Mass-medication 2: the prevention element – a potential revenue stream?

As Andrew Miles, senior UK vice-president of GlaxoSmithKline observed cryptically in the Financial Times recently, “As much as people might think that the prevention element may not be a revenue stream for the company, it provides phenomenal insights.”

In July, the journal Science Translational Medicine published a report of the trial at Novartis Institutes for Biomedical Research in Massachusetts into a treatment, administered as two daily pills. A Times article noted that it was found to cut the number of infections in older people. Stephen Evans, the professor of pharmacoepidemiology at the London School of Hygiene and Tropical Medicine, said that the study was only an incremental improvement on the treatments already available and there are unanswered questions about the possible side-effects of the drugs.

Mass medication is an iatrogenic catastrophe

In June, this view was expressed in a BMJ article by James Le Fanu, retired GP and journalist. He wrote that ‘profligate’ prescribing has brought a hidden epidemic of side effects and no benefit to most individuals. There is no drug or procedure with its “chance of good” that may not harm some. The more doctors do, the greater that risk. Over the past 20 years there has been:

• a dizzying fourfold rise in prescriptions for diabetes treatments,
• sevenfold for antihypertensives,
• and 20-fold for the cholesterol lowering statins.
• Meanwhile the number of people taking five or more different drugs has quadrupled to include almost half of those aged 65 or over.

He continues: “The consequences of this massive upswing in prescribing? A hidden epidemic of immiserating symptoms such as fatigue, muscular aches and pains, insomnia, and general decrepitude, a 75% rise in emergency admissions to hospital for adverse drug reactions (an additional 30 000 a year) …

Proposals have been made in the past for mass or even universal medication by aspirin and statins

The NHS now concludes that the risk of side effects (particularly the risk of bleeding) outweighs the benefit of preventing blood clots. It has long been known that the pills carry a risk of gastro-intestinal bleeding. But a new University of Oxford study, published in The Lancet, suggests that the danger increases far more sharply with age than was thought, according to Professor Peter Rothwell, lead author. A Telegraph artlcle reports on his 2017 findings, adding that taking a daily aspirin is more dangerous than was thought, causing more than 3,000 deaths a year.

Britain is already the “statins capital” of Europe

The UK has the second highest prescribing levels in the Western world, with aggressive prescribing of the medication by GPs, whose pay is linked to take-up of the pills.

In 2014 it was reported that twelve million people (one in four adults) would be told to take statins under controversial new NHS guidelines. Draft proposals from health watchdogs were that the vast majority of men aged over 50 and most women over the age of 60 are likely to be advised to take the drugs to guard against strokes and heart disease. The National Institute for Health and Care Excellence (Nice) had cut the “risk threshold” for such drugs in half and experts said that the number of patients advised to take the drugs is likely to rise from seven million to 12 million.

And current medical guidance says that anyone with a 20% risk of developing cardiovascular disease within 10 years should be offered statins.

Almost all men over 60 and all women over 75 in England qualify for statin prescriptions under guidelines adopted by the National Institute for Health and Care Excellence in 2014, a 2017analysis shows – see BMJ.

However, some health experts have questioned the industry forces behind these studies. The first recommendation was put out in 2013 by the American College of Cardiology (ACC) and the American Heart Association (AHA).  CNN reports that a number of experts who worked on the ACC/AHA guidelines had financial links to drug companies, which they disclosed publicly. No conflicts of interests were reported by the authors of the United States Preventive Services Task Force guidelines, but nearly all of the trials they included in their analysis were sponsored by industry, according to Dr Rita Redberg, who stressed this point in a January 2017 editorial in the journal she oversees. “The ACC did not follow its own conflict of interest guidelines“..

Fluoridation – or any practice that uses the public water supply as a vehicle to deliver medicine – violates medical ethics in several important ways:

• It deprives the individual of his or her right to informed consent to medication.
• It is approved and delivered by people without medical qualifications.
• It is delivered to everyone regardless of age, health or nutritional status, without individual oversight by a doctor and without control of dose.
• The safety of fluoridated water has never been demonstrated by randomized controlled trials–the gold standard study now generally required before a drug can enter the market.

