Government Accountability Office Report Highly Critical of FDA Is Anything But News to Most Observers

By Steven DiJoseph

For years, critics of the FDA have claimed that suffers from a number of serious operational problems that have caused it to become an ineffective guardian of the public’s wellbeing and little more than a rubberstamp for the multi-billion-dollar pharmaceutical industry.

Those who have raised their voices against what they perceive as a bloated regulatory agency rife with mismanagement, internal strife, and conflicts of interest include members of Congress, highly-respected scientists and medical experts, FDA whistleblowers, and consumer advocacy groups.

Thus, when the Government Accountability Office (GAO) was asked by Congress to examine the FDA (following the debacle surrounding the withdrawal of the COX-2 inhibitor Vioxx); few expected anything but a laundry list of criticisms. The GAO did not disappoint. In fact, its report exceeded expectations for candor.

The findings made by the GAO included the following:

  • The FDA is often sluggish in acting upon safety problems with drugs that have already been approved.
  • Internal policies for assessing drug safety are inconsistent and often exclude the agency’s most qualified experts from the process.
  • The FDA should be given broader authority to compel drug companies to conduct post-approval studies that were agreed to as a condition of approval or that were in progress when approval was granted.
  • The FDA has dropped the ball with respect to the handling of a number of situations involving controversial drugs (especially Vioxx). The GAO concluded that these situations demonstrated “a lack of criteria for determining what safety actions to take and when to take them.”
  • The agency’s entire system for reviewing the safety of approved drugs is too limited and seriously flawed.
  • There are serious conflicts between the Office of Drug Safety and the Office of New Drugs. The former, while far smaller and not nearly as well-funded, is charged with monitoring potential safety risks as they develop. Although the office has many of the FDA’s best experts on drug safety, its recommendations are often ignored by the much larger Office of New Drugs which regularly excludes members of the Office of Drug Safety from pivotal committee meetings on the very drugs it has been studying. (This is especially true of researchers who have negative views with respect to the drug being considered or who are categorized as whistleblowers. Critics have often accused the Office of New Drugs of being little more than a rubberstamp for the drug industry which now funds more than half of the expense involved in evaluating New Drug Applications.)

Alastair Wood of Vanderbilt University, an important member of the FDA’s advisory panel on drug safety and risk management, stated that the GAO report “confirmed a lot of what people have been saying for some time. He added, however, that the FDA has failed to adopt a policy of taking decisive action to ensure drug safety. “Frankly, it doesn’t look right now as if much has changed.”

In previous articles we have reported on what critics of the FDA see as failures of drug approval process, post-approval monitoring, and supervision of direct-to-consumer advertising that have reduced the once highly respected agency to little more than a ‘paper tiger’

For example, in January a story was carried by hundreds of news outlets, including, of an eagerly awaited diabetes drug, nearing final approval by the FDA, which significantly increases the risk of heart attacks, strokes, or death, as reported by researchers in a study published in the Journal of the American Medical Association (JAMA).

Was this an example of an isolated incident of a potentially dangerous prescription drug “slipping through the cracks” in an otherwise secure drug approval process at a responsible federal agency? Hardly.

Instead, it was yet another situation that raises serious questions concerning the reliability of the FDA’s drug approval process and whether it is unduly biased in favor of the pharmaceutical industry.

It was what one pharmaceutical litigation expert we spoke with called an example of the “same old FDA whitewash.”

Muraglitazar, which would be marketed as Pargluva by Merck and Bristol-Myers Squib, was recommended for approval last month by an 8-1 FDA advisory committee vote.

Using the very same data the FDA panel and staff examined, however, the JAMA study researchers identified several extremely serious health concerns about the drug including almost a threefold greater risk of heart failure, heart attack, stroke, and death.

“Ten of 1,000 patients would die, have a heart attack or a stroke,” said lead author Steven Nissen of the Cleveland Clinic. “Those are serious irrevocable events.”

The alternative study came from the highly respected researchers at the Cleveland Clinic, the same team that broke the story on the cardiovascular dangers of Vioxx.

Dr. Nissen concluded that: “These findings are particularly concerning because the significant excess of adverse events was observed after only limited drug exposure ranging from 24 to 104 weeks,” Nissen and colleagues report. “Real-world exposure would likely substantially amplify the risk. Taken as a whole, these data demonstrate that [Pargluva], if approved by the FDA, would constitute an unacceptable patient hazard.”

