Addressing threats to health care's core values, especially those stemming from concentration and abuse of power - and now larger threats to the democracy needed to advance health and welfare. Advocating for accountability, integrity, transparency, honesty and ethics in leadership and governance of health care.
Introduction: Big Organizations, Government Policy and Regulation, and Politics
Leaders of big health care organizations clearly are interested in influencing public policy and government regulation in ways that favor their organizations, and often indirectly themselves. We expect such leaders and organizations to make their policy preferences known. However, increasingly we have found that they take shadowy routes to their policy goals.
We have frequently discussed how large health care organizations may use less than transparent methods to advocate for their policy and regulatory objectives. Their public relations departments may fund patient advocacy organizations and medical societies that support these objectives, so-called third-party strategies. They may fund distinguished professionals and academics as key opinion leaders for the same purposes. Often they do this in systematic ways so that there efforts amount to stealth advocacy or stealth lobbying campaigns.
Even more concerning is organizational support of the revolving door. Top organizational leaders may move into government policy and/or regulatory positions relevant to the organizations' goals. Government policy and regulatory leaders may know that lucrative positions in these organizations are available when they leave government. The revolving door is certainly a serious type of conflict of interest, and some deem it corrupt.
Big health care organizations have traditionally been non-partisan. While their leaders certainly may have political views, they used to keep them very quiet. Recently, especially in the US, we have seen evidence that some health care organizations have become partisan, albeit stealthily, throwing their support behind political candidates, parties and organizations that may support their policy and regulatory goals, even while they may also support positions that go against the health care and public health mission, or even may be frankly anti-democratic. In the US, organizations and their leaders now may support partisan aims with dark money, funds whose origin is disguised.
The Transparency International 2018 Corporate Political Engagement Index
A recent report by Transparency International was made public, with little fanfare, in late 2018 that was meant to throw a little light on corporate "engagement" in politics. It included some interesting information on a few multinartional pharmaceutical companies.
The report introduction stated:
For companies, corporate political engagement carries clear risks of bribery and corruption, conflicts of interest and reputational damage. Any interactions with the political process need careful management to avoid falling foul of anti-bribery and corruption legislation. The risks are increased by the fact that companies are vulnerable to mistakes or abuse by employees and third parties acting
on their behalf such as agents, advisers and consultant lobbyists.
Methods
The study on which the report was based concentrated on 104 large corporations that are active in the UK. These included the following large multinational pharmaceutical companies:
The study was based on 20 questions divided in 5 areas.
Three areas were basically about transparency of and accountablity for political activities. These included
- Control Environment, including having transparent policies, methods for ensuring their enforcement, and oversight of same by the board of directors
- Responsible Lobbying, including adequate policies and transparency
- Transparency in Reporting
One was about the Revolving Door, and included whether the company has a "cooling-off period" for people going through the revolving door back to the company. However, it did not directly mention people going directly from leadership positions within the company to government.
One was about Political Contributions, and included whether the company bans them (perhaps the strongest question of the group.)
Each question in each area was scored from 2 for meeting expectations to 0 for failing to do so. Scores were normalized on a scale going from 100 (best) to 0 (worst), and and summarized in "bands" from A (83.3 - 100) down to F (0 - 16.6)
Results
For the three areas regarding transparency and accountablity the results per company were:
Control Environment
- AstraZeneca C
- Eisai C
- GlaxoSmithKline A
- Johnson & Johnson C
- Novartis F
- Pfizer C
- Roche E
- Shire C
Responsible Lobbying
- AstraZeneca E
- Eisai F
- GlaxoSmithKline B
- Johnson & Johnson E
- Novartis E
- Pfizer F
- Roche C
- Shire E
Transparency in Reporting
- AstraZeneca C
- Eisai C
- GlaxoSmithKline A
- Johnson & Johnson C
- Novartis C
- Pfizer C
- Roche C
- Shire C
For the Revolving Door
- AstraZeneca F
- Eisai F
- GlaxoSmithKline A
- Johnson & Johnson F
- Novartis D
- Pfizer F
- Roche E
- Shire F
For Political Contributions
- AstraZeneca F
- Eisai F
- GlaxoSmithKline B
- Johnson & Johnson C
- Novartis F
- Pfizer E
- Roche E
- Shire E
Summary and Discussion
Note that the pharmaceutical companies did not do too badly on the measures of transparency and accountablity, but except for GSK did quite badly on minimizing the revolving door, and again with the partial exception of GSK did very badly on avoiding political contributions.
This suggests that at least some big multinational pharmaceutical corporations that do business in the UK, but also in the US and many other developed countries, have worrisome attitudes towards and likely practices affecting their use of political influence.
The Revolving Door
The majority of companies did not show any real concern about the problem of the revolving door.
In the US, this problem seems to be getting worse. In particular under the Trump regime we see more instances of the incoming revolving door, that is, people moving directly from corporate leadership positions to government policy and regulatory positions in which they could potentially make decisions affecting the corporations from which they came. This is potentially a more serious problem than the outgoing door, yet it was not even discussed in the TI study.
We have repeatedly said, most recently a few days ago, ...
The literature makes clear that the revolving door process is a source of valuable political connections for private firms. But it generates corruption risks and has strong distortionary effects on the economy, especially when this power is concentrated within a few firms.
The ongoing parade of people transiting the revolving door from industry
to the Trump regime once again suggests how the revolving door
may enable certain of those
with private vested interests to have disproportionate influence on how the government works. The country
is increasingly being run by a cozy group of insiders with ties to
both
government and industry. This has been termed crony capitalism. The latest cohort of revolving door transits
suggests that regulatory capture is likely to become much worse in the near future.
