17 January 2019

American patients need a drugs system they can trust


When you look at developments in global health since the 1800s, it’s safe to say that the 21st century is not a bad time to be alive. Global life expectancy has more than doubled in the last 200 years, the number of deaths of children under five decreased by 58 per cent between 1990 and 2017, and HIV infection rates are being brought under control. Since the creation of the first vaccine, an estimated 730 million lives worldwide have been saved, smallpox has been wiped out and polio is nearing the point of eradication. Antibiotics have also been a massive game-changer, revolutionising modern medicine and making previously incurable diseases like pneumonia and tuberculosis treatable.

With increasing medical discoveries and drug development, most ailments are now treated using pharmaceutical products. In fact, in the US drug prescription has increased by 85 per cent between 1997 and 2016, according to a 2017 survey, increasing from 2.4 billion to 4.5 billion a year (though the American population increased by 21 percent between those years).

Pharmaceutical companies undertake valuable research and spend billions of dollars to develop drugs that improve our healthcare and extend our lives. But the ‘pharmaceuticalisation’ of medicine and the way that the drug industry works may be more harmful than we think. A study from Johns Hopkins University suggests that death from medical errors and treatment-induced illness has become the third leading cause of death after heart disease and cancer in the US, responsible for somewhere in the area of 250,000 deaths a year.

America has become a ‘drug nation’, with various inducements for doctors to prescribe pharmaceuticals. A research project undertaken by CNN health found that many doctors in the US received financial incentives from big companies to prescribe certain products, and suggested that opioid manufacturers are more likely to pay doctors who write the most prescriptions for their drugs. So the more they prescribe, the more money they make.

The increasing popularity of prescription opioids, otherwise known as painkillers, has had devastating consequences including overdoses and widespread addiction. The US Department of Health and Human Services reported that between 2016 and 2017, 2.1 million people had an opioid use disorder and 42,249 people died from overdosing.

The overprescription and misuse of opioids have garnered plenty of attention in the US media, but it is only one part of a broader problem of patients being prescribed the wrong drugs. According to a Consumer Reports study, “the amount of harm stemming from inappropriate prescription medication is staggering. Almost 1.3 million people went into US emergency rooms due to adverse drug effects in 2014, and 124,000 died from those events.”

According to Statista, the total revenue of the global pharmaceutical market in 2017 was $1.143 trillion, and roughly half of it originated from the US and Canada (even though the region makes up less than 5 per cent of world population). The American drug industry largely owes its high profit margins to ‘blockbuster drugs’, that generate annual sales of at least $1 billion for the company. Problems emerge when those drugs become so valuable to a company that the risk of serious side effects is concealed in order to maximise sales. The deliberate obfuscation of drug risks found in clinical trial results points towards systemic problems with transparency.

Clinical trials were introduced to establish whether drugs work and are safe to use. But the drug trial system that’s meant to protect us from pharmaceutical disasters is not as transparent as one might imagine. Approximately 81 per cent of clinical trials are led by private companies and commercially funded, and their product approval is obtained through other companies and regulators. Although industry sponsored clinical trials can be beneficial and effective in innovation and drug discovery, there are concerns regarding bias in the results of these trials and the financial conflicts of interest. According to the Indian Journal of Health Sciences and Biomedical Research, industry-funded trials conclude with positive results far more often than trials funded by other sources. This not only affects the credibility of these industry-led clinical trials, but can mislead physicians “to follow a flawed therapy of their patients”.

Another issue lies in the publication of the trials and drug results and the public’s access to information on drug risk. Although hundreds of thousands of clinical trials are conducted each year, the National Center for Biotechnology Information (NCBI) found that only about half of all clinical trials were published, and that large multicentre trials with non-commercial funding were more likely to be published than other trials. This shows that even though 81 per cent of trials are commercially funded and led by private pharmaceutical companies, the industry is less likely to publish the trials — raising some concerns about transparency.

The trials are also often written up by ghostwriters and published in leading medical journals to help lend the product extra credibility. According to the NCBI, “corruption of the scientific literature through ghostwriting persists in medicine due to the enormous profits for all stakeholders, including the pharmaceutical industry that creates the publication strategy”, suggesting that ghostwriters often polish results and conceal the risks and side effects entailed by the pharmaceuticals. This not only creates an issue of confidence between doctors and pharmaceutical companies, but also between patients and doctors. Patients put their faith in their medical practitioners, who themselves trust the often inadequate clinical trials conducted by private drug companies. This deliberate obfuscation of side effects to promote sales leads to a misprescription of unnecessarily high-risk drugs to patients with common medical problems that should be treated with less powerful pharmaceuticals.

