Posted today by the PostScript blog at Community Catalyst:

New Legislation to Protect and Improve the American Drug Supply

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

The last year has been a roller coaster-ride of both successes and set-backs in the fight to eliminate pay-for delay settlements. These multi-million dollar sweetheart deals have been used more and more by brand-named drug makers to get their generic competitors to agree to delay bringing affordable generics to the market.

A bill to ban these agreements was included in the House’s health care reform proposal last fall, and a similar measure was supported by the White House and considered by the Senate. Unfortunately, the Senate’s procedural and jurisdictional rules kept the measure from being included in the national health reform bill enacted in March.

Undeterred, leaders in the House then included the measure in an appropriations bill approved on July 1^st. But the Senate passed one appropriations bill on July 22 without the provision. In the aftermath of this setback, consumer champion Senator Herb Kohl (D-WI) and others succeeded in including this vital reform as an amendment to the FTC’s budget authorization. Kohl and others then  overcame the next major hurdle yesterday, narrowly stopping  drug industry lobbyist efforts to strip the measure in the Senate Appropriations Committee.

Yesterday’s vote was a dramatic one.  Senator Arlen Specter (D-PA) introduced an amendment to remove the pay-for-delay provision from the Committee bill. When four Democrats voted with Specter  to strip away the pay-for-delay provision, the AP reports that:

“Drug company lobbyists in the audience thought they had the vote won, provided they could win over every panel Republican. But Sen. Richard Shelby, R-Ala., voted against the drug companies, helping give Kohl and Durbin [the author of the Appropriations Bill] a surprise win.”

Recent settlements shielding $9 Billion in drug spending from generic competition

The Federal Trade Commission (FTC), which has consistently challenged these anti-competitive agreements in the courts and through testimonies before Congress, called yesterday’s vote a significant victory. FTC chairman Jon Leibowitz testified before Congress earlier this week that these types of pay-for-delay agreements, which delay the entry of generic drugs, are becoming more common (see graph). Legal decisions permitting these agreements have led to their proliferation from none in 2004 to a former high of 19 such agreements in 2009. The FTC notes that in just the first 9 months, the number of pay-for-delay settlements in fiscal year 2010 has already topped last year’s record high. 

Graph: Federal Trade Commission

The FTC’s preliminary analysis of the agreement filed this fiscal year concludes that 21 pay-for-delay agreements entered into this year are protecting $9 billion in prescription drug sales from generic competition. Combined with the earlier agreements in effect, this could mean that as much as $29 billion in annual spending on drugs are improperly shielded from generic challengers.  That is a significant loss of possible savings.  The FTC estimates (conservatively, in our opinion) that these settlements are costing consumers and our health system at least $3.5 billion a year.

FTC has continued to raise the alarm about these settlements, and their effect upon consumers. In a press release coinciding with testimony before Congress, FTC Chairman Jon Leibowitz summed it up:

“That’s almost an epidemic,” Chairman Leibowitz said, “and left untreated, these types of settlements will continue to insulate more and more drugs from competition. Every single FTC Commissioner, going back through the Bush and Clinton administrations, has supported stopping these unconscionable agreements.”

On the legal front, PAL continues to support efforts to do away will these settlements. PAL and AFSCME District Council 37 filed an amicus brief in May in support of the Second Circuit’s reconsideration of the legality of these agreements in the Cipro litigation. And the PAL-member lawsuit challenging the pay-for-delay settlements concerning Provigil continues.

FTC Chairman Leibowitz testified that some of these recent events, such as the Second Circuits Cipro decision and the fact that the House has already passed a ban on these settlements, gives him “reason to believe that the tide may be turning, both in the courts and in Congress.” Yet, Chairman Leibowitz wisely cautioned that bringing about such a reform through the Courts will take time, which means that  “legislation would be the most effective way to stop these deals.”

Thus the successful Senate Committee vote yesterday “means that consumers are one step closer to saving billions on their prescription drugs” according to Leibowitz.  And help can’t come too soon.  The bill’s Senate sponsor, Senator Herb Kohl, points out why: 

“The cost of brand-named drugs rose nearly ten percent last year. In contrast, the cost of generic drugs fell by nearly ten percent. At this time of spiraling health care costs, we cannot turn a blind eye to these anticompetitive backroom deals that deny consumers access to affordable generic drugs.”