Corporate Partisanship, Political Contributions, and Dark Money
Given the increasing evidence that large corporations have become partisan in the US, it is particularly worrisome that at least the pharmaceutical corporations in the TI study have not taken a clear stand against making direct political contributions, or even in favor of making such contributions transparent.
Note that the TI report included the directive "do not make political contributions" among its "principles for responsible political engagement," adding:
Corporate political contributions should not be made on behalf of the company other than in exceptional circumstances where they provide general support for a genuine democratic process, with full transparency and full explanation.
Health care corporations recent and current funding of dark money groups
seems to openly conflict with the corporations' promises of social
responsibility. The slanting of these efforts towards one end of the
political spectrum, one party, and now the current president suggest
that these corporations may have partisan agendas.
Furthermore, the increasing knowledge of these corporate actions raises a big question: cui bono? who benefits?
It is obvious why a pharmaceutical company, for example, might want to defeat legislation that would lower its prices.
It is not obvious why it would want to consistenly support actions by
one party, or by people at one end of the political spectrum, even if
some such people seem "pro-business." After all, for years big
corporations and their executives openly gave money to both US parties
and their candidates, apparently in the belief that this would at least
allow more visibility for the corporations' priorities no matter who was
in power.
Now, the most obvious theory is that the new practice of secret
donations only in right-wing, Republican, and/or pro-Trump directions,
which must be
orchestrated by top corporate management, and which are not disclosed to
employees or smaller corporate shareholders, are likely made to support
the top managers' self interest more than the broad priorities of the
corporations and their various constituencies.
Thus not only is more investigation needed, at the very least, "public"
corporations ought to fully disclose all donations made to outside
groups with political agendas. This should be demanded by at least the
corporations' employees and shareholders, but also by patients, health
care professionals, and the public at large.
Meanwhile we are left with the suspicion that top health care corporate
management is increasingly merging with the current administration in
one giant corporatist entity which is not in the interests of health care, much less government by the people, of the people, and for the people.
Every day seems to bring the latest breathlessly touted innovation in modern health care. The endless hawking of new health care wonders is beginning to inspire some skepticism, but maybe not enough.
The Promotion of Vyvanse for Binge Eating Disorder
For example, at the end of January, 2015, reports of the first ever drug therapy for binge eating disorder appeared. For example, see Jonathan Rockoff writing in the Wall Street Journal
Shire PLC’s drug Vyvanse became the first drug approved for sale in the U.S. to treat some of the estimated 2.8 million adults who have a binge-eating disorder.
Rather ominously, the article described this disorder thus,
Patients regularly eat more food than they need, often when they aren’t hungry and until they feel uncomfortably full, the FDA said. The condition can lead to weight gain, obesity and related health problems.
Furthermore, it appears to be common,
An estimated 2.8 million adults in the U.S. are binge eaters, two times more than those who have the eating disorders anorexia and bulimia combined, according to Shire.
However, now there is a pharmaceutical solution!
In two pivotal studies, binge eating episodes declined to an average of one day a week among patients taking Vyvanse capsules for 12 weeks, down from an average of five days a week, Phil Vickers, Shire’s head of research and development, said in an interview.
'The approval of Vyvanse provides physicians and patients with an effective option to help curb episodes of binge eating,' Mitchell Mathis, director of the FDA’s division of psychiatry drug products, said in a statement.
Because the disease is common, that may mean a lot of money for Shire
For Shire, the approval could eventually add 'several hundred million' dollars in sales, and help the company reach its goal of $10 billion in yearly sales by 2020, said Flemming Ornskov, the company’s chief executive. Vyvanse is the company’s top-selling drug, notching $1.1 billion of the company’s $4.3 billion in total sales during the first nine months of last year.
The only hitch is that all those long suffering victims of binge eating disorder have to be found, and presented with this wonderful new alternative:
One challenge: increasing the numbers of patients diagnosed as binge eaters. Shire estimates that just 3% of Americans with the disease have been diagnosed under the mental-disorder criteria, Dr. Ornskov said.
Brief coverage of the initial approval of Vyvanse appeared in the NY Times. Bloomberg also weighed in, adding to the urgency by underlining how seriously the FDA had handled this:
'Binge eating can cause serious health problems and
difficulties with work, home and social life,' Mitchell Mathis,
director of the Division of Psychiatry Products in the FDA’s
Center for Drug Evaluation and Research, said in a statement.
The FDA gave Vyvanse priority review, a designation for
drugs with promise to 'provide a significant improvement over
available therapies,' the agency said.
Among the major media covering the rollout, only Reuters noted a potential fly in the ointment in this article,
Vyvanse is an amphetamine which, like other
amphetamines, carries the potential for abuse and addiction. They also
have been associated with increase blood press sure and heart rate,
sudden death, stroke, heart attack, insomnia and psychiatric side
effects such as hallucinations and mania.
What Really is the Clinical Evidence Supporting Vyvanse for Binge Eating Disorder?
So Vyvanse is actually lisdexamfetamine, and having been a child when the slogan "speed kills" referred to methamphetamine, not driving automobiles fast, I thought it might be worth looking into the evidence that this somewhat new amphetamine, a relative of that infamous "speed," was now deemed a wondrous treatment for eating too much.