One must wonder; how then did the FDA advisory committee that recommended the drug for approval by a vote of 8-1 ignore both the indisputable clinical data as well as the FDA’s own analysts who had themselves identified evidence of cardiac risk?

In a scenario similar to the Vioxx narrative, however, those analysts did not highlight this cardiac risk to patients as significant, except in cases where the drug was used in conjunction with other therapies.

Bristol-Myers concluded that there was no significant increase in heart risk for patients. The analogy to the Vioxx debacle is inescapable. (As Yogi Berra would say; “This is like deja vu all over again.”)

The Pargluva story is merely a small chapter in what critics see as the all too familiar scenario of a regulatory agency being influenced in its decision-making by the very industry it is supposed to be regulating.

This pattern is also seen as a symptom of a more serious disease, however, the premature approval and marketing of dangerous drugs which are ultimately found to pose far greater risks than any benefit they may have had.

Since the late 1990s, there has been a dramatic increase in the number of drugs that have had to be withdrawn from the market. The institution of an industry-funded “fast track” drug approval process has lead to inadequately tested drugs being rushed to market and the need for more and more serious (“black box”) warnings.

Between 1997 and the beginning of 2005, 19 drugs were withdrawn from the market. These include:

·        Palladone (hydromorphone) – 2005

·        Bextra (valdecoxib) – 2005

·        Tysabri (natalizumab) – 2005

·        Vioxx (rofecoxib) – 2004

·        Duragesic Patch (fentanyl transdermal patch) – 2004

·        Ephedra – 2004 (withdrawal order vacated by a federal judge)

·        Baycol (cerivastatin) – 2001

·        Raplon (rapacuronium bromide) – 2001

·        Rezulin (troglitazone) – 2000

·        Propulsid (cisapride) – 2000

·        Lotronex (alosetron) – 2000

·        Hismanal (astemizole) – 1999

·        Raxar (grepafloxacin) – 1999

·        Posicor (mibefradil) – 1998

·        Duract (bromfenac) – 1998

·        Seldane (terfenadine) – 1997

·        The Diet “Cocktail”: Fen-Phen (fenfluramine); Pondimim; and Redux (dexfenfluramine) – 1997

Once Vioxx was pulled from the market (on September 30, 2004) in the largest drug recall in history, a growing number of experts, elected officials, and public watchdog organizations began to raise serious questions about the FDA’s drug approval process.

It became obvious to those critics that the FDA was no longer capable of protecting the public from unsafe drugs and pharmaceutical company influences. In fact, the very integrity of the agency is now a legitimate concern since many medical professionals believe the FDA is currently biased in favor of the pharmaceutical industry.

In order to understand how the FDA’s credibility and integrity became so compromised it is necessary to look at the FDA drug approval process as well as the necessary steps and reasons for the removal of a drug from the market.

On November 18, 2004, a federal drug safety reviewer told a Congressional panel that the FDA is “virtually incapable of protecting America from unsafe drugs.” He accused the agency easily surrendering to the demands of pharmaceutical companies.

Dr. David Graham, an Associate Director for Science and Medicine in the FDA’s Office of Drug Safety is a scientist with impeccable credentials as well as a man of unchallenged integrity who has devoted his entire professional life to making a real difference in the cause of patient safety.

Although Dr. Graham fought long and hard against Vioxx based upon the overwhelming evidence of its serious cardiovascular risks, he was little more than “a voice crying in the wilderness” who received no support within the FDA.

On November 18, 2004, this public servant turned whistleblower appeared before the Senate Finance Committee Chaired by Sen. Charles Grassley (R-Iowa). Dr. Graham delivered stunning and often shocking testimony concerning the very real dangers of Vioxx and the unconscionable delay in pulling the drug from the market which has exposed the public to a degree of risk never before seen with respect to any prescription drug including sulfanilamide and thalidomide.


Dr. Graham presented the evidence against Vioxx in painstaking detail. He also set forth the disturbing facts surrounding the FDA’s efforts to suppress his research, censor and alter his scientific and medical findings and conclusions, and discredit his work.

