01/24/17

Herding Pharma “Cats”

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The Chinese government released a report in September of 2016 by the State Food and Drug Administration (SFDA) that found fraudulent clinical trial practices on a massive scale. The SFDA concluded that over 80% of clinical trial data was fabricated. The scandal was the result of a “breach of duty by supervision departments and malpractice by pharmaceutical companies, intermediary agents and medical staff.” More than 80% of the applications for the mass production of new medications have been cancelled, with warnings by the SFDA that further evidence of malpractice might still emerge.

Radio Free Asia also reported the SFDA indicated much of the clinical trail data was incomplete at best. But it also failed to meet basic analysis requirements or was untraceable. “Some companies were suspected of deliberately hiding or deleting records of adverse effects, and tampering with data that did not meet expectations.” Apparently, this came as no surprise to industry insiders. “Clinical data fabrication was an open secret even before the inspection.”

Many of the new drugs were combinations of existing ones. Clinical trial outcomes were written beforehand, and their data presented so it agreed with the fabricated outcomes. A doctor at a top Chinese hospital said the problem lay with the failure to implement regulations governing clinical trial data. “Guangdong-based rights activist Mai Ke said there is an all-pervasive culture of fakery across all products made in the country.” Reporting for Pharmafile, Ben Hargreaves said:

The root of the issue is then not regulation, with regulation for clinical trials running on similar lines to Western practises, but in the lack of adherence to them. China’s generic drug industry has struggled with quality problems and therefore there is a temptation for companies to manipulate data to meet standards. The report found that many of the new drugs were found to be a combination of existing drugs, with clinical trials outcomes written beforehand and the data tweaked to fit in with the desire outcomes.

Sadly, clinical trial problems are not unique to China. An editorial published in the British journal The Lancet Psychiatry described multiple issues beginning with how subjects are recruited, moving on to determining what the control group should be, and ultimately defining meaningful outcome measures. Sometimes, trial recruits receive “care” they didn’t agree to. “Researchers and ethics review boards need to examine the ethical arguments and practical procedures from other areas of medicine where consent is problematic.” If such trials are done, regular and rigorous monitoring is essential. Patient safety and autonomy needs to be a priority.

In his discussion of the editorial, Justin Carter elaborated on one of the problems with recruiting subjects. An individual was recruited into a study on three antipsychotics while under a forced commitment order from a judge. “The psychiatrist who recruited him was in charge of the study and was his treatment provider and was also empowered to report on the patient’s progress to the judge.” The individual died by suicide during the drug trial.

The work of Irving Kirsch and others has shown the problem with inert placebos (sugar pills). The side effects from medication make it easy for participants to guess which study group they are in.

And when the trial is over and the data in, do the outcome measures really provide something meaningful for people’s lives? If the ultimate goal is for people to fell better and resume their prior level of functioning, should outcome measures by primarily patient self-reports, clinical assessment, or differences shown by imaging or the as-yet-to-be-clearly-identified biomarkers?

Given the problems running and interpreting psychiatry trials, it is essential to learn how even the most successfully tested interventions work in real clinics with the broad patient population. Implementation, uptake, and effectiveness in real-life settings must be analysed, and delivery of new innovations modified accordingly. Future research should be thought of not as a plain linear process from innovation to trial to implementation, but as a virtuous circle where research feeds into the clinic and vice versa.

Another issue pointed to by Carter was the validity and reliability of the diagnosis or classification system used to determine who to include and who to exclude from the trials. The DSM system, now in its fifth edition (DSM-5), is the current “bible” for assessing and diagnosing problems the psychiatric medications in clinical trials are supposed to “treat” in the U.S. Yet there have been questions about the reliability and validity of the DSM dating from an argument raised by Robert Spitzer and others in the 1970s that ushered in changes still embedded in the DSM-5. Rachel Cooper gave a brief history of the reliability questions with the DSM in “How Reliable is the DSM-5?” You can also refer to “Psychiatry Has No Clothes,” “Where There’s Smoke …”, and  “The Quest for Psychiatric Dragons,” Parts 1 and 2.

