who brought this to light.2 Congressman John Dingell (then Chairman) and Congressman Bart Stupak (Chairman, Subcommittee on Oversight and Investigations) wrote to then FDA Commissioner Dr. Andrew C. von Eschenbach (since resigned), stating that there were “well-documented allegations that senior managers within CDRH” had “acted in violation of the law … [and that] sweeping measures may be necessary to address the distortion of science alleged by so many CDRH scientists.”3

On January 7, 2009, FDA physicians and scientists wrote to Mr. John Podesta4: “Through this letter and your action, we hope that future FDA employees will not experience the same frustration and anxiety that we have experienced for more than a year at the hands of FDA managers because we are committed to public integrity and were willing to speak out. Currently, there is an atmosphere at FDA in which the honest employee fears the dishonest employee, and not the other way around.
Disturbingly, the atmosphere does not yet exist at FDA where honest employees committed to integrity and the FDA mission can act without fear of reprisal. … America urgently needs change at FDA because FDA is fundamentally broken, failing to fulfill its mission, and because re- establishing a proper and effectively functioning FDA is vital to the physical and economic health of
the nation.”5

On January 13, 2009, the NY Times6 reported that FDA officials allowed “improper political influence”7 to guide official FDA actions. The Director of the Office of Device Evaluation, Dr. Donna-Bea Tillman, approved8 a medical device used for the detection of breast cancer despite the fact that all of the FDA experts involved recommended against approval of the device three times. Dr. Tillman’s decision to overrule the FDA experts “followed a phone call from a Connecticut congressman [Christopher Shays].”

On January 26, 2009, FDA physicians and scientists wrote to you directly9 seeking your help and recommending that “you remove and hold accountable all managers who have ordered, participated in, fostered or tolerated the well-documented corruption, wrongdoing and retaliation at the Agency.” That letter was prompted by concerns that FDA officials were planning to investigate physicians and scientists in retaliation for the January 13, 2009 story in the NY Times. These concerns were well-
founded.

On March 13, 2009, one week after another episode detailing wrongdoing and improper political influence involving top FDA officials was published in the Wall Street Journal,10 Acting Commissioner Dr. Frank M. Torti and FDA attorneys sprung into action. Their solution— send an FDA-wide email11 admonishing FDA employees that they “must comply with … obligations to keep certain information … confidential … [including] e-mail to and from employees within FDA [that document the] deliberative process” and threatening that “violation … can result in disciplinary sanctions and/or individual criminal liability.”

These threats did not escape the scrutiny of Senator Chuck Grassley,12 Ranking Member of the U.S. Senate Committee on Finance. In a letter to Dr. Torti on March 24, 2009, Senator Grassley wrote:
“Your memorandum … appears to run contrary to many statutes protecting executive branch communications with members of Congress. … I am concerned with the timing of your memorandum, given some recent high profile matters concerning your Agency and the release of information that has shown failures in FDA’s regulatory mission. [This] could be viewed … as an effort to chill and/or prevent FDA employees from exercising their rights under whistleblower protection laws. … Whistleblowers are some of the most patriotic people I know—men and women who labor, often anonymously, to let Congress and the American people know when the Government isn’t working so we can fix it.”

The Wall Street Journal13 and FDA documents14 revealed efforts by top FDA officials (including Dr. von Eschenbach, Dr. Torti, Mr. William McConagha, and other FDA attorneys) to cover-up their attempts to improperly influence, obstruct, impede and distort the due and proper administration of the FDA scientific regulatory process involving a knee implant device. According to the Columbia
University Journalism Review,15 “the [Wall Street] Journal describes a process in this case that’s, well, corrupt. I don’t know what else you’d call it. It even has a smoking gun.”16 An advisory committee of outside experts, convened to provide advice on the safety and effectiveness of the knee implant, was misled and manipulated by Dr. Daniel Schultz (Director of CDRH) as well as top FDA attorneys. Dr. Schultz was accused of “stacking the committee to get the decision the company wanted,” and of falsely stating in an official document that the conclusions reached by the advisory committee were “clear” and “unanimous”—to the contrary, they were not. A letter17 from Senator Grassley to Dr. Torti dated March 6, 2009 indicated that Dr. Schultz and top FDA attorneys had concealed the fact that two of the authors of a major publication presented to the advisory committee in support of the knee implant device, had affiliations with the device manufacturer (“the first author of the article is [the manufacturer’s] Vice President of Scientific Affairs,” Senator Grassley noted). Dr. Jay Mabrey, Chief of orthopedic surgery at Baylor University Medical Center in Dallas and Chairman of the advisory committee, should be commended for his integrity and willingness to speak out once he became aware of what had transpired. Dr. Larry Kessler, former Director of the Office of Science and Engineering Laboratories at FDA, who had direct knowledge of the advisory committee meeting and process, characterized the process as “show[ing] the FDA at its worst.”

