Posted today by the PostScript blog at Community Catalyst:

Posted on: August 4, 2010; 11:53 am

Yesterday, Senator Michael Bennet (D-CO) unveiled new legislation that seeks to improve the safety of America’s drug supply. The Drug Safety and Accountability Act of 2010 is an important first step in solving a growing problem. It mandates improvement of industry safety and quality standards for both prescription and over-the-counter drugs, provides increased FDA oversight, and gives the FDA much-needed authority to actively protect the drug supply through mandatory recall of dangerous products, as well as to subpoena documents and witnesses. The bill also improves enforcement through whistleblower protections and civil monetary penalties for industry violations.

In announcing the filing of the bill, Sen. Bennet shared his concerns about the issue and his commitment to ensuring the American drug supply is safe no matter where its drugs are made. “Making sure pharmaceutical drugs meet the highest standards for safety and quality is important to me, not only as a U.S. Senator, but as the father of three little girls as well,” said Sen. Bennet in a press conference organized by the Pew Prescription Project. “For too long, the FDA has lacked the proper authority to adequately safeguard our drug supply and protect Colorado consumers.”

Why now?

Americans are concerned about the drug supply, says a Pew Prescription Project survey released yesterday, and they have reason to be.

Manufacturing of pharmaceuticals has changed dramatically in recent years, with more than 80 percent of the active ingredients in all U.S. prescription drugs now originating overseas, often in countries with weak regulatory and enforcement infrastructures such as China and India. In these counties, where quality standards differ from our own and where responsibility for drug purity is murky at best, it is increasingly difficult for the FDA to ensure the safety and efficacy of a drug when they cannot track the uncertain and complex manufacturing processes.

According to the Pew Prescription Project survey, the confidence Americans have in drugs made in some countries overseas is next to none. While three out of four Americans believe drugs made in the U.S. are contaminate-free, only one in 10 believes the same for drugs made in China or India. What’s more, most believe Congress should do more to legislate in this area and over half of those surveyed favor FDA inspection of overseas drug companies.

The recent recalls of Johnson & Johnson’s children’s Tylenol and other cough & cold medicines were another wake-up call to protect Americans from the risks of unsafe drugs, but they were also the most recent in a long line of issues.

The numbers are telling

• In June, drug manufacturers recalled intravenous bags of certain antibiotics manufactured in India found to be unsterile and at least in one case to contain mold.
• In May, the FDA sent a warning letter to a pharmaceutical company for failing to set quality standards for its outsourcing that allowed them to skirt important safety practices.
• There were more than 1,700 drug recalls in 2009 – four times more than in 2008. Most of the recalls were for problems related to manufacturing quality and testing.
• In 2007 and 2008 a contaminated blood thinner, heparin, made in China entered this country and more than 100 Americans died in that case.

Community Catalyst is collaborating with the Pew Prescription Project to spearhead work on this issue in the best interest of American consumers.  The impact of drug safety problems is potentially enormous, given that adults and children alike have increasingly come to rely on pharmaceuticals for the cure and management of a wide variety of common, chronic and serious medical conditions. Indeed, Kaiser reports that the use of prescription medications has risen 39 percent in the last decade in the U.S. while the population grew 9 percent. Today 90 percent of seniors and 58 percent of other adults rely on a prescription medication on a regular basis. Among children, a 2009 survey found that 56 percent had used at least one medication in the previous week, and most of those were over-the-counter products (Pediatrics, August 2009).

With the goal of addressing this problem by strengthening the regulation of the manufacturing process for drugs, Community Catalyst supports Sen. Bennet’s legislation and is working to educate and assemble national and state groups to do the same.

– Jessica Hamilton, Program Associate

You may view the latest post at: http://postscript.communitycatalyst.org/?p=1549

Billion-dollar settlement of Paxil birth-defect lawsuits

Only a week after Glaxo SmithKline (GSK) agreed to pay $460 million to settle over 10,000 personal injury lawsuits related to Avandia,  it was reported that GSK has agreed to pay $1 billion dollars to settle  800 cases related to birth defects caused by  the GSK anti-depressant Paxil, taken by pregnant women. Both of these settlements are part of the $2.4 billion GSK has set aside to resolve pending litigation, according to corporate filings last week.

This $1 billion Paxil settlement will provide an average payout of more than $1.2 million to each family of an affected child, many of whom are left with heart defects as a result of their mother taking the drug. However, this settlement leaves more than 100 related cases still pending.