The most striking portion of Dr. Graham’s testimony involved his carefully formulated opinion that (even using Merck’s own VIGOR and APPROVe trials) some 88,000 to 139,000 Americans alone have already suffered heart attacks as a result of taking Vioxx and of that number, “30-40% probably died.” (Note that another respected expert, Dr. Eric Topol, estimated the heart attack figure to be up to 160,000).

Dr. Graham put these astounding figures in perspective by using various examples. Most compelling, however, was the following statement:

“Imagine that instead of a serious side effect of a widely prescribed prescription drug, we were talking about jetliners…If there were an average of 150 to 200 people on an aircraft, this range of 88,000 to 138,000 would be the rough equivalent of 500 to 900 aircraft dropping from the sky. This translates to 2-4 aircraft every week, week in and week out, for the past 5 years. If you were confronted by this situation, what would be your reaction, what would you want to know and what would you do about it?”

“Even more revealing, a mere 6 weeks before Merck pulled Vioxx from the market, CDER, OND and ODS management did not believe there was an outstanding safety concern with Vioxx. At the same time, 2-4 jumbo jetliners were dropping from the sky every week and no one else at FDA was concerned.”

“At this meeting [Sept. 22, 2005], the reviewing office director asked why had I even thought to study Vioxx and heart attacks because FDA had made its labeling change and nothing more needed to be done. At this meeting a senior manager from ODS labeled our Vioxx study ‘a scientific rumor.’ Eight days later, Merck pulled Vioxx from the market, and jetliners stopped dropping from the sky.”

The history of the pharmaceutical industry and its interaction with the FDA is replete with well-publicized instances of fabricating and falsifying data, concealing negative information and adverse event reports, ethical violations, conflicts of interest, undue influence, favoritism, and other forms of conduct designed to improperly influence FDA decision making.

When such factors are considered in conjunction with the administrative problems faced by the FDA on an ongoing basis, the mix is quite problematic.

This is most disturbing to critics, however, in situations where a drug, which should never have been marketed in the first place, must be withdrawn from the market. In those cases, the pharmaceutical company involved will invariably seek to avoid liability by setting up the defense that the FDA’s approval of the drug is the best evidence that the drug is safe and effective.

When it comes to approving new drugs, however, is FDA approval the “gold standard” or something dramatically less? An analysis of the FDA’s review process (generally) with particular emphasis on what occurred in the case of Rezulin demonstrates the degree to which FDA approval is open to question.

At a Rezulin Litigation Conference held in Washington D.C. on June 14-15, 2000, Christopher Tisi, Esq. of the law firm of Ashcraft & Gerel submitted a detailed analysis of this very issue. The following is a brief summary of that analysis.

The FDA’s Review Process is Flawed and Resulted in an Inadequate Review of Rezulin

A. The FDA Approval Process Generally is Subject to Abuse

1.      The FDA does not “test” proposed new drugs. It relies almost exclusively on safety and efficacy data provided by the drug’s sponsor.

2.      The FDA is increasingly understaffed. A single Medical Officer is primarily responsible for each NDA. That reviewer may be responsible for many new drugs at the same time.

3.      Since there is no limit to how much information a company can submit to the FDA, a sponsor has ample opportunity to bury or hide data or to present data in a biased or misleading fashion.

4.      FDA resources have been further stretched in the past ten years by increased pressure from Congress and the industry to approve drugs at an accelerated rate.

5.      Although the FDA claims that the removal of over 10 drugs from the market since 1996 indicates that the system “works,” the facts are to the contrary.

B. The FDA Approval of Rezulin Was Subject to Abuse

1.      Rezulin was the first drug to be granted “fast track” status under the Food and Drug Administration Modernization Act of 1997. This meant that the FDA had only 6 months to review the NDA before Rezulin was approved in January, 1997.

2.      The FDA Medical Office initially in charge of reviewing the Rezulin NDA (Dr. John Gueriguian) a twenty year veteran of the FDA, was removed from the project in November, 1996, only weeks before the FDA’s Medical Advisory Board was set to consider whether to recommend approval of the drug. The removal came at the request of Warner Lambert, ostensibly because he had used intemperate language in describing the safety and efficacy profiles of the drug. Significantly, this medical Officer had concluded that Rezulin was no more effective in treating diabetes than other drugs already on the market yet it had potential hepatic (liver) and cardiac (heart) side effects. (This scenario of either removing, discrediting, or ignoring the FDA’s own reviewing officer has become a recurring theme – it happened in the cases of Vioxx and Pargluva as well.)