A few weeks before the release of the DSM-5, Thomas Insel, then the NIMH Director, announced the NIMH would be “reorienting” its research away from DSM categories. The agency’s new approach is called the Research Domain Criteria (RDoC) project. For now, RDoC is a research framework and not a clinical tool. But NIMH has high hopes for it: “RDoC is nothing less than a plan to transform clinical practice by bringing a new generation of research to inform how we diagnose and treat mental disorders.” While Tom Insel has moved on to work for Alphabet (Google), RDoC is alive and well within NIMH. You can keep up with news about RDoC on the “Science News About RDoC.”

The Science Update for February 16, 2106 noted the March 2016 issue of the journal Psychophysiology would be devoted to the RDoC initiative. Dr. Bruce Cuthbert said the special issue was a unique opportunity for researchers to engage with one another and reflect on work being done in various laboratories throughout the country. He thought it was encouraging to see many investigators already engaged in the kind of work RDoC advocates. “What this shows is that while the RDoC acronym may be new, the principles behind RDoC are certainly not new to psychiatric research.”

If the principles behind RDoC are not new to psychiatric research, how can it bring “a new generation of research to inform how we diagnose and treat mental disorders” in order to transform clinical practice? It sounds a lot like using the same deck of cards to just play a new card game. RDoC may not be the transformative framework it’s touted to become.

Added to these issues is the failure of pharmaceutical companies to publically report the results of clinical trials, as they are required by law to do. New reporting rules will take effect on January 18, 2017. But advocates for transparency in clinical research have cautioned the success of the new rules will depend upon the willingness and vigor of government enforcement of those rules. The failure to enforce the existing rules, which went into effect in 2008, led to widespread noncompliance with reporting requirements. If the FDA had fined the violators, they could have collected an estimated $25 billion.

Reporting for STAT News, Charles Piller said studies have indicated only a small fraction of trials will comply with the law. Yet there are no current plans to increase enforcement staffing at the FDA and NIH. That’s a big problem, according to Ben Goldacre, an advocate for full disclosure in clinical research. Francis Collins, the NIH director said they are serious about this and will withhold funds, if needed. “It’s hard to herd cats, but you can move their food, or take their food away.”

The legislation that created ClinicalTrials.gov emerged from numerous cases of drug manufacturers withholding negative trial results, making drugs look more effective and less harmful. Efforts to market the antidepressant Paxil for teenagers more than a decade ago stimulated the push for better reporting. A recent analysis in the journal BMJ found that GlaxoSmithKline, Paxil’s manufacturer, failed to disclose 2001 data showing the drug to be no more effective than a placebo, and was linked to increased suicide attempts by teens.

Writing for Time, Alexandra Sifferlin reported on a new study that suggested many of the medical reviewers for the FDA go to work for the drug companies they oversaw while working for the government. One of the study’s authors said: “I don’t think there is overt collusion going on, but if you know in the back of your mind that a major career opportunity after the FDA is going to work on the other side of the table, I worry it can make you less likely to put your foot down.”

Returning to the Francis Collins metaphor, it seems that the willingness to try and herd Pharma cats is dependent on whether or not you are afraid they will scratch you in the attempt.

12/2/16

Pharma and Advertising

© Maksim Kabakou | 123rf.com

© Maksim Kabakou | 123rf.com

The FDA recently held public hearings on the off-label advertising of approved medications and medical devices on November 9 and 10, 2016. “FDA is engaged in a comprehensive review of its regulations and policies governing firms’ communications about unapproved uses of approved/cleared medical products, and the input from this meeting will inform FDA’s policy development in this area.” There were specific questions asked at the hearing, but the FDA was also interested in “any other pertinent information participants would like to share.” If you weren’t able to be in Maryland for the hearing, electronic or written comments will be accepted until January 9, 2017. A videotape of the hearing will be available for one year afterwards.

Your initial reaction may be one of “Boring!” That is unless you are aware of the crossroads we are approaching with regard to the off-label advertising of medications and medical devices. On March 8, 2016, the FDA made a settlement agreement with the pharmaceutical company Amarin that allows the company to promote its drug Vascepa for off-label use. What is this important breakthrough medication? Vascepa is prescription strength fish oil. This action was the outcome of a struggle between Amarin and the FDA going back several years.