This settlement also follows a recent trial in Philadelphia, where a jury awarded a family $2.5 million for their child’s heart birth defect caused by Paxil. That lawsuit revealed internal “Glaxo documents showing executives talked about burying negative studies about Paxil’s links to birth defects and that its own scientists were alarmed by the rising number of children who had been affected by the drug in the womb.”

These recent settlements, combined with  earlier ones related to allegations that Paxil caused suicide, attempted suicide, and addiction, brings GSK’s total settlements on Paxil to over $2 billion so far.

Yet GSK sales of Paxil, one of the true blockbuster drugs in the last 15 years, generated $11.7 billion in US sales between 1997 and 2006. So GSK has profited dramatically from this drug, while leaving a wide trail of shattered lives and grieving families.

Despite these settlements and the 2005 black-box warning the FDA added to the drug’s label on increased risks of suicidal thoughts among adolescents, Paxil still earned $793 in sales in 2009.  It continues to be one of the more profitable drugs on the market.

Avandia study suspended, conflicts revealed

In a statement released yesterday, the FDA placed the TIDE (Thiazolidinedione Intervention with Vitamin D Evaluation) study comparing Avandia with its rival Actos on a “partial clinical hold.” This means that no new subjects can be enrolled, but that existing subjects can continue to participate.

This decision by the FDA is not all that surprising since, even though the FDA’s Advisory Panel voted 19-11 last week to recommend that the study continue, there was at least one member of the panel who questioned whether it was ethical to continue this study in light of the known serious cardiac risks.

Though the FDA had previously stated that they issued no conflict of interest waivers for the advisory panel hearing last week, two conflicts have since come to light. David Capuzzi, an endocrinologist on the panel, earned $3,750 last year (and $14,750 in total) as a speaker for another GSK drug, Lovaza. Though Dr. Cappuzzi denies he ever spoke about Avandia, a GSK spokesman reported that at least one of Capuzzi’s talks prior to 2008 was on Avandia. It is noteworthy that Dr. Capuzzi defended Avandia during the advisory panel hearing and voted to keep it on the market despite the fact that he claimed he rarely prescribes Avandia as he does not “like the whole class of drugs” and prefers to prescribe metformin.

Dr. Capuzzi explained his failure to disclose by saying that “the FDA doesn’t consider a different product for the same company to be a conflict of interest.” He furthermore said that he did not disclose this information to the FDA because he was never asked about it.

…. Really?

Pharmalot (hat-tip) reports that the FDA policy requires that panel members “report all current financial interests and those held within the previous 12 months that could be affected by the discussion and outcomes of the meeting, or that would present appearance issues.”

The FDA went on to say that they “take these allegations [against Cappuzzi] very seriously and [are] investigating the matter.” Additionally, Pharmalot reported that an FDA spokeswoman stated that “a decision [on their investigation] is expected by the end of the week and, if the agency determines there was misconduct, the matter could be referred to the HHS Office of Inspector General.”

On the flip side, the Wall Street Journal reported yesterday that Abraham Thomas, a doctor who voted to take Avandia off the market, was a paid spokesman for Takeda, who produces Avandia’s rival drug, Actos. Dr. Thomas was a member of the Takeda Diabetes Speakers Bureau from September 2007 to September 2008 and received $5,000 for giving two presentations. It is currently unclear if Dr. Thomas will be investigated by the FDA as well, since his relationship with Takeda took place over a year ago.

Ultimately, other panel members that have been interviewed do not feel that these conflicts of interests affected their decisions. One stated, “the panelists came prepared and had very strong opinions [that] won’t be easily swayed by other people’s opinions unless they’re very compelling,” but one panelist did say that the FDA “encourage[d] us to err on overdisclosing  [and]  to disclose anything in [our] past that may have relevance.” You would think that a paid relationship with the pharmaceutical company in question, or one with the drug’s  major rival in its class would be relevant enough a potential conflict for someone to disclose.

Panel decision-making warrant scrutiny 

 Finally,  in even more news to cause the public to question the reasoning methods used by the Avandia advisory panel, it was recently reported by the USA Today that at least one of the 10 advisory panel members who voted to keep Avandia on the market with tight restrictions says he’d actually prefer that the FDA withdraw it. This panelist, Clifford Rosen, has publicly stated that the only reason he didn’t vote to withdraw Avandia from the market is because he was “very anxious” he’d be the only one to vote that way. Dr. Rosen, who chaired the 2007 advisory committee meeting where panelists voted 22-1 to keep Avandia on the market despite the cardiovascular risks associated with the drug, says that he and the 21 other panelists who voted to keep the drug on the market  did so because they did not know whether Actos may be even riskier. Despite his previous vote, Rosen has stated that he has not prescribed Avandia since this 2007 meeting.