3.      As a result of inadequate study, Rezulin was marketed in March, 1997 without any warning of liver toxicity while representing its adverse effects were no worse than those seen with placebo.

4.      Almost immediately, the FDA began receiving reports of severe liver failure (as predicted by Dr. Gueriguian). By November, 1997, the FDA had received 35 reports of liver damage, including liver transplants and death.

5.      Although Rezulin was withdrawn from the market in England in December, 1997 and despite the warning of the FDA’s own (new) Medical Officer, Dr. Robert Mishbin, that 12,000 patients may suffer liver damage, the FDA reaffirmed its commitment to Rezulin.

6.      Notwithstanding the extreme dangers posed by Rezulin, the warnings lagged far behind, and required four major revisions between November, 1997 and June, 1999.

7.      Even in the face of overwhelming evidence that the risks posed by Rezulin far outweighed any benefit the drug had, the FDA Advisory Panel did not recommend withdrawal of the drug.

8.      On March 21, 2000 the FDA withdrew Rezulin from the market. By that time, the FDA was aware of 90 liver failures, 63 deaths, and 7 liver transplants.

Based upon the above, Mr. Tisi concluded that the FDA is not “the Gold Standard” for the safety and efficacy of a new drug, particularly Rezulin. In addition to the information in Mr. Tisi’s analysis, the Rezulin debacle presented additional indications that the FDA approval process is highly suspect.

Dr. Anne Peters, an endocrinologist at the University of California at Los Angeles, noted that the serious problems associated with Rezulin had been apparent while the drug was being tested.

In fact, the abnormal test results were so extreme that Dr. Peters stated they should have been regarded as a “red flag.” Many doctors believed that Rezulin should have been marketed from the very beginning with strong warnings and the requirement that those taking the drug have frequent tests of liver function. The drug was marketed with no such warnings. (All of this is eerily similar to what happened in the case of Vioxx.)

In addition, the FDA threatened its own Medical Officer, Dr. Mishbin, with disciplinary action and dismissal from federal service for his January 24, 2000 e-mail to his superiors which stated: “I see no reason why any well-informed physician would continue to prescribe {Rezulin}.”

He also stated that he saw no reason why the “FDA should delay in taking steps to remove [Rezulin]} from the market.” Dr. Mishbin, who had originally supported the approval of Rezulin, was joined by four senior FDA physicians in calling for the withdrawal of Rezulin.

In 1999, the FDA’s own Dr. David Graham warned the agency’s Advisory Committee that every Rezulin user was at risk for sudden liver failure even with monthly monitoring.

Finally, Dr. Gueriguian, who was removed from the review of the Rezulin NDA in November, 1996 after voicing strong reservations about the drug, saw his negative review of Rezulin purged from FDA files. What does that say about the agency’s commitment to safeguarding the public by conducting comprehensive reviews that are beyond reproach?

When the FDA announced it would hold hearings regarding the safety of COX-2 inhibitors, the hope was that the agency would finally shed its image as guardian of the pharmaceutical industry. If ever there was a perfect opportunity for the FDA to reverse years of accusations and innuendoes concerning its questionable record in protecting the public; this was it.

With Merck’s unprecedented massive voluntary withdrawal of Vioxx, the revelation of previously unreported adverse study results, a highly respected (FDA employee) “whistleblower” and other well respected scientists poised to offer damaging testimony, the entire class of COX-2 inhibitors appeared to have “one foot in the grave and the other one on a banana peel.”

When the testimony was in and the votes counted, however, Celebrex, Bextra, and yes, even Vioxx, rose from the ashes, like the Phoenix of myth and legend, to fly again with the renewed approval of the FDA.

An unfavorable finding would have given the injured plaintiffs in the pending and prospective litigation against Merck and Pfizer a significant advantage since they would have been able to point to Merck’s withdrawal of Vioxx and an FDA ban on all COX-2 inhibitors as proof positive that the drugs were, and had always been, too dangerous to be on the market.

The only way the FDA could make it appear as if it was looking out for the public’s wellbeing while still protecting the drug companies from a major financial catastrophe would be to make certain that the vote would not go against any of the drugs no matter what the evidence showed.