Fluoridating water is a form of mass medication and most western European nations have rejected the practice — because, in their view, the public water supply is not an appropriate place to be adding drugs.

Who profits from all these instances of largescale medication?

 

 

 

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A pharmaceuticals market of 800,000 – and growing

“Drug companies got out of antibiotics as their attention switched to much more lucrative daily medicines for chronic diseases”

In March, at the World Health Organisation’s first Ministerial Conference on Global Action Against Dementia in Geneva, Jeremy Hunt, the UK’s health secretary, announced plans to boost early-stage research into Alzheimer’s disease and other forms of dementia in order to find an effective treatment. Just three new drugs for the condition have reached market in the past 15 years and these only alleviate symptoms.

The WHO conference was supported by the Department of Health of the United Kingdom of Great Britain and Northern Ireland, and the Organization for Economic Cooperation and Development (OECD). Both days were webcast.

Ongoing lifelong drug treatment is very profitable – not so pre-emption

The $100m venture capital fund will be backed by the UK government and several of the world’s biggest pharmaceuticals companies, amongst them US investment bank JPMorgan, GlaxoSmithKline, Johnson & Johnson, Pfizer, Eli Lilly and Biogen.

Drug companies had lost billions of dollars in many failed trials and Patrick Vallance, president of research and development at GlaxoSmithKline, said the venture fund was a good way to spread risk and share expertise.

He added that there are rewarding economic incentives for research. “Nobody doubts that if you find an effective medicine for dementia it will be very profitable.”

True – and discovering and addressing the causes would remove this market opportunity.

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Today’s broadcast theme:

Infectious bacteria are becoming resistant to the drugs that used to kill them. The last new class of antibiotics was discovered in the 1980s. There is little in the development pipelines of the world’s pharmaceutical industry. Drug companies got out of antibiotics as their attention switched to much more lucrative daily medicines for chronic diseases. Public funding on antibiotic research has also withered.

Does Big Pharma put profits before public health? EP to legislate

 A recent report by the Cochrane Collaboration, an independent research network, found no evidence that Roche’s costly Tamiflu antiviral medicine reduced risk of hospitalisation or death from influenza. Tom Jefferson, clinical epidemiologist and co-author of the Cochrane review, said “only the tip of the iceberg” of the evidence was made available to regulators when the drug was approved.

Stocks of antiviral treatment Tamiflu housed in a UK warehouse (picture from French website)

Fiona Godlee, editor-in-chief of the BMJ, which published the report, says the case highlights the “irredeemable conflict of interest” between the need for impartial trial data and the industry’s commercial interests. “We have evidence time and time again that they overestimate the benefits [of new drugs] and underestimate the harm.”

Andrew Ward, in the Financial Times, reports that Roche had long resisted demands from scientists to open its trial data to scrutiny but relented last year. Disputed clinical data was at the heart of controversy over Tamiflu, disclosing questionable efficacy rather than health risks.

In response to such criticism, drugmakers, including Roche, GSK and Johnson & Johnson, have announced steps over the past year to open their clinical trial data to independent scrutiny. Others cite the need to protect intellectual property and patient confidentiality. However, the European parliament has already passed draft legislation requiring detailed summaries of all trial data to be made public.

Other fairly recent cases:

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• $250m verdict against Merck & Co on behalf of a widow who blamed her husband’s fatal heart attack on its Vioxx painkiller;

• $3bn US fine paid by GlaxoSmithKline for marketing abuses in 2012;

• a bribery probe against GSK in Iraq;

• and a French competition inquiry into whether Roche and Novartis colluded to block a cheaper alternative to their blockbuster Lucentis eye treatment.