Amarin wanted to widen the population for whom they could recommend Vascepa to include patients with different cardiovascular diseases—patients other than what Vascepa was initially approved to treat. But the FDA ruled against their request. Amarin’s stock price took a nosedive. Concerned with how their investors were reacting, the company fought back by suing the FDA. Then in August of 2015, a judge ruled that Amarin could market its drug to the broader population. He also ruled the company could claim that Vascepa “may reduce the risk of coronary heart disease.” This was despite the fact that the FDA had called the claim misleading, as there was “supportive but not conclusive research” to that effect.

Amarin successfully argued that it had a First Amendment right to market its drug for a broader patient group, “despite the lack of regulatory approval and the lack of evidence of an outcomes benefit for patients.” Justin Karter noted how the FDA settlement strikes at the heart of the drug regulatory system in the U.S. Amarin argued that companies should have the right to market their products consistent with what “a judge would consider to be neither false or misleading.” Be clear on what Amarin was saying. A judge, not the FDA, should rule on whether or not the marketing claims by a pharmaceutical company for their product were truthful and not misleading.

Amarin argued that this system is unconstitutional, and that companies should instead be allowed to market their products in any way that a judge would consider to be neither false nor misleading.

Commenting on the FDA settlement agreement in Amrain Pharma v. U.S. Food & Drug Administration, lawyer and mental health advocate Jim Gottstein said he thought that for all practical purposes, the FDA ban against off-label promotion of drug companies was dead. He noted that the ruling in the Amarin case was based upon a 2012 decision in Unites States v. Caronia that reversed a criminal conviction for off-label promotion.

In light of the settlement I think it is fair to ask where things stand with the FDA’s enforcement of its ban against off-label promotion and Department of Justice prosecutions of drug companies for off-label promotion leading to false claims.  I think the ban against off-label promotion is dead for all practical purposes.  The FDA could try and get a different ruling in another circuit and, if successful, ask the Supreme Court to rule, but since it didn’t ask the Supreme Court to take the case in Caronia, it doesn’t seem likely that it has any intention of trying to overturn Caronia. This will give the drug companies free rein for off-label promotion.  Of course, anything that is false or misleading is still grounds for charges, but that is a far harder case to make.

So if this is the supposed future for off-label drug advertising unless there is some radical change by Congress, let’s now take a look at the past—what has been taking place under the existing FDA rules. In his book Saving Normal, Allen Frances published a chart that he called the drug company “hall of shame.” Prepared by Melissa Raven, PhD, it listed the fines and settlements by Pharma companies for off-label promotion, marketing and fraudulent misbranding of 20 well know pharmaceuticals.

Here is a sampling of the companies and their total fines and settlements between 2004 and 2012 recorded in the Saving Normal chart. The fines and settlements listed below combine both civil and criminal cases. Johnson & Johnson ($1.44 billion); GlaxoSmithKline ($3 billion); Abbott ($1.5 billion); Novartis ($422.5 million); Forrest ($313 million); AstraZeneca ($520 million); Pfizer ($2.3 billion); Eli Lily ($1.415 billion); Bristol-Myers Squibb ($515 million); Purdue (almost $635 million). I think it’s clear why Pharma is going after the FDA. The sum total in fines and settlements from the chart was $12.06 billion in fines and settlements between 2004 and 2012.

On March 31, 2016, the nonprofit organization Public Citizen published an updated analysis of all major financial settlements and court judgments between pharmaceutical companies and the federal and state governments. The time period covered by their analysis ran from 1991 through 2015 and included 373 settlements for a total of $35.7 BILLION. Financial penalties have declined sharply since 2013. The most striking decrease occurred with criminal penalties. “For 2012 and 2013 combined, criminal penalties totaled $2.7 billion, but by 2014-2015, the total had fallen to $44 million, a decrease of more than 98%.”

From 1991 through 2015, GlaxoSmithKline and Pfizer reached the most settlements—with 31 each— and paid the most in penalties, $7.9 billion and $3.9 billion respectively. Six additional companies, Johnson & Johnson, Merck, Abbott, Eli Lilly, Teva, Schering-Plough, Novartis, and AstraZeneca paid more than $1 billion in financial penalties. Six of the above eight were listed in the top 14 pharmaceutical companies by global sales in 2014. Thirty-one companies entered repeat settlements. Pfizer (11), Merck (9), GlaxoSmithKline, Novartis, and Bristol-Myers Squibb (8 each) finalized the most federal settlements. It seems these fines were simply the cost of doing business.