We view yesterday’s decision as a crucial step  to put legislation in place to end these agreements and foster consumer access to affordable generic drugs.

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

(This is the first in a two-part blog. Read tomorrow when we look at how industry and other stakeholders weighed in.)

How clear does risk information need to be in direct-to-consumer drug ads? That’s the question the FDA is getting closer to answering as stakeholders weighed in this week on the agency’s proposed rules for presenting risk in broadcast ads.

Twenty-two organizations from the PAL Coalition and other supporting groups joined PAL in submitting comments that support the agency’s new proposal to make risk information clear, conspicuous, and neutral in TV ads. The groups also suggested the FDA require that risks be quantified in ads and that the overly-scientific talk be toned down to match the comprehension of the viewer who would have the most trouble understanding the ad.

Many of the provisions in this year’s proposed rule do reinforce the handling of risk information that FDA proposed in last year’s draft guidance. But they are clearer and more concrete, and would go further than the agency’s current standard of “fair balance,” in which drugmakers are only required to present risk as clearly as they present benefits. Specifically, the proposed rules would require that ads use everyday language that is easily readable when in writing and is presented slow enough and prominent enough, whether in writing or audio form, to be easily understood by a consumer viewing the ad. The FDA also proposed a rule that would ban any distracting sounds or images in broadcast prescription drug advertisements.

A step back on why all this matters: remember that the U.S. is one of only two countries that allows drugs to be advertised on TV at all (New Zealand is the other).  And it’s a relatively recent allowance—only in 1997 did the loosening of an FDA regulation about how the major statement about a drug is presented open the floodgates to the sleep butterflies, allergy bees, and PMS symptom balloons.

As was shown by the PAL cases on Vytorin-Zetia, Nexium, Vioxx and Ketek, those changes came with controversy and human costs. Rofecoxib, or Vioxx, was heavily advertised to consumers and physicians in its first year before it was pulled from market after being linked to between 35,200 to 52,800 deaths and 88,000 to 140,000 heart attacks in the US. This caused the Institute of Medicine and other experts to call for an end to DTCA for new drugs, whose side effects are often not known (or in Vioxx’s case, suppressed) until years after they appear on the market.

The link between DTCA and increased prescribing of newer, less-tested drugs has been well-documented, and policymakers, regulators and academics have all expressed concern that the FDA’s inability to regulate and oversee broadcast ads has put the public’s health at unnecessary risk.

But despite this concern and growing evidence that drug ads carry risks beyond the speed-read ones, drug companies came up short on proving public health benefits to their current ad style or offering new evidence-based ideas for presenting risk info in a clear and neutral way. We’ll take a look at what they said tomorrow. Short of all out banning DTCA, the FDA must determine the appropriate standards to best protect the public.

What else could the FDA do?
In addition to offering support to the proposed rules, PAL suggested additional steps that could further enhance the clarity of ads and thus further protect consumers. PAL urged the FDA to address the widely-held myths that the FDA approves all TV ads, and that the government only lets drugs that are “really safe” be advertised on TV, by requiring a disclaimer that “FDA has not approved this ad” for all ads that have not been pre-approved, and including the adverse event hot-line “Medwatch” number in all TV ads.

Though PAL fully supports FDA’s increased vigilance in regulating prescription drug ads, we noted in our comments that there are far more new ads being produced than there are FDA staff members to review these ads. It’s a big imbalance, and though increased funding and staffing of the FDA would help, delayed warning letters that appear long after an ad-buy—such as this one on Lunesta –will probably still happen.

To address this issue, the FDA should start using their authority to fine drug companies for ads that violate FDA regulations. Though fining will not increase the speed at which the FDA is able to review ads, it could potentially increase pharma’s compliance with these regulations and exact a price from noncompliant companies, even if the ad in question is no longer being aired.