In particular, a recent article in JAMA Psychiatry reported results of one of the two trials Shire did of Vyvanse for binge eating disorder.(1) The study by McElroy et al randomized patients with binge eating disorder to one of four groups, to receive the drug at dosages of 30, 50, or 70 mg/ day or placebo. The investigators followed patients for 11 weeks. The main outcome variable was the number of binge eating days per week reported by the patients.
Patients in all groups were binge eating during approximately 4.5 days/ week at the beginning of the study. At 11 weeks, the average number of binge eating days/ week declined in all groups, dropping 3.3 days/ week for the placebo group, 3.5 for the 30 mg group, 4.1 for the 50 mg group, and 4.1 for the 70 mg group. Thus, by this measure, the difference between patients given placebo versus patients given maximum dosage of the drug was an average decrease of 0.8 binge eating days a week. That does not seem like a very big effect size, or in other words, it seems that the drug had only a small effect on binge eating compared to placebo.
That impression was reinforced by looking at some other study outcomes. The average numbers of binge eating episodes per week at 11 weeks were 1.1 for placebo, 1.2 for the 30 mg group, 0.5 for the 50 mg group, and 0.5 for the 70 mg group. Again, patients given the maximum dose of the drug had only a slightly smaller number of binge eating episodes than those given placebo, reinforcing the impression that the drug is not very effective.
A graph of binge eating days/ week measured over time makes things clearer. It showed that all groups, including patients given placebo, markedly reduced their reported binge eating over the 11 week period. Since the study did not allow any patients to get any other treatment for binge eating other than placebo or the study drug, this again suggests that the drug was not much better than placebo. Further, the apparent reduction in binge eating by patients given placebo suggests a number of possibilities:
- Just paying more attention to patients by putting them in a trial could lead to marked decreases in binge eating, or
- People in binge eating trials could tend to report they are improving, whatever treatment they get, or
- Binge eating may not be a stable phenomenon, and its intensity could vary over time, or
- It may be difficult to make a reliable diagnosis of binge eating disorder.
In summary, at best, the trial showed that Vyvanse only caused small reductions in binge eating, and that binge eating may decrease spontaneously, or at least when patients are given more attention or scrutiny. Thus, even putting the best face on the evidence from a trial done by the maker of Vyvanse does not greatly support the benefits of this drug.
In addition, according to evidence-based medicine advocates, the benefits of a treatment must be balanced with its potential harms. In this study, about 5% of patients given any dosage of Vyvanse had to discontinue its use because of adverse effects. 3/196 patients initially randomized to Vyvanse had serious adverse effects, and one patient died, apparently of an amphetamine overdose. Oddly, the article declared that the one death, due to methamphetamine overdose, was thought by a study investigator not to be related to treatment with another amphetamine, lisdexamfetamine. That makes little sense, given that in a randomized controlled trial, the presumption is that differences in groups given different treatments were caused by these treatments.
In addition, patients given Vyvanse (lisdexamfetamine) had higher rates of various symptoms that are commonly associated with amphetamines, including insomnia, nausea, constipation or diarrhea, anxiety, feeling jittery, palpitations, and sleep disorder.
This suggests that the relatively small apparent benefits of the drug must be weighed against rates of adverse events that are not negligible, especially given the short amounts of time patients were followed. So this study did not show that the benefits of Vyvanse clearly outweigh its harms.
Finally, there were many problems with this trial that further cloud its validity, or applicability to patients (generalizability):
- Patients were diagnosed using DSM-4 criteria, rather than the new DSM-5 criteria
- Patients with any other psychiatric illness were excluded, limiting the applicability of its results.
- Patients with an ostensibly chronic disease were only followed for 11 weeks, so the effects of this drug given for the treatment duration that might be needed to treat a chronic problem are unknown
- The loss to follow-up rate, about 5% for treated patients decreases precision of the results given the relatively small effect size
- The study was done at a large number of sites, initially 32, given the size of the patient population (starting at 260), and one site was dropped because of an "investigation," raising questions about the quality of the study implementation and data collection
So, in my humble opinion, even this Shire sponsored study, which was responsible for half the evidence used to support the approval of Vyvanse for binge eating disorder, provided only weak and questionable evidence that the benefits of the drug outweigh its harms in the short term, and no evidence about long-term use of the drug.
However, no media coverage so far has addressed the weakness of the clinical evidence supporting the use of Vyvanse. I have yet to see any other attempts at a rigorous, skeptical review of the clinical trial evidence supporting Vyvanse in this application. Instead, the media reporting so far seems to have accepted the word of the manufacturer's executives, who obviously have an interest in promoting the drug. (See the WSJ article above which just repeats assertions by a Shire executive.
Why So Much Enthusiasm about a Type of Drug with Such a Bleak Past?
This lack of skepticism was particularly baffling given the nature of the drug that was being promoted, and its long and unfortunate history. As I noted, the amphetamines have proved to be dangerous drugs when abused, and they are abused frequently.
The beginnings of widespread amphetamine abuse grew out of previous efforts to promote these drugs for obesity (which can be, of course, a consequence of eating too much). As documented by Cohen and colleagues(2),
The discovery of amphetamine energized the weight loss industry. Introduced as the Benzedrine inhaler in 1932 by venerable Philadelphia firm Smith, Kline, and French, the American Medical Association (AMA) soon recognized Benzedrine as a treatment of narcolepsy, postencephaletic Parkinsonism, and certain depressive psychopathic conditions. Several clinical studies first published in the late 1930s demonstrated amphetamine’s anorectic effect. The Clark & Clark Company of Camden, NJ, established in 1941, was one of the earliest manufacturers of diet pills combining amphetamine sulfate and thyroid along with phenobarbital, aloin, and atropine sulfate to counteract untoward effects.