 After all this, we clearly haven’t heard the last on Avandia ….

Following up on last week’s blog discussing the FDA hearing underway to determine the safety of the prescription diabetes drug, Avandia, the FDA advisory review panel concluded a two-day hearing last Wednesday by recommending 20 to 12 that Avandia remain on the market with label revisions and other restrictions. This deeply divided panel included 17 votes to add warnings or restrictions on the drug, and 12 votes to remove the drug from the market.

The members voting for Avandia’s removal said the drug “has no unique benefits and therefore the benefits of the drug do not outweigh the risks.” They also pointed out that Avandia’s primary competitor, Actos, is an acceptable alternative to Avandia and therefore there is no therapeutic necessity to keep Avandia on the market.

Even the use of Actos has been called into question. Harvard researchers based at the Independent Drug Information Service (www.RxFacts.org), note that “in mid-2007 the FDA added black-box warnings cautioning that both rosiglitazone (Avandia) and pioglitazone (Actos) increase the risk of congestive heart failure.” These safety concerns, “along with an increased risk of fracture, have greatly dampened enthusiasm for use of both of these drugs.”

The ultimate fate of Avandia now rests in the hands of the FDA who stated that they “took the panel’s advice seriously and that [the FDA] would consider its regulatory options.” If the proposed additional warnings and restrictions are implemented, scientist Steve Nissen, who published the first study documenting the cardiac risks of Avandia in 2007, estimates that 95 percent of Avandia’s use will end. “Effectively, this drug is gone.”

Interestingly, the committee also recommended by a vote of 19-11 that the trial currently underway comparing Avandia to its rival Actos be continued, though at least one member questioned the ethics of this, given the potential risks.

Litigation yields access to studies, helps expose risks

Litigation plays a valuable role in exposing industry schemes to withhold safety data. For instance, GSK’s earlier suppression of studies showing risks associated with the drug Paxil lead to litigation and settlements that required GSK to post information on-line about all their clinical trials. It was this posted information that Nissen and fellow researcher Kathy Wolski of the Cleveland Clinic used to perform their 2007 analysis of over 40 studies that showed that Avandia raised the risk of heart attack, stroke and death in comparison to Actos.

Another example of the benefit of litigation is seen by the PAL-member class action lawsuit concerning the drug Zyprexa whichyielded hundreds of documents, some of which revealed Eli Lilly’s own internal studies documenting the increased risks that Zyprexa posed as a treatment for dementia in elderly patients.

New evidence, studies bring risks to light

Ongoing investigations by Senator Grassley and almost a dozen new studies documenting the risks of Avandia have kept the issue alive, prompting the FDA’s ongoing review, including last week’s hearing.

One comparative effectiveness study by David Graham of the FDA was published this past June. Graham worked with researchers at the Centers for Medicare and Medicaid Services to collect records from nearly a quarter million Medicare recipients.  Elderly diabetics, who used Avandia instead of its competitor, Actos, had a 68 percent increase in the risk of heart attack, stroke, heart failure or death. Graham stated:

“We estimate that about 48,000 excess cases of [heart attack], stroke, heart failure, or death were attributable to the use of [Avandia] rather than [Actos] from 1999-2009.”

Graham additionally stated “the RECORD study would have been dismissed as ’garbage’ if it had been used to seek the drug’s original approval.”

What’s next?

The question of whether the FDA will allow Avandia to remain on the market is still up in the air.  Beyond that, what else can we do to stop such illegal and hazardous industry behavior—the same behavior that resulted in the Vioxx tragedy, which lead to up to 60,000 deaths? As litigation and other sources have revealed suppression of drug risks concerning Vioxx, Paxil, Celexa, Zyprexa, and many other drugs, the problem seems endemic.

To begin to address this problem, the FDA needs the resources and authority to examine all relevant clinical studies for data-tampering. Government and private consumer lawsuits must continue, including possible criminal prosecution. Finally, we should all remember that what you read on your drug label or hear in a TV ad may not be the whole story. Skepticism is warranted and further regulation is critical to all of us–we need medical care we can trust.

Monday’s story by New York Times reporter Gardiner Harris revealed that Glaxo SmithKline (GSK) had withheld studies showing serious risks associated with the world’s former best selling diabetes drug for 11 years.