Of the thirty-two government drug advisers who would vote on the issue, ten had consulted for Merck or Pfizer in recent years. When the votes were tallied, the results were shocking to many but quite predictable if the FDA’s questionable track record in protecting the public was taken into consideration.

The committee voted unanimously that all of the drugs significantly increased the risk of heart attack and stroke. Despite this finding, which could not have been otherwise, Vioxx, a drug pulled from the market by its own manufacturer (Merck) only four months before, rose from the ashes on the wings of a 17-15 vote. (Without 9 of the 10 “questionable” votes going in favor of the drug, however, the committee would have voted 14-8 to ban Vioxx).

Bextra, a drug with its own serious legal problems, survived by a margin of 17-13-2 (abstentions). (That vote would have been 12-8 against Bextra without 9 favorable votes from the 10 advisers in question).

Celebrex survived by a 31-1 margin (even though the evidence against it was equally compelling). (The vote still would have been an amazing 21-1 in favor of Celebrex without the 10 “interested” voters).

Needless to say, the vote was met with shock and outrage by activists, medical experts, and researchers alike. Several highly reputable news agencies like CBS News, the New York Times, and Forbes, for example, also questioned whether the panel had been “stacked” in favor of the pharmaceutical companies with advisers who had significant “conflicts of interest.”

The FDA and its safety procedures have been criticized variously by investigative reporters, activists, FDA employees, and medical experts as follows:

·        “FDA Drug Oversight Fails Patients” (AP 5/23/01)

·        “FDA Failing in Drug Safety, Official Asserts” (The New York Times, 11/19/04)

·        “Are Too Many Unproven Drugs Receiving FDA Early Approval?” (The Wall Street Journal, 3/1/05)

·        “A Rudderless, Leaderless FDA” (Los Angeles Times, 1/18/05)

·        A broken agency that needs to be “fixed” (Forbes, 1/13/05)

·        “Study Faults Drug Approval Mechanism” (Yahoo! News, 5/7/02)

Notwithstanding the fact that the FDA has been portrayed as a “failure” when it comes to protecting the public, such an analysis is far too simplistic.

In its 68 years of existence, the FDA has always been embroiled in the ongoing conflict between consumer safety and corporate profits. In 1927, Congress created the Food, Drug and Insecticide Administration. It was renamed the Food & Drug Administration (FDA) in 1937.

In 1933, President Roosevelt drafted legislation to strengthen the FDA and protect the public from unsafe, ineffective drugs. However, drug industry lobbyists kept the legislation trapped in committee for 5 years. Eventually, the bill was “gutted” it of its efficacy requirements.

A major disaster and a public outcry to bring about reform came in 1937, when “Elixir of Sulfanilamide,” containing a sulfa “wonder drug” mixed with a solvent closely akin to radiator antifreeze, caused 108 deaths; most of them children.

This prompted new legal requirements that safety be proven before new drugs could be marketed. The comprehensive Food, Drug and Cosmetic Act of 1938 remains the basic law governing the FDA. Drugs marketed before 1938, however, were permitted to remain on the market without proof of safety.

Being able to influence the drug approval process is the industry’s goal and it has limitless funds with which to accomplish that objective.

The reason for this is that the FDA has the potential to: (1) affect billions of dollars in pharmaceutical industry profits; (2) cause significant stock market fluctuations; (3) have an impact on pending and prospective litigation; and (4) make determinations which could actually cause a drug company to go out of business.

Unfortunately, on the other side of this “tug of war” is the noble ideal of protecting the public. Activists, “whistleblowers,” professors, and other crusaders, however, cannot even begin to match the financial and political clout possessed by the pharmaceutical industry.

In fact, the pharmaceutical lobby is the largest in the country. When it comes to buying “access” and influencing politicians, drugmakers are in a league of their own.

Pharmaceutical companies are in business to make money.  The industry is highly competitive, with several companies often racing to be the first to market with a particular type of drug for a specific disease or illness.

Winning the race can mean billions of dollars in profits before other companies even get their drug approved. (This was the case with Viagra which, for years, monopolized the market as a treatment for erectile dysfunction until Levitra and Cialis were approved.)

The fierce nature of the competition has also flooded the market with multiple versions of the same class of drug (COX-2 inhibitors like Vioxx, Celebrex, Bextra, Arcoxia, and Prexige for example) or different treatments for the same condition (statins, resins, fibrates, and niacin for high cholesterol).