Thanks to all those groups joining our comments:

The Alliance for Retired Americans
The American Federation of State, County and Municipal Employees (AFSCME)
The American Medical Student Association (AMSA)
Breast Cancer Action
California Alliance for Retired Americans (CARA)
CALPIRG
The Coalition of Wisconsin Aging Groups
Connecticut Center for Patient Safety
Connecticut Citizen Action Group
Consumers Advancing Patient Safety (CAPS)
Health Care for All
IUOE Local 4 Funds
Long Island Health Access Monitoring Project
MASSPIRG
New England Carpenters Health Fund
National Legislative Association on Prescription Drug Prices (NLARx)VPIRG
National Women’s Health Network
Oregon Health Action Campaign
Prescription Policy Choices
TeamstersCare
US PIRG

–Emily Cutrell, Prescription Access Litigation

Recently, FDA rolled out their ‘Bad Ad’ Program asking doctors and other health care providers to help ensure that ads and other promotions by the drug industry are “truthful and not misleading.”

FDA rolled out the ‘Bad Ad’ Program a month ago to enlist health care providers in recognizing and reporting untruthful or misleading promotional activities. This will help FDA’s efforts to protect consumers by identifying suspect or problematic advertising more quickly. Additionally, the program also encourages health professionals to help monitor and report some of the deceptive or illegal promotional activities taking place behind-closed doors.

To report an ad or a promotion that may be misleading or that may be suspect, contact FDA by email (BadAd@fda.gov) or phone (877-RX-DDMAC, which is 877-793-3622). Reporting can be anonymous, but FDA would like contact information for follow-up.

In 2007, the drug industry spent just over  $5 billion on direct-to-consumer (“DTC”) advertising, a quarter of their  the total  $20 billion spent on promoting drugs. According to the Government Accounting Office, the drug industry spends nearly three times as much on their sales efforts targeting physicians, nurses, and other prescribers then they spend in direct-to-consumer marketing. The ‘Bad Ad’ Program recognized this, and seeks to  increase the FDA’s ability to detect violations in the area of heaviest pharmaceutical promotion – communications between pharma reps and physicians taking place behind closed doors. Whether these are meetings in medical offices, or at other events, such as dinners, speaker training sessions, and continuing medical education events, FDA’s website sums it up like this:

Companies send us their sales aids—the booklets and campaign materials for their drug that the reps are supposed to use in the field when they talk with doctors—and we review those materials. But we have limited access to the promotional activities in these settings. That’s why we’re asking health care professionals to partner with us in our efforts to stop misleading prescription drug promotion.

According to the FDA website, enlisting the help of health care providers will help to address FDA’s own “limited ability to monitor promotional activities that occur in private.”

Consumers encouraged to report ads that are misleading:
The “Bad Ad” campaign to educate and empower health care providers complements FDA’s EthicAd campaign, which was launched earlier this year to educate consumers about misleading Direct-to-Consumer (DTC) drug promotion. The FDA has also asked for consumers to help monitor deceptive or misleading ads. 

Consumers are encouraged to report an ad they think is misleading, or that does not prevent the benefit and risk information in ‘fair balance’ by calling FDA at 301-796-1200 or writing to the FDA Division of Drug Marketing, Advertising, and Communications (DDMAC).

Consumers can also report adverse effects or reactions to drugs by calling 1-800- FDA-1088, or at http://www.fda.gov/Safety/MedWatch/default.htm

The ‘Bad Ad’ Program seems to be FDA’s latest change to revive their important role in protecting consumers from deceptive advertising of prescription drugs. Consider this: in the first 16 months under the new Obama administration, FDA has issued as many warning or enforcement letters on direct-to-consumer advertising (31) as did the Bush administration in its last 5 years at FDA’s helm.

Number of FDA enforcement letters on DTC Ads, 1997 – May 2010:

(Sources: GAO study, 2006; FDA, Jan. 1, 2006-May 31, 2010)

After years of the Bush administration’s interference with FDA efforts to monitor and protect consumers from being mislead, the FDA’s return to this vital role protecting consumers is welcome.

Bad Ad spawned by ex-execs from the industry
Interestingly, the idea for ‘Bad Ad’ came from two former drug company execs that ‘switched teams’ and now work for the FDA as advertising watchdogs. Mike Sauers, one of the bright minds behind this program, states that the goal of ‘Bad Ad’ is to teach doctors “how to be better consumers of information they receive from the drug reps.”