GSK withheld results from a 1999 study that they conducted comparing Avandia to its main competitor, Actos. Rather than demonstrate that Avandia was safer, this 1999 study linked Avandia to a 43 percent increased risk of heart attacks. GSK never reported these findings to the FDA, and has spent the last 11 years trying to cover them up.  One GSK executive at that time even said in email exchanges that:

 “Per Sr. Mgmt request, these data should not see the light of day to anyone outside of GSK.”

In fact when one GSK official asked about whether two of the drug trials in question should be published, this same executive responded:

“Not a chance. These put Avandia in quite a negative light ….”

But the case against GSK doesn’t stop there. In addition to failing to disclose these results to FDA,  there is evidence that GSK researchers excluded a dozen serious heart problems in the total tally of adverse events from their 6-year ‘RECORD’ study on Avandia released in 2007.

One FDA reviewer  found a number of instances where “deaths that occurred while taking Avandia were inexplicably dropped from the final analysis.”

A former manager of the FDA’s drug safety unit, Rosemary Johann-Liang, revealed in a deposition last month that Glaxo withheld from FDA other records from 2001 showing Avandia may cause heart attacks and that Glaxo did not turn over an e- mail from researchers who concluded Avandia “strengthens the signals” of heart ailments.

Does this leaves anyone else with a feeling of déjà vu? This is Vioxx all over again. In 1999, manufacturer Merck withheld studies or other data documenting  the serious cardiovascular side effects associated with Vioxx. This block-buster drug rose to $2.5 billion in annual sales before its risks were revealed in 2004. Some estimate Vioxx led to 44,000 deaths and 80,000 heart attacks.  While this Vioxx scandal resulted in a record-breaking $4.8 billion dollar settlement of 26,000 personal injury claims, many feel that Merck got away with murder, or at least manslaughter. And while $4.8 billion is a lot of money even to Merck, their gross sales of Vioxx were far greater.

Another example of  drug industry executives putting profits ahead of patient safety.

What’s next for Avandia? And GSK?

Today’s panel at FDA will decide whether to recommend that the drug be withdrawn from the market.

GSK has negotiated over 10,000 settlements for $460 million, according to Business Week. This seems like a small amount. Certainly other cases are bound to follow.

A week or so ago we blogged about comments Prescription Access Litigation and others made to the FDA in support of proposed rules on presenting risk information in broadcast drug ads.

Numerous other consumer and public health groups have commented, and overall offered resounding support for these proposed regs. The Patient, Consumer and Public Health Coalition offered their support for these regulations and stressed that “the goal of DTC ads is to persuade, not to educate, and so DTC ads emphasize the benefits but not the risks of prescription drugs.”

Consumer groups, including the National Consumers League, additionally offered support for the proposed fifth requirement of dual-modality, simultaneous audio and textual presentation. Consumers Union voiced the importance of dual-modality in their comment stating that “[p]roviding an audio warning with other things happening in the background is, no matter how hard one tries, distracting” and, “[p]roviding a text warning while talking about other things is distracting;” “Providing the same, simultaneous audio and visual warning is the single best way to make a lasting impression that will be helpful to patient-consumers.”

Some consumer groups also argued that pre-review of ads should be required. Here’s Public Citizen: “to obtain approval of DTC advertising on broadcast media, a party shall present market research demonstrating that information concerning side effects, contraindications and warnings is comprehensible to the target audience.” A pharmacists group and pharmaceutical powerhouse Eli Lilly also supported the use of focus groups to review and “pre-approve” ads and to pilot test that elements (e.g. font size, color, placement) of an ad.

In addition to these shared themes, AARP also suggested that the FDA rule should specify where in the ad the “major statement” should appear” and that the major statement should not be allowed to be placed in the middle of the ad “where it can be bookended by conveyance of benefit information and is least likely to be retained by consumers.”

The two pharmacist organizations that commented–the American Society of Health-System Pharmacists and the Academy of Managed Care Pharmacy (AMCP)—supported the new proposed rules, as well as dual modality in ads and pre-dissemination review whether by the FDA or by consumer test groups.

Industry against dual modality, for delays
Industry was relatively quiet on these new proposed regulations:  only the Pharmaceutical Research and Manufacturers of America (PhRMA) and four pharmaceutical companies submitted comments so far. Though industry all stressed the public health benefits of DTCA and generally offer their support for the FDA’s action to further clarify the standards, a few common themes of opposition are apparent in all industry comments.