The race to get new drugs approved and on the market as quickly as possible has made (pre-marketing) long-term studies a thing of the past.  As a result, the public either turns out to be the test group for long-term use or is exposed to a drug for years before on-going long-term studies disclose its dangerous side effects.

Pharmaceutical companies often claim that it is more important to get a new drug to the people that need it and that massive longitudinal studies would only delay the release of the drug.

The FDA abides by a simple yet essential question in its approval process: Do the benefits of a drug outweigh its risks?  This idea of risk vs. benefit was first adopted about 30 years ago but it is now the basis for new drug approval.

The current law states that all new drugs need proof that they are effective, as well as safe, before they can be approved for marketing. The problem with the current approval process, however, is that even when the answer to this question turns out to be “no,” many dangerous drugs have either been approved or permitted to remain on the market for considerable lengths of time.

For example, Michael Elashoff, an FDA reviewer and biostatistician, was asked to review the flu drug Relenza back in 1995.  Elashoff recommended against approval due to the lack of efficacy of the drug and the agency advisory committee agreed and voted 13 to 4 against approving Relenza.

Yet Relenza was ultimately approved by the FDA and Elashoff was told that he would no longer make presentations to the advisory committee.  Rezulin and Vioxx were both approved and marketed for years despite the fact that strong evidence of their potentially dangerous side effects was well known while the drugs were still being tested.

In the case of Rezulin, the drug was quickly approved by the FDA despite many unanswered questions about safety and efficacy.  Also, despite several indications of liver problems and the withdrawal of Rezulin in Britain, the FDA repeatedly dismissed and ignored warnings of the scientists entrusted with the responsibility of approving new drugs.

This very same failing persists today as witnessed by the Vioxx debacle. Clearly, nothing will change until either a new approval mechanism is put in place or a new agency with greater accountability and resources is formed.

Despite the complex nature of today’s drugs, the FDA is processing new drug applications at a record pace.  From 1993 to 1999 the FDA approved 232 drugs known as “new molecular entities.”

This term is used to describe a new drug which does not already exist in prescription or over-the-counter form.  During the previous seven years, the FDA only approved 163 new molecular entities.

Dr. Solomon Sobel, director of the FDA’s metabolic endocrine drugs division throughout the 1990s, said that there was extreme pressure to meet deadlines and complete reviews.  “The basic message,” he said, “is to approve.”

FDA officials claim they can only do so much to protect the consumer and that physicians must play a greater role in the proper administration and monitoring of drugs.

Many experts see direct-to-consumer (DTC) advertising as a real problem because it targets patients who have no medical or pharmacological training. Doctors complain that patients now demand prescriptions for drugs based upon claims made in DTC advertisements.

It is important to know and accept the fact that all drugs have the potential to cause side effects or allergic reactions. It is also true that the list of side effects that accompany any drug will never be totally complete as there are always cases of people having unpredicted and unprecedented reactions to new drugs as well as drugs which have been on the market for years.

Many dangerous interactions between two or more drugs, between a drug and another substance like food or alcohol, or between a drug and something as common as sunlight are not discovered until after a drug is on the market.

Public Citizen, a respected public watchdog organization (, has drafted a guideline for consumers called the Seven-Year Rule which states that you should wait at least seven years from the date of release to take any new drug unless it is one of those rare “breakthrough” drugs that offers you a documented therapeutic advantage over older proven drugs.

This “rule” is based on three major factors: inadequate testing, the probability that a dangerous drug will be withdrawn within seven years, and the addition of adverse reaction warnings to new drugs within their first seven years on the market.

In April of 2002, the Journal of the American Medical Association (JAMA) published a study led by Dr. Karen Lasser of Cambridge Hospital and Harvard Medical School which concluded that one in five new drugs has unrecognized adverse drug reactions (ADRs) that do not show up until after the drug has been approved.

The study analyzed 548 drugs approved from 1975 through 1999 and discovered that 56 of them were later given a serious side-effect warning or even taken off the market completely.

Dr. Sidney Wolfe of Public Citizen, who worked on the study, said: “Most troublesome drugs do not represent any advance in treatment and are at best no better than older, safer drugs already on the market.”

The study specifically focused on black box warnings, which highlight the most serious side effects that were added to the drug’s label after its release.  If one of the more life-threatening side effects is not detected prior to release, it can cause major problems and create a serious hazard for the general public once the drug is on the market.