These rainbow pills were used with great enthusiasm, however,
adverse events, including deaths, began to be reported to the FDA as early as the 1940s. In the early 1950s, additional adverse reactions including deaths prompted a detailed investigation by the agency.
By the 1960s, the problem was acute,
Efforts had been in place at least since the 1965 Drug Abuse Control Amendments to increase accountability of the use of amphetamine in medical practice. Diversion of the drug for recreational use and the concomitant public health concerns had been recognized as a serious problem by the 1950s, but prescribing amphetamine— whether alone, as part of the rainbow regime, or for indications other than weight loss—continued to rise in the 1960s. Under the Comprehensive Drug Abuse Prevention and Control Act of 1970, which established different schedules for certain drugs based on their medical value vis-รก-vis their abuse potential, amphetamine was relegated to Schedule II. This status mandated even greater hurdles for the prescribing and dispensing of the drug as well as production
ceilings. In the 1970s, FDA also reconsidered obesity as a safe and effective use of amphetamine and its congeners, ruling that amphetamines were effective but only safe for short-term use, which essentially 'marginalized the anorectics and contributed to the eventual decline in their use.'
That is, until they were resurrected as a treatment for attention deficit disorder in children, and then their use was extended to adult patients with so-called adult ADHD, and now to patients with binge eating disorder.
Given this history, the rapid approval of Vyvanse by the FDA, without the benefit of an expert panel, especially given that it was for a supposedly common disorder of adults, is very curious, and worrisome. As Dr Daniel Carlat said (quoted on the WBUR CommonHealth blog),
'I’m concerned that the FDA’s approval of Vyvanse for binge eating
disorder is going to worsen our problems with stimulant abuse,' Carlat
says.
'Vyvanse is a derivative of Dexedrine. We’ve seen epidemics of
Dexedrine abuse in the past when it was used to help people diet. I
predict that the FDA has just opened the gates to another similar
epidemic – after all, binge eating disorder is a subjective diagnosis
that could be potentially expanded to cover many millions of people.'
Why So Much Enthusiasm about Treating Such a Doubtful Diagnosis?
As Dr Carlat noted above, it is not so obvious that binge eating disorder should be considered to be a disease. Starting with first principles, its definition is very vague and subjective. According to the Alliance for Eating Disorders, the DSM-5 criteria for it are:
Recurrent episodes of binge eating. An episode of binge eating is characterized by both of the following:
eating, in a discrete period
of time (for example, within any 2-hour period), an amount of food that
is definitely larger than most people would eat in a similar period of
time under similar circumstances
a sense of lack of
control over eating during the episode (for example, a feeling that one
cannot stop eating or control what or how much one is eating)
The binge-eating episodes are associated with three (or more) of the following:
eating much more rapidly than normal
eating until feeling uncomfortably full
eating large amounts of food when not feeling physically hungry
eating alone because of feeling embarrassed by how much one is eating
feeling disgusted with oneself, depressed, or very guilty afterwards
Marked distress regarding binge eating is present.
The binge eating occurs, on average, at least once a week for three months.
The
binge eating is not associated with the recurrent use of inappropriate
compensatory behavior (for example, purging) and does not occur
exclusively during the course Anorexia Nervosa, Bulimia Nervosa, or
Avoidant/Restrictive Food Intake Disorder.
"An amount of food that is definitely larger than most people would eat in a similar period of time under similar circumstances?" In this case, how are "larger," "most people," and "similar circumstances" defined, and by whom? If I go out to eat with friends, and am the only one who has desert, or soup, for that matter, does that qualify? Similarly subjective are "a sense of lack of control," and "eating more rapidly than normal."
In fact, the DSM-5 which ordained the new binge eating disorder diagnosis has been roundly criticized for embodying "diagnostic hyperinflation," turning aspects of the human condition, symptoms, and behavioral variants into disease. Dr Allen Frances, who has been one of its prime critics, described "binge eating disorder" thus,
Excessive eating 12 times in 3 months is no longer just a manifestation
of gluttony and the easy availability of really great tasting food.
DSM-5 has instead turned it into a psychiatric illness called Binge
Eating Disorder.
Perhaps the enthusiasm to make binge eating disorder a disease had to do more with the financial relationships among the authors of DSM-5 and pharmaceutical companies that wanted to market drugs for the problem. An article by Cosgrove and colleagues(3) noted that members of the DSM-5 work group that approved binge eating disorder as a disease included three people with financial relationships with Eli Lilly, maker of Cymbalta, three people with relationships with GlaxoSmithKline, maker of Lamictal, and one person with a relationship to Shire, maker of Vyvanse.
Yet the discussion of Vyvanse in the big media outlets did not address these past questions about the validity of the binge eating diagnosis for which it is now being promoted.
The Over-Marketing of Binge Eating Disorder to Promote Vyvanse
This week, however, at least some skepticism about other aspects of Vyvanse's promotion appeared in a major media outlet. Just a few weeks after that initial coverage, the NY Times published
a somewhat more skeptical take on the promotion of Vyvanse. It noted
that Shire was underwriting celebrity endorsements without disclosing
its financial backing of them,
The retired tennis
player Monica Seles spent this month making the rounds of television
talk shows, appearing on everything from 'Good Morning America' to 'The
Dr. Oz Show' to share her personal struggle with binge eating.
'It
took a while until I felt comfortable talking about it,' she said in a
People magazine interview, explaining that she secretly devoured food
for years while she was a professional athlete. 'That’s one of the
reasons I decided to do this campaign: to raise awareness that binge
eating is a real medical condition.'