Financial penalties continued to pale in comparison to company profits, with the $35.7 billion in penalties from 1991 through 2015 amounting to only 5% of the $711 billion in net profits made by the 11 largest global drug companies during just 10 of those 25 years (2003-2012). To our knowledge, a parent company has never been excluded from participation in Medicare and Medicaid for illegal activities, which endanger the public health and deplete taxpayer-funded programs. Nor has almost any senior executive been given a jail sentence for leading companies engaged in these illegal activities. Much larger penalties and successful prosecutions of company executives that oversee systemic fraud, including jail sentences if appropriate, are necessary to deter future unlawful behavior. Otherwise, these illegal but profitable activities will continue to be part of companies’ business model.

Since the U.S. approved direct-to-consumer advertising of prescription drugs in 1997, there has been a dramatic increase in spending on pharmaceuticals. A New England Journal of Medicine study by Donohue, Cevasco and Rosenthal in 2007 found that spending on pharmaceutical promotions increased from $11.4 billion in 1996 to $29.9 billion in 2005. This was a 330% increase. Promotion to physicians was still the primary marketing strategy, but spending on direct-to-consumer advertising increased both in absolute terms and as a percentage of pharmaceutical sales.

Becker and Midoun recently published an article that investigated the effects of direct-to-consumer advertising (DTCA) on patient prescription requests in the Journal of Clinical Psychiatry. Of the 989 articles they initially identified, they read full-text reviews of 69 articles, but only found four that met their inclusion criteria for investigating the consequences of these ads on prescription rates and treatment quality. They conclusion was: “Findings suggest that DTCA requests are typically accommodated, promote higher prescribing volume, and have competing effects on treatment quality.” They called for methodlogically stronger studies to increase the confidence in their conclusions.

Reporting for Mad in America on the study, Justin Karter noted where the U.S. is only one of three countries globally that allows DTCA. He said the pharmaceutical industry spent $3.83 billion on DTCA in 2013 and $4.53 billion in 2014. He also noted that the American Medical Association (here) and the American Society of Health-System Pharmacists (ASHP) (here) have called for a ban on DTCA. The AMA Board Chair, Patrice Harris, commented that physicians were concerned with the negative impact of DTCA and the role marketing costs play in fueling escalating drug prices. “Direct-to-consumer advertising also inflates demand for new and more expensive drugs, even when these drugs may not be appropriate.” The ASHP approved a new policy at their 2016 meeting that would advocated for Congress to ban DTCA for prescription drugs and medication-containing devices.

Pharmaceutical companies have whittled away at existing FDA regulations that restrict direct-to-consumer advertising. And they seem to be poised to begin an era of DTCA that will massively overshadow what has already taken place under the existing rules. Healthcare organizations representing physicians and pharmacists in the U.S. have publically voiced their opposition to DTCA. Individuals and organizations have an opportunity to voice their concern for this practice, which is implicated in the rising cost of healthcare and medications. Congress also has an opportunity to enact new legislation that would eliminate this predatory marketing practice. But it will have to overcome the horde of lobbyists—more than there are members of Congress—and the $272,000 in campaign donations Pharma spent per member of Congress in 2015.

12/31/15

Medieval Alchemy

© algolonline | 123rf.com

© algolonline | 123rf.com

Three years after the publication of the fourth edition of the DSM in 1994, the US became the only country in the world to allow direct to the consumer advertising of pharmaceuticals. Now there’s New Zealand. Soon after the approval, pharmaceutical advertising was everywhere in the US. Over the next decade, from 1997 to 2007, drug companies tripled their spending on marketing. Everyday problems were being portrayed as unrecognized psychiatric disorders. The chair of the DSM-IV, Allen Frances, admitted they had failed to anticipate how easily their manual could be utilized to promote pharmaceutical sales. They were not able to stem the flood of “false demand” instigated by the marketing done by drug companies. “Within a few years, it was clear the drug companies had won and we had lost.”

We should have been far more active in educating the field and prospective patients about the risks of overdiagnosis. There should have been prominent cautions in DSM-IV warning about overdiagnosis and providing tips on how to avoid it. We should have organized professional and public conferences and educational campaigns to counteract drug company propaganda. None of this occurred to anyone at the time. No one dreamed that drug company advertising would explode three years after the publication of the DSM-IV or that there would be the huge epidemics of ADHD, autism, and bipolar disorder—and therefore no one felt any urgency to prevent them. . . . We missed the boat. (Allen Frances, Saving Normal, p. 74)

Frances said the evidence for this diagnostic inflation is clear. There has been a fortyfold increase in childhood bipolar disorder. Autism diagnoses have increased twentyfold. “Attention deficit/hyperactivity has tripled; and adult bipolar disorder doubled.” The result has been huge profits for the drug companies.