On the whole, industry seems very opposed to the proposed fifth standard of requiring dual modality. Sepracor argues that dual modality “could prove to complicate the presentation for consumers.” PhRMA seconded this argument and said that “dual modality might produce presentations that actually overemphasize risk information.”

Merck further stated that dual modality “does not improve consumer recall or understanding of important risks information.” Though Merck supported this argument with one 2005 study, it went on to mention the limitations of this study and none of the other industry commenters provided any support for their arguments against dual modality, and all of industry’s comments against dual modality ignore the numerous studies that have shown that the technique enhances clarity and recall of information (and which the FDA cited in its proposed rule).

The second overarching theme of the industry comments seems to be an attempt to delay the implementation of these rules. Sepracor, Merck and Eli Lilly all suggest that the FDA do further research and analysis on these standards before implementation. Sepracor argued that the rule should not be made effective until the results of FDA’s study on the impact of distraction can be published and commented on.

This argument reads largely as a delay tactic employed by Sepracor to postpone the inevitable implementation of this rule. Though there is no doubt that the FDA’s study may help them to further understand what elements of broadcast media can be distracting, there’s little debate that the impact of distraction on consumer understanding… is to distract, and that’s hardly a reason for FDA to delay implementing these rules when the public’s health is at stake.

In one of the more head-scratching unsupported assertions, Sepracor stated that up to 70 percent of the time slot of an ad is used to convey safety information for the drug. Anyone who’s ever viewed one of the numerous DTC ads currently on TV knows that this statistic has little foundation in reality.

–Emily Cutrell, Prescription Access Litigation

(The following blog was posted yesterday on Community Catalyst’s Postscript blog. It highlights an exchange between FDA Deputy Commissioner Joshua Sharfstein an Congressman Dingell concerning the need for increased FDA authority and resources to effectively regulate drug safety.)

Drug Safety: A Duet

March 11th, 2010

Yesterday, the House Energy and Commerce Subcommittee on Health heard from FDA Deputy Commissioner Joshua Sharfstein on the safety of the drug supply and current agency practices to ensure the safety of marketed drugs.

Sharfstein, who has been a strong advocate for drug safety, both at the agency and previously  as health commissioner in Baltimore, made a forceful case for what FDA needs to keep drugs safe: “FDA needs additional tools to move our oversight capabilities into the 21st century.  FDA needs to access regulatory information quickly, hold all parties responsible for the quality of products in the supply chain, and have reasonable and reliable options for enforcement,” he said.

The hearing was notable for the bipartisan consensus that securing the safety of the drug supply is a national priority with high stakes, and unanimous agreement that the FDA’s ability to ensure that safety must be shored up. It convincingly framed drug safety as an equally urgent next step to a food safety measure that passed the House by a wide margin last year.

But perhaps the hearing’s most compelling arguments for a safer drug supply came in this stage-worthy exchange between Sharfstein (JS) and Chairman Emeritus John Dingell (JD), who has worked to support the agency’s drug safety efforts for much of his recent career.

JD: Dr. Sharfstein, I want you to understand these are friendly questions. I want yes or no answers. You are familiar with the heparin crisis, which caused 81 American deaths. Does FDA currently have the adequate resources, personnel, and authorities to prevent another heparin crisis?

JS: No.

JD: Do you have the ability to control the safety of imported pharmaceuticals?

JS: Not to the extent we’d like.

JD: Do you have the authority and resources to address the safety of components being now imported into this country?

JS: No, not to the extent we’d like.

JD: Do you have authorities and resources to see to it that good manufacturing practices (GMPs) are properly observed overseas?

JS: Not to the extent we’d like.

JD: Would you please submit to the committee the number of people that you have at the different ports to ensure the safety and the inspection of pharmaceuticals coming into this country, and also would you give the number you need to see that this is done. Please submit that for the record.

[JS assents]

JD: Do you have adequate authority to keep out unsafe drug shipments at the border?

JS: No.

JD: Do you have authority to require manufacturers to ensure the safety of their supply chain?

JS: No.

JD: Do you have the authority to see to it that GMP are observed in this country on both food and drugs, and abroad? Yes or no?

JS: No, not to the extent we’d like.

…
JD : Do you have adequate authority to require mandatory drug recalls?

JS: No.

JD: Do you need that authority?

JS: We would like it that authority, yes.

JD: Would you like it or do you need it?

JS: I’d say we need it.

JD: [refers to the Food and Drug Administration Globalization Act of 2009 and its cosponsors] [FDAGA] would give you significant authorities to address your current lack of capabilities?

JS: That legislation has very important elements, yes.