But that is not
the only reason. Ms. Seles is a paid spokeswoman for Shire, which late
last month won approval to market its top-selling drug, Vyvanse, to
treat binge-eating disorder,...
Shire also was funding patient groups as part of its promotional efforts,
And
patient advocacy groups — freshly infused with donations from Shire —
began driving social media traffic to a company website that provides
advice on how to raise the issue of binge eating with a doctor.
Furthermore,
Shire has been trying to raise awareness of the new binge eating
disorder diagnosis in ways that obfuscate its promotional interests,
Shire
appeared to be following a familiar drug industry playbook by promoting
awareness of a disorder, in this case binge eating, before more
directly marketing its treatment. A company website,
BingeEatingDisorder.com, makes no mention of Vyvanse but provides
detailed information about how to talk about the disorder with a doctor,
including a printable symptom checklist and sample opening lines to
start the conversation. The site also tells patients 'don’t give up' if a
doctor initially resists.
Some experts in
prescription-drug abuse said the content was troubling because it
appeared to coach patients about how to receive a diagnosis for a
relatively uncommon condition, or shop for a new doctor if they were not
successful.
Note Shire's use of undisclosed payments to celebrity spokespeople and patient advocacy groups and a disease awareness website whose connection to the company's drug was obscured suggests the operation of a stealth marketing campaign. Furthermore, the article noted that Shire has been accused of deceptive marketing in the past, and specifically for its marketing of Vyvanse and another stimulant.
In 2011, the F.D.A. cited Shire, which is based in Dublin, for misleading advertising, and last fall the company paid $56.5 million
to settle federal charges that it improperly promoted Vyvanse, Adderall
and other drugs. Among the allegations, which Shire denied, was that
the company played down Vyvanse’s addiction potential and said it would
prevent car accidents, divorce, arrests and unemployment.
The article also emphasized concerns about this new pushing of amphetamines,
With the approval of Vyvanse for binge eating, 'now we have another
reason for the public to learn about the glories of amphetamine — it’s
very worrisome,' said Dr. Lawrence H. Diller, a behavioral pediatrician
in Walnut Creek, Calif., who has written about A.D.H.D. drugs. 'My hat’s off to Shire. They’ve done it again.'
Also,
Several
drug safety and addiction experts said the approval was of particular
concern because of amphetamines’ troubled history as a treatment for
weight loss. Vyvanse is converted by the body into an amphetamine when
it is swallowed.
From the 1940s through the 1970s,
the drugs were commonly prescribed to overweight people who then became
addicted. After public outcry and tighter government controls,
companies stopped selling amphetamines as obesity treatments and their
use is now tightly restricted. In 2012, the F.D.A. approved Qsymia,
a drug combination that treats obesity and contains the amphetamine
phentermine, although unlike Vyvanse, it is classified by the federal
government as having a low potential for abuse.
The
F.D.A. expressly forbade Shire from promoting Vyvanse as an obesity
drug, but some drug safety experts said they worried its weight-loss
attributes could be attractive to people who habitually overeat. The
company says about 80 percent of people with the disorder are overweight
or obese. Weight loss and appetite suppression are a common side effect
of amphetamines.
'There’s
so many reasons to be concerned about this,' said Dr. Andrew Kolodny,
the chief medical officer of Phoenix House, a drug treatment
organization.
He
questioned why the F.D.A. approved the new use of Vyvanse so swiftly
and said that given amphetamines’ troubled past, more caution was
necessary. 'We had a horrible experience with amphetamines in this
country, so the fact that this would just get rushed through without
even bringing it before an advisory committee is especially concerning,'
he said.
However, the NY Times article still did not address the lack of good evidence that the drug provided a substantial benefit even in terms of just reducing binge eating, and questions raised whether binge eating disorder is a valid diagnosis.
Summary
Once again we see the overenthusiastic promotion of the latest wonder drug, starting with uncritical media reports that parroted drug company executives. At least this time some skepticism appeared about how an apparent stealth marketing campaign was organized, and about how the drug's riskiness was soft-pedaled.
However, so far there has been little skepticism about the efficacy of the drug. In fact, close reading of the report of one major trial showed that at best it has minimal efficacy, and even the evidence for that is weak and sketchy. Furthermore, major news media have been hesitant to cite the real questions that have been raised about the nature of the disease for which the drug was advocated.
Most concerning is that this promotion was of an amphetamine, a type of drug with a very dark past, a type of "hard drug" responsible for major abuse problems, and known to cause particularly bad side effects, a type of drug whose illicit use has been previously sparked by over-enthusiastic marketing for dubious indications.
So once again I get to say that physicians need to be much more skeptical about the new "innovations," often promoted as miracle cures, that seem to appear weekly. Attempts to educate physicians about clinical epidemiology, the principles of evidence based medicine, and just simply how to read a clinical research article with an appropriately skeptical and critical eye seem to have fallen by the wayside. Furthermore, the diminishing number of health care journalists with diminishing resources may not be able to sufficiently skeptical of the marketing and public relations hype surrounding new drugs and devices. Physicians and journalists need to have the courage to be more skeptical, and the public, who may trust journalists and physicians to cut through the bloviation, need to advocate for better training of physicians and journalists.
Finally, health care professionals and the public at large have been told to trust government regulators to only approve medicines that are safe and effective. Yet the US Food and Drug Administration increasingly seems too cowed to challenge the pharmaceutical industry, and did not seem to exert much critical thinking before approving an amphetamine for over-eating. The public and health care professionals ought to be advocating intensely for regulators that are less captured by the industry they are supposed to oversee.