The FDA plans a three phase roll-out for ‘Bad Ad.’ During phase one, which began last month, the FDA will mail 33,000 informational letters to healthcare providers describing this effort. The FDA will also engage and train health care providers at select medical conventions about how to recognize misleading prescription drug promotions and how to report violations to the FDA. The FDA is also partnering with certain medical societies to distribute educational materials. For Phases 2 and 3, the FDA has said little more than that they plan to expand these efforts and update their materials, but we can envision FDA enforcing the law using their new authority to assess civil penalties and fines of up to $250,000 for each violation. 

Doctors and other health care providers should be concerned about how the drug industry has consistently deceived their drug choices through the illegal promotion of ‘off-label’ uses of prescription drugs such Zyprexa, Geodon, Lyrica, Zyvox, and Bextra. In fact, in the last six years, 5 of the 8 largest drug makers have been caught and plead guilty to such illegal off-label promotion of unapproved uses of prescription drugs. (Bristol-Myers Squibb also paid $515 million to settle claims about off-label promotion in 2007, without admitting or denying any wrongdoing.)

These activities have the potential to put a doctor’s patients at risk. But the best way for health care providers to help is by watching for misleading industry practices, and alterting FDA. ‘Bad Ad’ is one of several innovative steps FDA is currently taking to crack down on the widespread, potentially harmful promotions of prescription drugs that are misleading or untruthful.

The FDA deserves to be commended on this important effort.  Reaching out to health providers and consumers is an important start to increasing FDA’s capacity to protect consumers from misleading drug promotions. But to effectively monitor a $20-billion-dollar-a-year promotional industry, FDA needs consumer support for a significant expansion of their staffing and resources.

A surprising decision in the Second Circuit has breathed new life into legal efforts to prevent drug makers from paying to keep generics off the market.

Since 2005, the drug industry has increasingly used multi-million dollar ‘pay-for-delay’ settlements to prevent generic drugs from coming to the market. The PAL coalition has opposed this industry collusion with lawsuits on Provigil, Tamoxifen, and Cipro, and through our support for legislation (introduced by Rep. Rush and Sen. Kohl). The FTC has also been a steadfast opponent of these anti-competitive agreements and their negative impacts on consumers. Unfortunately, the ability of FTC or PAL members to challenge these settlements in the courts has been hampered by a number of unfavorable legal decisions.

The Second Circuit’s Cipro Decision

The Second Circuit’s April 29th ruling did dismiss the challenge to the ‘pay-for-delay’ settlements totaling $398 million that have prevented a generic version of Cipro from coming to the market. But the Court did so begrudgingly, and then invited the folks bringing the lawsuit to ask the Second Circuit to revisit the question of whether these settlements are legal under anti-trust protections. Even more surprising, the Court then spelled out why. 

In their decision, the three judge panel stated that a review of the binding precedent established under Tamoxifen by the full nine-judge panel for the Second Circuit (called an ‘en banc review’) may be appropriate for four reasons: First, the Court said that United States Department of Justice has urged a review of this decision saying that “Tamoxifen adopted an improper standard that fails to subject reverse exclusionary payment settlements to appropriate antitrust scrutiny.” Second, the Court found that “there is evidence that the practice of entering into reverse exclusionary payment settlements has increased since we decided Tamoxifen.” Third, the panel stated that “after Tamoxifenwas decided, a principal drafter of the Hatch-Waxman Act criticized the settlement practice at issue.” Finally, the Court noted that the Tamoxifen decision was based in no small part on the now erroneous understanding that a pay-for-delay settlement with the first generic competitor would not prevent other generic competitors from attempting to followand file suit.

The 2005 Tamoxifen decision by the Second Circuit Court of Appeals (which covers New York, Vermont, Connecticut) dismissed an FTC order challenging a pay-for-delay settlement. The Tamoxifen Court ruled the practice legal under anti-trust law, because the settlement provided drug maker AstraZeneca with no more protection from generic competition than their patent already did.