The culture of wrongdoing and cover-up is nothing new but is part of a longstanding pattern of behavior. For example, in July 2005,18 Dr. Daniel Schultz “approved a medical device against the unanimous opinion of his scientific staff,”19 overruling “more than twenty FDA scientists, medical officers and management staff.”20 According to the New York Times21, the decision represented the first time in the agency’s history that a director “approved a device in the face of unanimous opposition from staff scientists and administrators beneath him.” As described in a Senate Finance Committee report following an investigation led by Senator Grassley,22 Dr. Schultz never revealed to the public that the FDA scientists, medical officers, and all other staff involved, completely
disagreed with his decision. The report also stated that “what remains the same in FDA’s approval of a device or a drug is the requirement that data supporting a sponsor’s application for approval be scientifically sound. Otherwise health care providers and insurers as well as patients may question the integrity and reliability of the FDA’s assessment of the safety and effectiveness of an approved product.”– We completely agree.

Amazingly, just 3 weeks ago, on March 6, 2009, it was reported by the consumer advocacy organization Public Citizen that Dr. Tillman “approved a [medical] device that has failed to demonstrate any clinical benefit” and that showed “trends toward higher risks of death.”23 According to Public Citizen: The March 6, 2009 approval by Dr. Tillman24 “bears an eerie resemblance to another device, Intergel, an anti-scarring device intended for pelvic surgeries that also demonstrated reduced scarring without clinically validated outcomes. … Less than two years after Intergel was approved [by Dr. Schultz25], the company removed the product from the market26 due to reports of post-operative pain, foreign body reactions and tissue scarring requiring repeat surgery, including three deaths among women who received it. This history should have given the FDA pause before once again approving a similar device with a questionable safety record.”27

But now, things may finally change at FDA and meeting the expectations of the public may become a reality. On March 14, 2009, an FDA-wide e-mail was sent from the Acting Secretary of HHS:
“Dr. Margaret “Peggy” Hamburg will be nominated by the President to serve as the next Commissioner and Dr. Joshua “Josh” Sharfstein will serve as the Principal Deputy Commissioner of the FDA. … The FDA is the premier agency of its kind in the world, and President Obama wants to revitalize the agency and empower it to make the best possible decisions for the American people based on the best science available. Dr. Hamburg and Dr. Sharfstein will work hard to support scientific integrity at FDA, strengthening the ability of the agency’s professionals to do their work on behalf of the American people. They are the perfect people to translate the President’s vision for the FDA into reality.”

We share your vision and we urge that you provide all necessary support to enable your new leadership to bring change to FDA without delay as part of your planned healthcare reform. As stated in a recent NY Times editorial, you must “send a clear signal to the bureaucracy that the days of neglect are over. Officials [must] make clear that the … practice of distorting science and weakening regulation to favor industry also is over.”28 – We completely agree.

FDA must carry out its work in a transparent manner based on sound science in order to improve the lives of all Americans, reduce health care costs, and expand health care access. Much work remains to be done at FDA and all pending matters need to be addressed. The wrongdoing revealed in the Wall Street Journal involves top FDA officials and requires immediate investigation. Astoundingly, since May 2008,29 Dr. von Eschenbach, Dr. Torti, Mr. McConagha, and numerous top FDA officials, have been well-aware of other serious wrongdoing, and failed to take any actions, while the physicians and scientists who spoke out and refused to comply have suffered retaliation.

The clearance/approval of medical devices that were not made in accordance with the laws, rules and regulations, need to be re-visited. Furthermore, those FDA employees who have engaged in wrongdoing, who have violated laws, rules, and regulations, who have abused their power and authority, and/or who have engaged in retaliation, should be dealt with swiftly. Immediate and decisive disciplinary action will send a strong message FDA-wide that wrongdoing will no longer be tolerated and those who engage in wrongdoing will be held accountable. Some wrongdoing may be beyond the scope of FDA’s jurisdiction and may need referral to the U.S. Attorney General.