As we have said until blue in the face, true health care reform would
bring some skeptical thinking and regard for evidence and logic into the
health policy discussion.
For our closing musical inspiration, or warning, note the chorus in "Amphetamine Annie" by Canned Heat...
"Speed Kills"
References
1. McElroy SL, Hudson JI, Mitchell JE et al. Efficacy and safety of lisdesamfetamine for treatment of adults with moderate to severe binge eating disoder: a randomized clinical trial. JAMA Psychiatry 2015; Link here.
2. Cohen PA, Goday A, Swann JP. The return of rainbow diet pills. Am J Pub Health 2012; 102: 1676-1686. Link here.
3. Cosgrove L, Krimsky S, Wheeler EE et al. Tripartite conflicts of interest and high stakes patent extensions in the DSM-5. Psychother Psychosom 2014; 83: 106-113. Link here.
Here we go again. A big drug company has settled claims of deceptive marketing, yet no individual was held accountable. The most extensive coverage came from the Philadelphia Inquirer, presumably since the announcement came from the local US Attorney.
The basics were:
Shire Pharmaceuticals L.L.C. will pay
$56.5 million to settle allegations that it inappropriately promoted the
sale of ADHD medicine, among other drugs, the U.S. Attorney's Office in
Philadelphia said Wednesday.
Shire is registered in the Channel Islands and headquartered in Dublin, but operates from the United States....
As is usual in such cases,
Shire admitted no wrongdoing, but also
entered into a five-year Corporate Integrity Agreement with the Office
of Inspector General for the Department of Health and Human Services.
The detailed allegations make for interesting reading.
The settlement resolves allegations
that, between January 2004 and December 2007, Shire promoted Adderall XR
for certain uses despite a lack of clinical data to support such claims
and overstated the efficacy of Adderall XR, particularly relative to
other ADHD drugs. Among the unsupported claims allegedly made by Shire
was that Adderall XR was clinically superior to other ADHD drugs because
it would 'normalize' its recipients, rendering them indistinguishable
from their non-ADHD peers. Shire allegedly stated that its competitors’
products could not achieve similar results, which the Justice
Department contended was not shown in the clinical data Shire collected.
Shire also marketed Adderall XR based on claims that Adderall XR would
prevent poor academic performance, loss of employment, criminal
behavior, traffic accidents, and sexually transmitted disease. In
addition, Shire promoted Adderall XR for the treatment of conduct
disorder, an indication not approved by the Food and Drug Administration
(FDA).
The settlement further resolves allegations that, between February
2007 and September 2010, Shire sales representatives and other agents
also allegedly made false and misleading statements about the efficacy
and abuse liability of Vyvanse to state Medicaid formulary committees
and to individual physicians. For example, one Shire medical science
liaison allegedly told a state formulary board that Vyvanse 'provides
less abuse liability' than 'every other long-acting release mechanism'
on the market. No study Shire conducted concluded that Vyvanse was not
abusable, and, as an amphetamine product, the Vyvanse label included an
FDA-mandated black box warning for its potential for misuse and abuse.
Shire also made unsupported claims that treatment with Vyvanse would
prevent car accidents, divorce, being arrested, and unemployment.
Additionally, the settlement resolves allegations that, from April
2006 to September 2010, Shire representatives improperly marketed
Daytrana, administered through a patch, as less abusable than
traditional, pill-based medications. The settlement also resolves
allegations that, for part of the foregoing periods, Shire
representatives improperly made phone calls and drafted letters to state
Medicaid authorities to assist physicians with the prior authorization
process for prescriptions to induce these physicians to prescribe
Daytrana and Vyvanse.
Finally, the settlement resolves allegations that, between January
2006 and June 2010, Shire sales representatives promoted Lialda and
Pentasa for off-label uses not approved by the FDA and not covered by
federal healthcare programs. Specifically, the government alleged that
Shire promoted Lialda off-label for the prevention of colorectal cancer.
Thus, the allegations were that Shire marketers and "agents" made false, sometimes apparently ridiculous claims about four different medicines. Some of these claims, for example, that an amphetamine drug had no abuse potential, or that an anti-inflammatory drug would prevent cancer (in patients at risk for cancer), could conceivably have led to patients being harmed.
The pact resolves one outstanding issue ahead of Shire's planned $54 billion acquisition by AbbVie Inc.
So note that the dollar amount of the settlement is approximately one one-thousandth (0.1%) of the total value of Shire.
According to the Philadelphia Inquirer, no one admitted guilt, and no individual will pay any penalty:
'We are pleased to have reached a
resolution and to put this matter behind us,' Flemming Ornskov, Shire’s
chief executive officer said in a statement.
So this follows the usual formula for legal settlements in health care. A big pharmaceutical company was alleged to have deceptively marketed multiple products. Some of the deceptions could have lead to patient harm. The government took the company to court, but the end result was a monetary penalty paid by the company that might appear large, but which was tiny compared to the assets of the company. The company did not have to admit guilt. No individual at the company paid any penalty or suffered any consequence. While the organization had to sign a "corporate integrity agreement," it is not clear that such agreements prevent future bad behavior.
There have been many, many such settlements, as we have discussed on Health Care Renewal. At least these settlements serve as evidence that many, many large health care organizations have behaved unethically, often in ways that not only increase health costs, but may directly harm patients. Yet the settlements seem bent over backwards not to trouble the people who personally profited from unethical behavior.