This Tamoxifen decision, along with the Eleventh Circuit’s Schering-Plough decision in 2005, and Federal Circuit’s 2008 Cipro decision, have been mounting obstacles to consumer and FTC efforts to oppose these settlements. Only the Sixth Circuit, in its 2002 Cardizem decision, has held that such agreements to “eliminate competition” are a “per se illegal restraint on trade.”

When the Appeals Courts from different US Circuits arrive at differing legal standards, the US Supreme Court should resolve this inconsistency, or ‘split’ between the Courts. Indeed, the PAL-member lawsuits concerning Cipro and Tamoxifen asked the Supreme Court to do just that, as has the FTC. So far, all of these requests have been denied. But a possible reversal in the Second Circuit might change things.

Consumers, legal and medical experts, and the Administration all file briefs in opposition to continued legality of pay-for-delay settlements

Amicus briefs in support of the request for a reconsideration of the Tamoxifen standard were filed by PAL and PAL coalition member AFSCME DC37; AARP, AMA, and the Public Patent Foundation; Consumers Union, US Pirg, Consumer Federation of America, and the National Legislative Associaton on Prescription Drug Prices. Also filing briefs were the American Antitrust Institute, the FTC, and the Department of Justice’s Anti-Trust division.

The amicus brief for the Department of Justice argues that ”by shielding most private reverse settlement agreements from antitrust liability, the Tamoxifen standard improperly undermines the balance Congress struck in the Patent Act between the public interest in encouraging innovation and the public interest in competition.”

The amicus brief from the Federal Trade Commission (FTC) added three additional reasons to those stated by the Second Circuit panel. FTC argued that the Tamoxifen standard gives drug companies an improper incentive to pay off generic drug manufacturers and protect even the weakest patents.

Next, FTC noted that the number of pay-for-delay settlements had grown since 2005, to now insulate “at least $20 billion in sales of branded drugs from generic competition.”

The FTC estimates (very conservatively in our opinion) that these settlements will continue to cost $3.5 billion a year by delaying competition from lower-priced generics, but warned that these costs may grow.

 The amicus brief submitted by PAL and PAL member AFSCME District Council 37pointed out that these settlements have cost consumers and health plans $12 billion or more each year in lost savings on generic drugs, and the costs are likely to increase as brand-name drug prices go up (as they did by 9.2 % in the year ending on March 31, 2010) while generic drug prices decline (as they did by 9.7 % during this time period.) Aside from the effect that higher costs have on reducing access to needed medicines, PAL pointed out how these settlements threaten to reduce the quality of care for consumers by limiting the drug options available to them. PAL pointed out that consumers of the drug Provigil, which is protected from generic competition by a pay-for-delay settlement, end up entering the donut hole faster and paying huge sums out of pocket when their health plans refuse to cover the drug due to its high cost.

AARP, the AMA, and the Public Patent Foundation filed a brief arguing that these settlements threaten our health care system because they undermine consumer access to generic drugs, which have, on the whole, “saved consumers over $734 billion in the last 10 years.” AARP noted that “[e]ven for those patients who are insured but who are on fixed or limited incomes, having a generic option is often the difference between having access to health care treatment and not having any treatment option at all.”

AARP’s brief warned that the Tamoxifen precedent will have long-term negative consequences on the well being of consumers because “when a generic pharmaceutical’s entry into the market is delayed, it limits treatment access to vulnerable patient populations and prolongs the difficulty that physicians have in prescribing affordable treatment options.”

An amicus brief filed by Consumers Union, Consumer Federation of America, U.S. PIRG and National Legislative Association of Prescription Drug Prices pointed out that the Tamoxifen decision allows the pay-for-delay settlements that “prevents patent challenges” which is contrary to the purpose of the Hatch-Waxman Act to “encourage[] patent challenges…..”

The American Antitrust Institute filed an amicus brief highlighting the anticompetitive nature of these settlements, and the Attorney Generals from 34 States filed an amicus noting that “the Cipro case is also of exceptional importance because the United States Supreme Court has refused to review the split between the Sixth and Eleventh Circuits.”