Ward concludes: “All of them, in one way or another, support the claims of industry critics who say big pharma puts profits before public health – from cherry-picking clinical trial data to conceal health risks to bribing doctors and blocking cheaper medicines”

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Big pharma: prosecutions for discounting, bribery and ‘education’

Today, Euronews reports from Croatia that pharmaceutical company Farmal, and 364 individuals, have been charged with bribery and abuse of office. Farmal allegedly ran a network of doctors, giving them gifts in return for prescribing the company’s products

Only two days ago Andrew Jack reported that US fines from whistleblower and government prosecutions against the pharmaceutical industry reached $20bn in the period 1991-2010. In less than three years since then, companies have been given further penalties totalling more than $13bn.

Jack cited four examples:

• Last year, Eli Lilly paid $29m to the US Securities and Exchange Commission after evidence showing it offered discounts to fund bribes to win business in Brazil and Kazakhstan.

• Pfizer was fined $60m for activities including “incentive trips” to Greece for Bulgarian doctors who agreed to meet prescription targets for its drugs.

• Johnson & Johnson  channelled more than $100,000 through a subsidiary company to a sympathetic nurse in order to boost prescriptions of Natrecor, a heart medicine; she spoke favourably about the drug in talks, trained colleagues in its use and put her name on an article in a medical journal to boost sales. J&J paid a $2.2bn fine in November for practices stretching back over a decade – the latest in an escalating series of penalties against the pharmaceutical industry for the way it markets its products.

• In China, GlaxoSmithKline has been accused of paying up to $500m in bribes to local doctors.

He points out that the marketing process begins before new drugs are approved by regulators. There has been growing concern in recent years that articles in influential medical journals describing experimental products, assessed by reviewers and editors, are excessively favourable to new drugs. On occasion there has been selective design and presentation of the evidence and publication of ‘flattering’ safety data.

Building relationships with prescribers

• Sales representatives make presentations to doctors; a study last summer showed that, on average, US doctors who received payments from companies were twice as likely as their peers to prescribe their products.

• Money is spent on bringing doctors to conferences for “continuing medical education”, often in luxury international hotels. GSK last year settled a record $3bn fine in the US for paying prescribers to attend conferences in luxury resorts in Hawaii.

• “Key opinion leaders” among physicians are paid as consultants to give speeches and presentations to their peers. They often sit on professional bodies that draft treatment guidelines. They may also be paid to advise on and recruit patients into lightly regulated “post-marketing” trials for drugs that are already approved.

• Companies have also offered doctors discounts or donations of their medicines to wean them off rival products.

Examples of improved practice

US and European regulators are pushing for greater publication of clinical trial data, opening the possibility of third-party analysis of drug safety and efficacy.

Doctors and healthcare systems are being advised to pay for continuing medical education, reducing the influence of industry funding.

Some universities and hospitals already ban visits by sales representatives or consulting payments to doctors.

AstraZeneca no longer pays for physicians to attend international medical conferences. GSK last week announced similar moves, as well as plans to sever any bonuses to its marketing staff linked to individual sales targets. It wants them to be judged by the quality of medical advice they provide doctors rather than the crude volume of prescriptions.

“Health technology assessment”, the use of third-party review of the evidence of the value of treatments to guide doctors’ prescribing habits is being undertaken by the National Institute for Health and Care Excellence (NICE) in the UK; the transparency commission in France and Amnog in Germany already conduct such assessments of new medicines.

Legal advice: “Over 12 months after the UK Bribery Act was introduced, and with increasing enforcement in the pharmaceutical and medical business sectors, pharmaceutical companies should ensure that their compliance programmes are in place and updated to reflect developments over the last 12 months”.