Individual company marketers, their supervisors, and top executive likely made more money because of the revenue brought in by the unethical practices. However, the settlement somehow avoided identifying any of them, or even stating unequivocally that the company, or any of its employees did anything wrong. That is absurd, since if nothing bad was done by anybody, why did the company have to pay anything? Beyond that, if individuals who work for big drug companies, and other large health care organizations know that whatever they do in their official capacities, they will not be held personally responsible, what would deter them from taking unethical actions in the future?
Most citizens trust drug companies to provide safe effective medicines. Marketing drugs as safer than they are, or for purposes for which they are not effective abuses the companies' entrusted power. Doing so in order to enrich oneself thus is a manifestation of corruption. The ongoing parade of legal settlements is thus a marker of how corrupt health care has become.
Furthermore, the continued inability of regulators and law enforcement to do more in the face of corruption suggest moral failure, incompetence, and perhaps more corruption.
We will never achieve true health care reform, and will never really improve our vastly over-priced, ineffective health care system until we address this sort of health care corruption.
A final note: Eric Holder, the current US Attorney General, will soon leave. While he has been hailed for promoting human rights in some instance (that is, for LGBT individuals), he has been criticized for never making an effort to pursue the top corporate executives who were responsible for the global financial collapse of 2008 (look here) although the Department of Justice constantly goes after relatively small scale white collar criminals. He also appears to have almost never pursued any top corporate executives involved in deceptive, unethical, illegal or corrupt health care practices, while the government constantly pursues perpetrators of relatively small scale Medicare and Medicaid fraud (look here). One of his US Attorneys notably pursued the late Aaron Swartz for vaguely specified computer crimes which did not appear to harm anyone while she gave passes to executives at big health care corporations that settled cases of alleged actions that likely harmed patients (look here). His failure to pursue such large scale health care corruption should be regarded as no less serious than his failure to pursue financial corruption.
It was a busy week in court for some US health care organizations.
Just before the US Independence Day holiday, news reports indicated that a jury in Alabama found that two large pharmaceutical firms, GlaxoSmithKline and Novartis, had defrauded the state. For example, per the Associated Press,
A state court jury on Tuesday found two major pharmaceutical companies defrauded Alabama in a long-running Medicaid drug pricing scheme and ordered the firms to pay more than $114 million in damages.
The jury found that GlaxoSmithKline should pay the state $80.8 million in compensatory damages and that Novartis should pay about $33.7 million in similar damages.
The state claimed the two companies charged the Medicaid program one price for drugs while offering discounts and special prices to other companies.
The companies had denied any fraud, contending they followed proper procedures in setting drug prices.
This week, St Louis University settled a law-suit by a whistle-blower who charged the university had defrauded the federal government by overcharging for public health research grants. Per the Associated Press, via the Kansas City Star,
St. Louis University has agreed to pay $1 million to resolve a whistleblower lawsuit claiming its School of Public Health tried to defraud the government, officials said Tuesday.
The lawsuit claimed the school overstated faculty time spent on projects involving federal grants.
The government will dismiss the lawsuit and the university will be subject to increased scrutiny in annual audits of federally funded research, U.S. Attorney David Nahmias said.
Nahmias said Andrew Balas, former dean of the School of Public Health, will receive $190,000 of the settlement for his role.
Balas alleged in the initial lawsuit in May 2005 that supplemental income of certain faculty members was inflated by claims of time they spent on grants received from the U.S. Centers for Disease Control and Prevention in Atlanta.
An investigation revealed that grants from the National Institutes of Health and the Department of Housing and Urban Development also were involved, with similar inflation of hours worked, Nahmias said.
University spokesman Clayton Berry issued a news release denying that the school schemed to defraud the government but said it agreed to settle to avoid legal costs.
Balas first tried to stop the improper billings within the university but was forced to resign for refusing to go along with them, said his attorney, Michael Sullivan.
Sullivan said the university’s evaluation of Balas’ performance as dean was '100 percent positive' in 2003, one year after he was lured from another school.
'Only weeks later, after protests from university employees who were profiting from the unlawful payments and wanted more, the university made sure Dean Balas knew that he was no longer welcome,' Sullivan said.
Finally, the former CEO of Transkaryotic Therapies, a biotechnology company, settled a lawsuit by the US Securities and Exchange Commission (SEC) that claimed he misled investors. Per the Boston Globe,
A former Transkaryotic Therapies Inc. executive agreed to pay more than $1.1 million to settle claims that he misled investors about problems facing the Cambridge biotech company's flagship drug, the government said yesterday.
The Securities and Exchange Commission accused former Transkaryotic chief executive Richard F. Selden, 49, of inflating the company's stock by making optimistic statements about the drug Replagal, which was intended to treat a rare disorder called Fabry's disease, while hiding the fact it failed a key clinical trial and that he knew federal regulators were likely to reject the company's application to market the drug. The SEC said the Food and Drug Administration told the company on several occasions that it needed further trials to win approval, something the company didn't tell investors before Selden sold 90,000 shares of company stock.
Ultimately, Transkaryotic's drug stumbled in the United States, and Selden was fired in February of 2003. British drug maker Shire PLC bought the company, known as TKT, for $1.6 billion in 2005....
The SEC sued Selden three years ago, accusing him of pocketing $1.6 million in illicit profits from selling the stock before telling investors the company's experimental drug was in trouble.
To settle the suit, Selden agreed to pay a penalty of $125,000 and give up $714,800 in profits from selling 90,000 shares of stock, plus $326,617 in interest.