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 have their professional lives restored. We ask that you accept nothing less.

Sincerely,

[Names Redacted]

Click here for a copy of the Original Letter

Based on current information, fruit from this company appears to be associated with a Salmonella Litchfield outbreak in the United States and Canada.

To date, FDA has received reports of 50 illnesses in 16 states and nine illnesses in Canada linked to eating cantaloupes. The states are Arizona, California, Colorado, Georgia, Illinois, Missouri, New Jersey, New Mexico, New York, Ohio, Oklahoma, Oregon, Tennessee, Utah, Washington, and Wisconsin. No deaths have been reported; however, 14 people have been hospitalized.
Symptoms of Foodborne Salmonella Infection

Symptoms include nausea, vomiting, fever, diarrhea, and stomach cramps. In individuals with poor health or weakened immune systems, Salmonella can invade the bloodstream and cause life-threatening infections. Individuals who have recently eaten cantaloupe and experienced any of these symptoms should contact their health care professional.
Tips for Consumers

To reduce the risk of getting Salmonella or other foodborne illnesses from cantaloupes:

Buy cantaloupes that are not bruised or damaged. If buying fresh-cut cantaloupe, be sure it is refrigerated or surrounded by ice.

After purchase, refrigerate cantaloupes promptly.

Wash hands with hot, soapy water before and after handling fresh cantaloupes.

Scrub whole cantaloupes by using a clean produce brush and cool tap water immediately before eating. Don’t use soap or detergents.

Use clean cutting surfaces and utensils when cutting cantaloupes. Wash cutting boards, countertops, dishes, and utensils with hot water and soap between the preparation of raw meat, poultry, or seafood and the preparation of cantaloupe.

If there is a bruised or damaged area on a cantaloupe, cut away that area before eating.

Throw away any leftover cut cantaloupe if it’s left at room temperature for more than two hours.

Use a cooler with ice or use ice gel packs when transporting or storing cantaloupes outdoors.

When it comes to notorious Bush political appointees, Daniel Troy’s name doesn’t usually make the top-10 list, overshadowed as he is by more high profile cronies such as FEMA’s Michael Brown. But for three years in the president’s first term, Troy served as the chief counsel to the Food and Drug Administration (FDA), where he quietly advanced a legal revolution that is playing out in earnest in the U.S. Supreme Court this year. This revolution has the potential to affect the health and safety of the nation’s citizens for years to come, all while making Troy a rich man. In fact, his career is an illustration of how the Bush administration’s revolving door has allowed industry lawyers to radically reshape regulatory agencies to benefit the big businesses they once represented and then profit from those changes when they return to the private sector.

Learn More:  Mother Jones

It is important to interpret these preliminary results with caution. FDA is working with Boehringer Ingelheim to further evaluate the potential association between Spiriva and stroke. FDA has not confirmed these analyses and while pooled analyses can provide early information about potential safety issues, these analyses have inherent limitations and uncertainty that require further investigation using other data sources. Patients should not stop taking Spiriva HandiHaler before talking to their doctor, if they have questions about this new information.

This is an important step forward in the FDA’s plans to hire and place FDA staff in China over the next 18 months. In addition, the FDA will be hiring a total of five local Chinese nationals to work with the new FDA staff at the U.S. Embassy in Beijing and the U.S. Consulates General in Shanghai and Guangzhou.

“In an age when a border is not a barrier, the globalized economy demands nothing less than heightened regulatory interoperability, information exchange, and cooperation, especially on product quality and enforcement matters,” said Murray M. Lumpkin, M.D., deputy commissioner for International and Special Programs, FDA. “Along with the important Memoranda of Agreement signed with two FDA counterpart Chinese agencies, our efforts to fill permanent FDA positions in China are a significant step toward ensuring access to safe food, drugs, and medical devices in the global market.”

Building the FDA’s capacity outside of the United States supports the agency’s “Beyond our Borders” initiative. The initiative facilitates the building of stronger cooperative relationships with the FDA’s counterpart agencies around the world and enhanced technical cooperation with foreign regulators. The permanent overseas offices in China will also allow greater access for inspections and greater interactions with manufacturers to help assure that products that are shipped to the United States meet U.S. standards for safety and manufacturing quality.