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Whistleblowers in the Orphan Medical/Jazz Pharmaceuticals settlement and cases that were part of the settlements by Amgen, Glaxo and Pfizer: http://www.forbes.com/sites/erikakelton/2013/01/04/off-label-pharma-prosecutions-wont-be-silenced-by-first-amendment-decision/

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Johnson & Johnson, who “recklessly put at risk” the health of children & dementia patients, ordered to pay $2.2 billion

Subhash Sule of India’s CHS-Sachetan draws our attention to the resolution of the case against Johnson & Johnson

An Arkansas judge ordered J&J and subsidiary Janssen Pharmaceutical to pay $2.2 billion to end civil and criminal investigations. They were alleged to have paid  ‘kickbacks’ and fraudulently marketed pharmaceuticals for off-label uses. The case concerned anti-psychotic drugs Risperdal and Invega and the heart drug Natrecor:

• 1999 – 2005, J&J and its subsidiary Janssen Pharmaceuticals Inc promoted Risperdal for unapproved uses, including controlling aggression and anxiety in elderly dementia patients and treating behavioral disturbances in children and in individuals with disabilities, according to the complaint.

• Janssen’s sales representatives “aggressively” promoted Risperdal through a special “ElderCare sales force” targetting nursing home operators.

• The company paid millions of dollars in kickbacks to Omnicare Inc, the nation’s largest pharmacy specializing in dispensing drugs to nursing home patients, under various guises including “educational funding.

• In a separate civil complaint, the government alleged that J&J and its subsidiary Scios promoted its heart failure drug Natrecor as a weekly treatment for patients, despite no scientific evidence to support this approach.

U.S. Attorney General Eric Holder said that Johnson & Johnson’s conduct “recklessly put at risk” the health of children, dementia patients and others to whom the drug was prescribed at a time it was only approved by the U.S. Food and Drug Administration to treat schizophrenia adding:

“Through these alleged actions, these companies lined their pockets at the expense of American taxpayers, patients and the private insurance industry”.

Drug manufacturers have paid fines over the past decade for alleged improper marketing of several medicines.  Pfizer Inc in 2010 agreed to pay $2.3 billion to settle allegations it improperly marketed 13 drugs, including kickbacks to healthcare providers. Last year, GlaxoSmithKline Plc agreed to pay $3 billion to resolve criminal charges that it improperly targeted its Paxil depression treatment to children, sold its Wellbutrin antidepressant for unapproved uses and failed to inform U.S. regulators of safety risks seen with its Avandia diabetes drug.

Sources:

http://www.huffingtonpost.com/2013/11/04/johnson-and-johnson-drug-marketing-charges_n_4212858.html

http://www.reuters.com/article/2013/11/04/us-jnj-settlement-idUSBRE9A30MM20131104

http://www.businessinsider.com/jj-got-fined-12-billion-because-of-this-drug-2012-4#ixzz2kk0jk42C

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Pandemrix H1N1 swine flu vaccine: a “medical tragedy”

Concerns expressed about GSK’s drug Pandemrix since 2009 have been further substantiated by independent teams of scientists who have published peer-reviewed studies from Sweden, Finland and Ireland, showing the risk of developing narcolepsy after the 2009-2010 immunization campaign was between 7 and 13 times higher for children who had Pandemrix than for their unvaccinated peers.

Picture by Alcibiades

Reddit.com highlights the Reuter’s report by Kate Kelland about around 800 children in Sweden and elsewhere in Europe who developed narcolepsy, an incurable sleep disorder, after being immunized with the Pandemrix H1N1 swine flu vaccine made by British drugmaker GlaxoSmithKline in 2009. Europe’s drugs regulator has ruled that this vaccine should no longer be used in people aged under 20.

Goran Stiernstedt, director for health and social care at the Swedish Association of Local Authorities and Regions, helped to coordinate the vaccination campaign across Sweden’s 21 regions. While estimates vary, he says Sweden’s mass vaccination saved between 30 and 60 people from swine flu death. Yet since the pandemic ended, more than 200 cases of narcolepsy have been reported in Sweden. With hindsight, this risk-benefit balance is unacceptable. “This is a medical tragedy,” he said. “Hundreds of young people have had their lives almost destroyed.”

GSK says 795 people across Europe have reported developing narcolepsy since the vaccine’s use began in 2009. Finland, Norway, Ireland and France have seen spikes in narcolepsy cases and it is alleged that a study to be published in Britain will show a similar pattern in children here.