JD: It would also give you the [financial resources] you need by enabling you to collect fees from both manufacturers of food and pharmaceuticals? Is that right?

JS: It does have that provision, yes.

JD: And you can do that both at home and abroad, is that right?

JS: I believe so, yes.

JD: Are those resources and fees included in your budget submissions to the Congress?

…

JS: For food it is.

JD: How about pharmaceuticals?

JS: I don’t believe so, no.

JD: Now it’s a curious situation I’ve observed, that you are in the awkward place at FDA of having somebody be able to bring unsafe foods into the United States, and you can’t catch them at the point of entry. But you also have the problem that if you do catch them, you don’t have authority to seize, impound or to destroy. Is that right?

JS: Yes.

JD: So you send them back out?

JS: I believe so. Often that’s what happens.

JD: And they then often bring them back in, through another point of entry?

JS: I think they can try, yes.

JD: Do you have that same problem with pharmaceuticals?

JS: Yes.

JD: So that problem exists in both places. So you have problems with unsafe commodities being brought in—foods and pharmaceuticals. You also have some that are over-aged, improperly stored, contaminated, filthy, improperly packaged. Counterfeit. And you also have some that are full of inert substances, you mentioned talcum powder…Do you have authority to deal with those?

JS: We have some authorities. But not–

JD [interrupts] Do you have enough?

JS: We don’t have enough.

JD: As proven by heparin.

JS: Yes, in part.

JD: And you have coming into this country from China on a fairly regular basis—and from Mexico and other places—unsafe food and pharmaceuticals. I can recall mushrooms. I can recall berries. I can recall tomatoes and jalapeno peppers. I can recall the heparin scare. And a large number of others. This is an ongoing and continuous problem, is it not?

JS: Absolutely.

JD: And you lack the Congressional support, both in authority and money, to do the job that you need to do to protect the American people? Isn’t that right?

JS: Well, we very much want to do more.

JD: I don’t want you to be afraid to say that we haven’t given you  the authority you need—

JS:  No we want more authority—

JD: —If it’s the truth, because we’re going to try to get it for you.

–Kate Petersen, PostScript blogger

 Today, the Supreme Court rejected arguments by the prescription drug industry that having their labels approved by the Food and Drug Administration should be a shield from state law tort liability.  In a rousing victory for consumers of prescription drugs, the Supreme Court rendered a decision preserving consumer rights to access the courts when injured physically or financially by prescription drugs. 

In the case Wyeth v. Levine, the Court ruled 6 to 3 that the FDA’s approval of a drug label does not preempt consumer’s rights to sue the manufacturer for their failure to warn of knows risks associated with the drug. 

The lawsuit was brought by Diane Levine, a musician from Vermont who while suffering from a migraine was given the anti-nausea drug Phenergan. Her physician’s assistant did so in a manner that caused the drug to contact her arteries, which caused gangrene and resulted in the loss of her arm. Ms. Levine sued and settled with her doctor. She also sued the drug’s Manufacturer, Wyeth. In its defense, Wyeth argued that the FDA’s approval of the label under federal law preempted Ms. Levine’s rights under state law, but lost. After a 5-day trial, a Vermont jury concluded that the drug maker did not adequately warn of the known risks of gangrene associated with the use of the drug, and awarded Ms. Levine $7.4 million.

After losing in appeals all the way up to Vermont’s Supreme Court, Phenergran’s manufacturer, Wyeth appealed to the U.S. Supreme Court. The Court accepted the case, and addressed the issue 

whether federal law preempts Levine’s claim that Phenergan’s label did not contain an adequate warning about using the IV-push method of administration. 

In today’s decision, the Court decided that there was no preemption, and found in favor of Ms. Levine.

The Court first noted that it was not impossible for the drug maker to comply with both state law and federal requirements in preparing the drug’s label.  The court concluded that the drug maker could have added warnings to the label at any time to reflect the risks of gangrene that had occurred to over twenty people since the labeling was approved by FDA. Wyeth had incorrectly argued that the federal regulations prohibited their changes to the label, because they must have been based on “newly acquired information….”  The Court countered that Wyeth was incorrect, and that they could have added warnings to reflect the 19 amputations that had arisen from Phenergan’s use before Ms. Levine’s case.

The Court also concluded that Wyeth suffered from a “more fundamental misunderstanding” about the duty to warn consumers of the risks of prescription drugs.  The Court noted that

Wyeth suggests that the FDA, rather than the manufacturer, bears primary responsibility for drug labeling. Yet through many amendments to the FDCA and to FDA regulations, it has remained a central premise of federal drug regulation that the manufacturer bears responsibility for the content of its label at all times. It is charged both with crafting an adequate label and with ensuring that its warnings remain adequate as long as the drug is on the market.