In addition, if a serious ADR is discovered, all drugs in that class should be reviewed as they may pose the same previously undetected risks. This is certainly the case with the entire class of COX-2 inhibitors.

Unfortunately, once a prescription drug is approved for marketing, it is extremely difficult to have it withdrawn. Public Citizen has petitioned to have many dangerous drugs banned including the COX-2 inhibitors, Meridia, Crestor, and Accutane. World-renowned experts have offered clinical studies and scientific proof that numerous drugs are far too dangerous to be on the market or should not be prescribed to certain groups of patients, especially children and adolescents. Highly experienced FDA drug reviewers have advised against approving many drugs that were later withdrawn from the market.

Even though every one of these challenges was well-founded and meticulously documented, none has ever been relied upon as a basis for withdrawing an approved drug from the market. Public Citizen’s petitions have not been successful, the experts have been ignored, and (probably worst of all) the FDA reviewers have been ignored, humiliated, transferred, and otherwise discredited by their own agency.

When the FDA finally believes a drug is no longer safe to use, it will ask the manufacturer to withdraw the drug voluntarily. Usually, the company agrees and the drug is immediately pulled. Sometimes, as in the case of Vioxx, a drug is voluntarily withdrawn when the manufacturer determines it can no longer be safely marketed or when the <"">personal injury claims against manufacturer make it award big sums to numerous sufferers.

Today, most withdrawals can be traced directly to either inadequate pre-application testing, inadequate disclosure in the application process, or inadequate FDA scrutiny of existing data and expert opinions.

Although known side effects cause more injuries and deaths than unknown side effects, it can be quite unnerving for a patient to experience a reaction he or she was not warned about.  Sometimes, an unknown side effect can be even more serious than the existing ones.

Limited studies (both in duration and in group size) are more likely to “miss” a particular side effect or potential risk than studies conducted on large test groups over an extended period of time.

Robert Temple, M.D., director of the FDA’s office of medical policy claims that test groups cannot be made larger and research studies cannot be dragged out since the public requires “reasonably rapid” access to needed drugs.

Unfortunately, once a drug is placed on the market, millions of people will be exposed to it for extended periods of time.  Thus, short-term studies involving limited test groups offer little assurance that all serious side effects, allergies, dangerous interactions, and long-term problems have been discovered prior to marketing.

It is for this very reason that Public Citizen’s “seven-year rule” makes sense. Regrettably, during that seven year period, the public itself is acting as the test group.

The editors of the Journal of the American Medical Association (JAMA) recently made an extremely valid point about the position of the FDA.  They argued that it was “unreasonable to expect that the same agency that approves drugs to also be committed to actively seek evidence to prove itself wrong.”  They suggested the creation of an independent drug safety board to monitor the safety of drugs and medical devices following FDA approval, as it is no longer the “gold standard” it once was.

There are currently six drugs on the market that have the potential of becoming the next Vioxx if a new system is not instituted rapidly and efficiently. These drugs are now all under serious scrutiny because of the serious risks they pose.

  • Accutane (acne medication linked to suicides and birth defects)
  • Crestor (cholesterol-lowering drug known to cause kidney failure)
  • Meridia (weight-loss pill that can cause substantial increase in blood pressure)
  • Cymbalta (which already carries a Black Box Warning regarding “Suicidality in Children and Adolescents,”) is now linked to post-marketing reports of hepatic injury (including hepatitis and cholestatic jaundice) that suggest “patients with preexisting liver disease who take duloxetine may have an increased risk for further liver damage.”
  • Strattera – On September 28, Eli Lilly declared that it was adding a black-box warning to its attention deficit (AD) medication. The new warning will claim that the drug may increase suicidal thoughts among youths.
  • Serevent (asthma medication linked to an increased risk of asthma related deaths)

While these drugs all represent cases where the risks outweigh the benefits and, thus, fail to comply with one of the key standards for approval by the FDA, they remain on the market with the FDA simply requiring stronger warnings or more careful monitoring of patients.

This reinforces the notion that the FDA can no longer be trusted to police either itself or the multi-billion dollar pharmaceutical industry it was created to regulate and supervise.

Thus, the GAO report comes with volumes of evidence upon which to have based its conclusions. It would have been quite astonishing had the GAO findings been anything but what they were.

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