Industry use of these pay-for-delay settlements has driven up costs and prevented access to needed medicines for millions of consumers. This industry practice has prevented or delayed generic versions of the drugs Cipro, Provigil, Androgel, and many other drugs that amount to $20 billion of our nation’s current $278 billion in drug spending, according to the FTC.

PAL, Community Catalyst, and dozens of PAL coalition members have opposed these settlements through lawsuits and legislative advocacy. Please contact us if you would like to join in our work to oppose these anti-competitive settlements.

 — by Emily Cutrell and Wells Wilkinson

Consumer advocates concerned about the drug industry and health care fraud were given a rare treat two weeks ago — a jury trial highlighting the fraudulent drug promotions by the nation’s largest drug maker Pfizer. Even better, the jury awarded $142 Million in actual and trebled damages.

The successful trial and jury verdict on behalf of California-based insurer Kaiser Foundation Health Plan marks a significant victory for insurers and consumers, as well as a stark warning to drug makers who engage in illegal or fraudulent promotion of drugs.

Kaiser, the first insurer to try a Neurontin case against Pfizer, the world’s biggest drug maker, claimed it was forced to pay $90 million more than it should have for Neurontin.

The jury was asked to determine whether the world’s largest drug maker, Pfizer (through it subsidiary Warner-Lambert) had committed fraud by marketing the drug Neurontin for unapproved uses. That is, the jury considered whether the extensive, 10 year campaign engaged in by Pfizer’s staff of drug representatives to repeatedly promote Neurontin as an effective treatment for bipolar disorder, migraines, neuropathic pain, nociceptive pain, and for uses at very high doses, was fraudulent, in light of the fact that Pfizer knew that their own studies had never shown the drug to be more effective than a sugar pill for these unapproved uses. (Neurontin had only been approved as a treatment for epilepsy. While it is not illegal for a physician to prescribe Neurontin to treat other illnesses or conditions, it is illegal for a manufacturer to promote a drug for an unapproved, or ‘off-label’ use.)

After deliberating for two days, the jury found that sufficient evidence that New York-based Pfizer violated the both the federal Racketeer Influenced and Corrupt Organizations Act, or RICO, and California’s Unfair Competition Law by promoting four of these five off-label uses.  The jury awarded Kaiser $47.36 million in actual damages, which was trebled to $142 under provisions of the federal RICO statute.

According to Bloomberg news, the jury described the activities by Pfizer to defraud doctors and insurers as “shocking” and that one juror described Pfizer’s promotional schemes targeting doctors as “clearly a snow job.”

Pfizer attempted to hide behind the very doctors they misled, arguing that plaintiff Kaiser had not presented a single doctor who would state that they would not have prescribed Neurontin even if they knew of Pfizer’s misleading representations of omissions concerning the effectiveness of Neurontin. But the jurors aptly saw right through this ruse. Bloomberg news reports that Jury foreman Pierrotti said “no doctor wants to admit they were defrauded.”

The jury also noted that the steps that Kaiser had taken to reduce Neurontin use by covered beneficiaries after the fraud was revealed in 2002.

This verdict is a rarity in the world of drug litigation, because most cases settle long before they reach a trial or jury. It is important also as the first RICO verdict in a prescription drug case, allowing triple damages. Finally, it sets a very positive precedent for insurers and others to bring future claims against both Pfizer, and other drug companies for fraudulent promotional practices. For instance, Judge Saris previously noted that fraud findings against Pfizer in the case decided yesterday could be binding against it in future trials.

While this ruling is good news for Kaiser and some other insurers, a companion class action lawsuit by consumers before the same court continues to face significant challenges. On May 13, 2009, Judge Saris ruled that consumer and insurer classes could not be certified due to various factors related to predominance of individual factors over common facts, and issues relating to proof of causation. 

Still, a $142 Million verdict for one of thousands of insurers bodes well for future claims. Shining a light on Pfizer’s liability, this verdict illustrates how drug industry fraud and greed adds billions in unnecessary and wasteful spending to our health care costs. The lawsuit itself is an example of how litigation by non-profit insurers and consumers is necessary to confronting this waste in the private sector. For both these reasons, the successful trial merits attention by the public and policy makers, and celebration by consumer advocates.