 

Wyth also argued that the Ms. Levine’s lawsuit should be preempted because it interferes with “Congress’s purpose to entrust an expert agency to make drug labeling decisions that strike a balance between competing objectives.” The Court rejected this argument as being both out of line with the intent of Congress, and as based on “an overbroad view of agency’s power to pre-empt state law.”

On the first point, the Court notes that “[i]f Congress thought state-law suits posed an obstacle to its objectives, it surely would have enacted an express preemption provision at some point during the FDCA’s 70-year history” like it did with a 1976 amendment allowing “express pre-emption … for medical devices….”

The Court also spoke to the FDA’s role in the preemption debate, especially it’s position in favor preemption announced in the preamble to the 2006 regulations that redesigned the format and content requirements for prescription drugs.  The Court also assessed how much weight to give an agency position that “state law is an obstacle to achieving its statutory objectives….” The Court found that in cases lacking express authority by Congress, the deference given to an agency “depends on its thoroughness, consistency, and persuasiveness.”  Based on this, the Court decided that FDA’s position “does not merit deference.”   

First, the Court pointed out a glaring procedural lapse by FDA in adopting the position that their regulations and approval of drug label preempts state law.   In proposing the draft rule in 2000, the FDA had stated that the rule would “not contain policies that have federalism implications or that preempt State law.”

Despite this, FDA adopted a position in favor of preemption upon publishing the final rule in 2006. FDA did so “without offering States or other interested parties notice or opportunity for comment….” As a consequence, the Supreme concluded that “[t]he agency’s views on state law are inherently suspect in light of this procedural failure.”

The Court also noted that the FDA position on preemption “is at odds with … Congress’s purposes, and it reverses the FDA’s own longstanding position….” The Court summarized the history of FDA’s relationship to state law, noting that

the FDA traditionally regarded state law as a complementary form of drug regulation. The FDA has limited resources to monitor the 11,000 drugs on the market,and manufacturers have superior access to information about their drugs, especially in the postmarketing phase as new risks emerge.

The Court also stated that

State tort suits uncover unknown drug hazards and provide incentives for drug manufacturers to disclose safety risks promptly. They also serve a distinct compensatory function that may motivate injured persons to come forward with information. Failure-to-warn actions, in particular, lend force to the FDCA’s premise that manufacturers, not the FDA, bear primary responsibility for their drug labeling at all times. Thus, the FDA long maintained that state law offers an additional, and important, layer of consumer protection that complements FDA regulation.12 The agency’s 2006 preamble represents a dramatic change in position.

We recognize this decision as an important victory for consumers, and we applaud the Court for this decision.

We hope to post more details on this decision, and its potential impact on our other lawsuits, soon.

You can read the full decision at

http://www.supremecourtus.gov/opinions/08pdf/06-1249.pdf

This past Wednesday, the Prescription Project, a sister project to PAL at our parent organization, Community Catalyst, filed four petitions with the FDA raising concerns about online advertising of medical devices and drugs on YouTube.com. The petitions cited ads posted on YouTube by Abbott Laboratories (NYSE: ABT), Medtronic (NYSE: MDT) and Stryker (NYSE: SYK).

Within hours, the two videos about Medtronic and Stryker’s devices cited by the Prescription Project were removed, and the remaining videos about an Abbott Laboratoriess device were labeled with safety information, and removed from public access the next day.

The Prescription Project’s petitions have gotten widespread media attention, including articles in the Wall Street Journal, Associated Press, Crain’s Chicago Business, Chicago Tribune, Minneapolis Star Tribune, and Pioneer Press.

The Prescription Project’s press release on the petition is here.

Here is the entry from PostScript, the Prescription Project’s blog, about the request for FDA action:

Devicemakers’ bypass marketing rules on YouTube
December 3rd, 2008

Today the Prescription Project filed a series of citizen petitions with the FDA asking that six YouTube videos be removed immediately from the self-broadcast internet supersite because they appear to have been posted by medical device manufacturers, but do not contain the federally-mandated warnings or provisions required of medical device advertisements.

The videos include four posted by Abbott Laboratories about its XIENCE-V drug eluting stent, one for Medtronic’s Prestige® Cervical Disc, and one for Stryker’s Cormet™ Hip Resurfacing Technology. Here they are.