Even I am sometimes amazed at the frequency of legal judgments and settlements involving accusations of fraud, or other dishonest or deceptive behavior by the leadership of health care organizations. Here were three, involving two pharmaceutical companies, a major university and school of public health, and a biotechnology company announced in the last 9 days. This indicates the pervasiveness of sleazy behavior amongst the leadership of all kinds of health care organizations.
It appears to me that there are more such judgments and settlements occurring that involve health care organization than involve other kinds of organizations and companies, although I have never seen any systematic data about this. This is particularly disturbing since one would expect that health care leadership ought to be held to a higher standard, than say the leaders of trash-hauling firms and used car dealerships.
Like global warming, the erosion of professional values and medical education by commerce shows no sign of slowing. The latest scandals involve Medscape. Medscape is a medical communications company that produces and distributes CME programs and other quasi-educational offerings, such as “Expert Interviews” and News items. A subsidiary of WebMD, Medscape is accredited by ACCME, and it relies on drug company money for its production costs. Medscape also displays multiple advertisements on every web page. Medscape uses salaried and contract medical writers to produce the “educational material.” The content is pedestrian, mainly because it makes no pretense of really educating – it is primarily a vehicle for promoting the sponsors’ products with varying degrees of slyness and subtlety, as Daniel Carlat has documented here http://carlatpsychiatry.blogspot.com/2008/06/medscapes-cme-corruption.html#links Some items are academic wallpaper, non-promotional pieces designed to create an appearance of commitment to education. For most featured items, Key Opinion Leaders (KOLs) are hired to push the material. These KOLs are paid for their roles, although Medscape never says so, much less discloses how much it pays. If they wish to be engaged regularly, the KOLs know they need to stay “on message.” These are standard arrangements in today’s amoral world of CME. Daniel Carlat recently published a fine exposรฉ of Medscape’s corruption of CME standards (link above).
An especially distasteful practice is Medscape’s use of the names, reputations, and credibility of major professional societies to give its indifferent CME offerings and infomercials more pizzaz. Just to give two examples, Medscape web pages are currently hijacking the public images of both the American Psychiatric Association (APA) and the American College of Neuropsychopharmacology (ACNP), featuring highlights of these organizations’ annual meetings as CME and other items. These “highlights” from the APA and ACNP meetings are offered by Medscape FOR CME CREDIT!!! For us to call this presumptuous would be an understatement. For Medscape to dress it up with sanctimonious statements about avoiding conflict of interest is insufferable.
Both APA and ACNP annual meetings are closed events, so how does a commercial CME outfit like Medscape get its hands on these restricted materials? The most likely explanation is that venal KOLs accept Medscape payments for producing puff pieces with the organizational tagline (highlights of the APA/ACNP meeting!). In effect, these KOLs trade on their membership in professional organizations for personal gain in return for “authoring” Medscape-produced CME items, “Expert Interviews” and News pieces. How tacky is that? The KOLs who “authored” mini-manuscripts or provided “Expert Interviews” for Medscape’s “highlights” of the 2007 ACNP annual meeting, whether as infomercials or wallpaper, should know better. You can find them here and in the associated links: http://www.medscape.com/viewprogram/8683
Medscape is paid by Pharma to produce these items. The APA 2008 annual meeting highlights on Medscape’s website were supported by an “independent educational grant” from Shire and by an “unrestricted educational grant” from Bristol-Myers Squibb Company/Otsuka America Pharmaceuticals, Inc. It is a good bet that Medscape shares none of that revenue with the APA. Likewise, the ACNP 2007 annual meeting “highlights” were supported by an “independent educational grant” from Vanda Pharmaceuticals. We can be sure ACNP saw none of that revenue.
So what we have is Medscape profiting from Pharma sponsors while juicing up their mediocre CME offerings with tag lines to “highlights” of the APA and ACNP annual meetings. How tacky can you get? How tacky? This tacky: Here is the disclaimer published by Medscape’s lawyers regarding the ACNP meeting.
An additional disclaimer states, “This activity is not sanctioned by, nor a part of, the American College of Neuropsychopharmacology.” Well, fine. If it wasn’t sanctioned, why is Medscape splashing it over its web pages? I am confident ACNP gave Medscape no such authorization.
One hopes that APA and ACNP will publicly disown this corrupt use of their names and reputations for commerce by Medscape. The situation with APA is problematic because the incoming APA president, Alan Schatzberg, has been a frequent “Expert Interviewee” on Medscape. It remains to be seen whether his compromise and conflict will affect the organization’s response.
So, nobody at Medscape is accountable for the bias and bs in these items, even though they were written by Medscape staff and contractors. Medscape’s disclaimer tells us to go after the “independent authors.” That’s exactly what I intend to do in my next posting. Meanwhile, if Medscape wants credibility it will need to clean up its act. A good place to start would be to stop using these compromised KOLs who push infomercials and who provide soothing wallpaper. The real solution would be for Medscape to stop its skimming and money laundering activities altogether. Perhaps that is hoping for too much. Or they could just run naked advertising and they won’t need to bother with ACCME requirements. On the other hand, self-respecting health care professionals can just say no to Medscape’s kind of crap.
And what exactly does an “independent educational grant” mean, anyway? We will examine that trope in my next posting, which features the poster boy for compromised KOLs in psychiatry, Charles Nemeroff, MD from Emory University’s department of psychiatry. In that example, Medscape joins forces with Nemeroff to promote an entirely new level of sleaze. Stay tuned.