At the very top of the Pharma hit parade are the antipsychotics at a resounding $18 billion a year. Antidepressants produce a hardy $12 billion a year, despite the fact that many are now off  patent and sold in cheaper generic versions. Fifteen years ago, stimulants were a rounding error in drug company sales at a measly $59 million a year. Now with direct-to-consumer advertising and heavy marketing to doctors, sales have been juiced up to a hefty $8 billion a year. And because primary care doctors love to prescribe them, antianxiety agents are eight in sales among drug classes—even though they probably do much more harm than good. (Saving Normal, p. 105)

Patients regularly misdiagnosed themselves and asked their doctor for “the magic pill that would correct their chemical imbalance,” just as the advertisements suggested. And as requested, doctors prescribed the medications. “Patients who requested a drug they had seen advertised were seventeen times more likely to walk out of the office with a prescription.” Primary care physicians (PCPs), such as general practitioners, obstetrician-gynecologists and pediatricians, now prescribe most of the psychiatric drugs in the US.

Using data from August 2006 to July 2007, Ryan DuBosar noted in “Psychotropic drug prescriptions by medical specialty” that 59% of the psychotropic prescriptions were written by PCPs. Breaking down the drug by class, PCPs prescribed 37% of the antipsychotics, 52% of the stimulants, 62% of the antidepressants and 65% of the anxiolytics (anti-anxiety meds). Frances said: “Too often, drugs are used promiscuously in a way that approximates the quackish practice of medieval alchemists.”

On November 17, 2015, the American Medical Association (AMA) adopted a new policy that calls for a ban on direct to the consumer advertising of prescription drugs. The new policy calls for a physician task force and launching an advocacy campaign to promote prescription drug affordability.

The AMA Board Chair-elect, Patrice Harris, said the vote reflects concerns among physicians about Pharma’s commercially-driven promotions and the impact of marketing costs in escalating drug prices. She said direct-to-consumer advertising also created a demand for new and more expensive drugs, even when these drugs may not be appropriate. “Patient care can be compromised and delayed when prescription drugs are unaffordable and subject to coverage limitations by the patient’s health plan. In a worst-case scenario, patients forego necessary treatments when drugs are too expensive.”

Reporting for Reuters, Susan Kelly noted that the AMA did not say how the ban could be overturned. There have been a series of court decisions determining that the ads are a form of commercial speech protected by the U.S. Constitution. PhRMA, the largest trade group for the pharmaceutical industry in the US, said the ads increase consumer awareness of available treatments for diseases. PhRMa spokesperson, Tine Stow said: “Providing scientifically accurate information to patients so that they are better informed about their health care and treatment options is the goal of direct-to-consumer pharmaceutical advertising about prescription medicines.” REALLY?

Allen Frances said that Big Pharma seems to feel it is above the law. “Almost all of the companies have absorbed huge fines and even criminal penalties as punishment for their illegal sales practices. He published a chart in Saving Normal that he referred to as the drug company hall of shame. It contained information on fines and settlements by Pharma for off-label promotion (which is illegal at this time) as well as shady marketing and fraudulent misbranding. The sum total of the fines between 2004 and 2012 was $12.06 billion.

Yet a Pharma company has been in court attempting to assert that it has “a constitutional right to share certain information about its products with doctors.” The drug companies have been increasing their pressure on the FDA to relax its guidelines around off-label marketing. See “Pharma Goes to Court” for more on this issue.

Frances said it is our fault that we allowed drug companies to prey on our weakness. “Diagnostic questions should be decided by what is best for the patient, not what is best for the doctor or the APA [American Psychiatric Association] or Pharma or the consumer group.” All this could be reversed if we had the political will to do so. He proposed fourteen ways to tame Pharma. The top six were:

  • No more direct-to-consumer advertising on TV, in magazines, or on the internet.
  • No more drug company-sponsored junkets, dinners, promotional gifts, or continuing medical education for doctors or medical students.
  • No more financial support for medical professional organizations.
  •  No more beautiful salespeople congregating in the doctors’ waiting room.
  • No more free samples.
  • No more off-label marketing.