The Prescription Project is petitioning the FDA, which is charged with regulating the marketing of approved medical devices as well as prescription drugs, to require the makers to remove the ads from YouTube immediately and to post “curative” ads that contain the proper risk information. In addition, the Project calls on the FDA to:

• Advise all major prescription drug manufacturers and medical device manufacturers that online/Internet drug and device advertisements and promotions are subject to the same requirements as drug and device promotions in other media, and recommend that they review their online advertisements for compliance.

• Issue a Guidance on Consumer-Directed Broadcast Advertising of Prescription Drugs and Restricted Devices on the Internet to clarify how federal law and FDA regulations apply to online drug and device promotions.

But who watches YouTube for info about health, anyway? Well, it seems that number is growing rapidly. According to a 2007 survey conducted by the Pew Internet and American Life Project, somewhere between 75% and 80% of internet users have looked online for health information. And a Manhattan Research poll about physician online habits released just last month found that 83% of physicians watch video clips online, as compared with 34% of all US adults.

So statistically, these ads are being seen by both patients and doctors. And without the proper risk information that’s required in other broadcast drug device advertising, that’s a problem.
In fact, we think it’s an even bigger problem because consumers injured by medical devices can no longer sue device manufacturers for failing to warn them about known but undisclosed risks, a result of the February 2008 Supreme Court decision in Riegel v. Medtronic. And consumers injured by prescription drugs may well lose that same right if the Supreme Court issues a similar ruling in Wyeth v. Levine, a case argued before the Court last month.

To read the petitions and view the videos, go here.

Prescription Access Litigation coalition member National Women’s Health Network recently sent a news item about the FDA’s September 29 letter to LabCorp, advising it that its ovarian cancer screening test is a medical device that must be pre-approved by the FDA before it can be marketed. In response to the letter, LabCorp (NYSE:LH) announced at the end of October that it is halting sales of OvaSure.

Back in August, the New York Times ran an article on the test: Cancer Test for Women Raises Hope, and Concern

As the FDA’s letter said:

Our review indicates that this product is a device under section 201(h) of the Food, Drug, and Cosmetic Act (FDCA or Act), 21 U.S.C. 321(h), because it is intended for use in the diagnosis of disease or other conditions, or in the cure, treatment, prevention, or mitigation of disease. The Act requires that manufacturers of devices that are not exempt obtain marketing approval or clearance for their products from the FDA before they may offer them for sale….

According to our records, no such determination has been made for OvaSure™. Because you do not have marketing clearance or approval from the FDA, marketing OvaSure™ is in violation of the law. The device is adulterated under section 501(f)(1)(B) of the Act, 21 U.S.C. 351(f)(1)(B)…. The device is also misbranded under section 502(o) the Act, 21 U.S.C. 352(o)….

Here’s what National Women’s Health Network had to say about the test:

Don’t Be Fooled by OvaSure

The Food and Drug Administration (FDA) recently warned that the marketing of a new ovarian cancer test violates the laws guarding against promotion of unproven technologies, vindicating skeptics like the National Women’s Health Network, who were concerned that the test was not ready to be used for routine cancer screening. OvaSure is a test that measures six different proteins in blood samples and calculates the odds that a woman will develop ovarian cancer. The $220 test was developed by LabCorp and has been available since late June.

When ovarian cancer is detected in its earliest stages, more than 90 percent of women survive at least five years. When the cancer is discovered in its late stages, after it has spread beyond the ovaries, only about 30 percent of women survive five years. There is currently no effective screening tool for ovarian cancer, so only about 20 percent of cases are detected early. OvaSure was developed to fill this void, but the test has not yet been shown to be very effective at detecting early disease. False positives are also a serious concern. A screening test that says a woman has a cancer when she doesn’t is dangerous because it subjects women to unnecessary worry and sometimes even surgery, including the possibility of unnecessary removal of a healthy ovary. (It shouldn’t happen, but it does.)

The NWHN worked hard with other consumer safety organizations and with our allies in Congress to enact FDA reform in 2007 sending the FDA a clear message that the agency should be tougher in enforcing its rules to protect women from ineffective drugs, devices and tests that could put their health at risk.

LabCorp has been told by the FDA that it must meet premarketing approval requirements before getting the okay to market Ovasure. Thanks to everyone who helped us send a message that women want safe and effective health products, as well as speedy approvals. We urge Labcorps, and others trying to find a good screening test for ovarian cancer, to do the research necessary to prove the tests will meet the FDA’s standards and actually improve women’s health. Women are waiting.