These changes strike at the heart of Pharma’s marketing strategy, so it won’t be easy to get Congress to approve the changes. Pharma outspends all other industries in its lobbying efforts. Since 1998, the pharmaceutical industry has spent $3,201,510,687 lobbying Congress. So far in 2015 Pharma has spent $178,863,490. Annually they outspend all other industries. You have to go back to 2005 to find annual spending under the to date figure for 2015. See OpenSecrets.org for more information on this issue.

07/29/15

Pharma Goes to Court

© Satori | 123RF.com

© Satori | 123RF.com

Okay, stay with me on this one. I want to talk about some jousting going on in the court system between Pharma and regulatory agencies, like the FDA. Amarin Corporation is suing the FDA, saying that the FDA violated its first amendment rights to free speech. The company argued that it has “a constitutional right to share certain information about its products with doctors.” Lawyers for the company believed this was the first time a manufacturer has sued the agency before the FDA ruled against them. The future “blockbuster” at the center of this fight is an omega-3 fatty acid product derived from fish called Vascepa. That’s right prescription strength fish oil.

As a matter of fact, according to Katie Thomas of The New York Times, Vascepa is the only existing product for Amarin. The FDA approved Vascepa for patients with extremely high levels of triglycerides, which are linked to heart disease. When the company sought to expand the drug’s approved reach to individuals with severe levels of triglycerides, the FDA denied its request. Lawyers for the company claim the company is not trying to market Vascepa to a wider population of patients than it was approved for, which is illegal. Amarin merely wants to make statements about its product that manufacturers of fish-oil supplements make—namely that there is “supportive but not conclusive research” that shows fish oil products like Vascepa may reduce the risk of coronary hear disease.

A lawyer for Amarin pointed out where doctors are already prescribing Vascepa off-label, which is legal for doctors to do once the FDA approves a drug for any purpose. “Those doctors who are already prescribing off-label need more information, not less, about what their treatment options are.” John Sullivan said on Drug and Device Law, that the content of Amarin’s supporting brief was convincing. In addition to the “truthful, non-misleading statements it wants to provide to healthcare workers, it wants to provide the results of its ANCHOR clinical trial and other peer-reviewed articles on the connection between the active ingredient in Vascepa and coronary risk.

But is all this legal dancing around just about the right of a relatively small biopharmaceutical company to make the same claims about its prescription drug that dietary supplement companies can make about their fish oil products?

Toni Clarke, writing for Reuters, noted where drug companies have been increasing their efforts to pressure the FDA to relax its guidelines since a 2012 decision  (2-1) from the Second Court of Appeals overturned the conviction of a sales representative for Orphan Medical, who was caught talking to physicians about off-label uses for the narcolepsy drug, Xyrem. The court said truthful and non-misleading off-label “speech” was protected by the First Amendment. “Pharmaceutical companies are citing the Caronia and similar rulings to pressure the FDA to let them talk more freely about off-label use.”

A coalition of pharmaceutical companies known as the Medical Information Working Group has petitioned the FDA to “’adequately justify and appropriately tailor its regulatory regime in light of Caronia and similar rulings.” This coalition includes Pfizer, Sanofi, Novartis AG, Johnson & Johnson, Eli Lily and Co., GlaxoSmithKline, Purdue Pharma, and Bayer Healthcare Pharaceuticals. What’s at stake is the right of manufacturers to attempt to persuade physicians to use their products for unapproved uses. This would be a potentially serious weakening of the FDA’s regulatory authority. Oh, and it could mean billions of dollars in potential sales for Pharma.

The FDA sent a letter to Amarin, essentially saying that it did not have concerns with most of the information Amarin proposed to communicate to doctors. The FDA pointed to existing guidance documents that indicated Amarin could distribute the results of its ANCHOR clinical trial results through peer-reviewed articles. Further, it said Amarin could communicate summaries of those trail results, but not in marketing materials or through sales reps.

Then on June 23, 2015, the FDA filed its brief in response to Amarin’s Motion for Preliminary Injunction. The brief called the lawsuit a frontal assault on the framework for new drug approval, rather than a narrower as-applied constitutional challenge. Lisa Baird, writing for ReedSmith, further noted where the FDA felt that if successful, the Amarin litigation “has the potential to establish precedent that would return the country to the pre-1962 era when companies were not required to prove that their drugs were safe and effective for each of their intended uses.”

At the heart of the matter is the distinction made by the FDA between drugs and dietary supplements. The FDA brief noted that Amarin ignored “the critical reality that drugs present markedly different considerations from dietary supplements.” After citing several legal rulings in support of this claim, the FDA said that Amarin wanted to market Vascepa as a drug intended to treat patients who are already being treated with statins, but continue to be at risk for cardiovascular disease. “Yet, FDA has found on multiple occasions that the heart disease claim did not meet the statutory standard of significant scientific agreement as the claim is based on ‘less persuasive studies.’” The potential harm posed by drugs is presumably much greater than that posed by dietary supplements.

These considerations amply justify a more cautious approach to drug approval and promotion, and the applicable statutory scheme recognizes this necessity. Unlike drugs, there is no statutory requirement of premarket approval for dietary supplements to be distributed. See 21 U.S.C. § 301 et seq. In addition, as a result of Pearson, claims about dietary supplements are held to a much lower standard (credible evidence) than the robust evidentiary requirement for drugs (substantial evidence) or the intermediate standard that FDA applies to reprints. See 21 U.S.C. § 355(d) & (e); Woodcock Decl. ¶¶ 31-32. Unlike for drug claims, qualified health claims “can be made [for dietary supplements and foods] under some circumstances even when the weight of the scientific evidence is against the claim, provided there is some credible evidence supporting it.” Woodcock D ecl. ¶ 33. Indeed, the June 5 Letter advised Amarin that if it “were to repackage and re-label [its] product as a dietary supplement” and ensure that other relevant conditions were met, “FDA would not object to your inclusion on that dietary supplement of the” heart disease claim. June 5 Letter at 10. Plaintiffs thus conflate two separate regulatory regimes and seek to make Amarin subject only to the aspects of each regime that it finds convenient—an approach that is unsupported by law and contrary to logic and sound public health policy.

This is an important and potentially a serious game changer in FDA attempts to protect the public from the growing evidence of the harmful marketing tactics of Pharma. This jousting between Amarin and the FDA is taking place in the context of the recent approval of “The 21st Century Cures Act,” which was unanimously approved by the House Energy and Commerce Committee on May 21, 2015. Toni Clarke reported that language in the bill adds pressure on the FDA to relax its guidelines.

Allen Frances, in his book Saving Normal, published a chart that he called the drug company “hall of shame.” Prepared by Melissa Raven, PhD, it listed the fines and settlements by Pharma companies for off-label promotion, marketing and fraudulent misbranding of 20 well know pharmaceuticals. Most of the companies noted above who are part of the Medical information Working Group were listed there. Here are the companies and their total fines and settlements between 2004 and 2012 recorded in the table in Saving Normal. The fines and settlements combine both civil and criminal cases. Johnson & Johnson ($1.44 billion); GlaxoSmithKline ($3 billion); Abbott ($1.5 billion); Novartis ($422.5 million); Forrest ($313 million); AstraZeneca ($520 million); Pfizer ($2.3 billion); Eli Lily ($1.415 billion); Bristol-Myers Squibb ($515 million); Purdue (almost $635 million). I think it’s clear why Pharma is going after the FDA. The sum total in fines and settlements from the chart was $12.06 billion between 2004 and 2012.

The FDA announced that it plans to hold a public meeting this summer to address drug company concerns with restrictions on what they can say about off-label use of drugs. But as of the beginning of July, I could find no indication of a set date and time for the public meeting. Perhaps the FDA decided to delay scheduling the meeting until there was an indication what would happen with the 21st Century Cures Act. They may also want to see further reaction to its June 23, 2015 brief filed in response to Amarin’s Motion for Preliminary Injunction.

If I wanted to build case law precedents to justify my constitutional right to share certain information about my pharmaceutical products with doctors, I think I’d first try to have the courts rule in favor of a product like pharmaceutical grade fish oil. It’s already sold as a dietary supplement and there are hardly any known side effects. If successful, I’d build on it and the Caronia case by filing additional litigation in an attempt to cut off the FDA regulations against off-label promotion and marketing of pharmaceuticals at the knees.