One highly prescribed brand of antibiotics, Cipro, has been dubbed ‘the deadliest antibiotic on the market’ because of its potentially permanent and disabling side effects. Cipro, or ciprofloxacin, is part of a group of antibiotics called fluoroquinolones which eliminate bacteria by interfering with DNA replication. But research has shown that fluoroquinolones can cause DNA breaks in human cell lines, damaging the enzymes which allow cells to replicate and heal. That can lead to potentially permanent damage to tendons, muscles, joints, nerves and the central nervous system. What’s more, the fluoride in the antibiotic allows penetration of impermeable tissue in the human body such as the brain, which can cause psychiatric symptoms such as mania, severe insomnia, ‘brain fog’, memory loss and acute psychosis. This disabling adverse drug reaction is known as ‘fluoroquinolone toxicity syndrome’.

Despite the warning signs, doctors are still prescribing fluoroquinolones for common infections such as bronchitis, UTIs and sinus infections, instead of leaving them as a last resort. Indeed, fluoroquinolones are some of the world’s most commonly prescribed antibiotics — in 2015, there were as many as 32.5 million prescriptions in the US alone. However, patients have been assiduous in trying to expose the drugs’ side-effects with blogs such as ‘Floxie Hope’, ‘My Quin Story’ and the ‘Fluoroquinolone Toxicity Live Chat Group’, where thousands of people gather to share their experiences and information about the antibiotics. Lack of awareness of the drug’s dangerous risks still persists but the US Food and Drug Administration has made some efforts to warn doctors about the pharmaceuticals.

Although the FDA, responsible for protecting and promoting public health in the US, has known about fluoroquinolone toxicity since 2001, the agency only added a first ‘black box’ warning in July 2008 for the increased risk of tendinitis and tendon rupture, and in August 2013 it required an updated labelling to describe the risk of potential irreversible peripheral neuropathy (serious nerve damage).

In 2016, the FDA warned about fluoroquinolones being responsible for “potentially permanent side effects involving tendons, muscles, joints, nerves and the central nervous system”. A news release published by the agency in 2018 updating on fluoroquinolone antibiotics risks stated that “because the risk of these serious side effects generally outweighs the benefits for patients for [uncomplicated infections], the FDA determined that fluoroquinolones should be reserved for use in patients with these conditions who have no alternative treatment options”.

The concealed drug risks in the trial result publications make it more difficult for medical practitioners to recognise adverse drug reactions like fluoroquinolone toxicity in their patients. As such, many victims of adverse drug reaction are misdiagnosed with other medical issues and are advised to undergo treatments which can further damage their health. One case, reported in Nature, revealed that some doctors had dismissed the patient’s symptoms as psychosomatic. Whether the doctors deliberately concealed their knowledge of this adverse drug reaction to avoid admitting responsibility and from fear of lawsuits and accusations, or whether fluoroquinolone toxicity was genuinely unknown to them is irrelevant. The lack of transparency in the industry continues to mislead doctors and generate critical, life-altering problems for some patients.

Drug risk misconception and the overprescription of pharmaceuticals is far from the only problem in the industry. The overwhelming financial power of the pharmaceutical industrial complex encourages rent-seeking, with companies fleecing customers by continually increasing the costs of treatment without justification. The effective oligopoly in Big Pharma has enabled a small group of very large companies to charge patients exorbitant amounts, increasing costs both to consumers and the federal government, which subsidises health through the Medicare and Medicaid programmes.

In their recent book The Myth of Capitalism: Monopolies and the Death of Competition, Jonathan Tepper and Denise Hearn document how a lack of competition, aided and abetted by supine regulators, has led to ordinary Americans paying through the nose for their healthcare. The authors use the example of Syprine and Cuprimine, two relatively inexpensive drugs used for the treatment of Wilson’s Disease. For years the drugs were priced at just $1. However, when Merck sold the rights to the drug to Valeant Pharmaceuticals in 2010, the price ballooned to around $25,000 for just one month’s supply.

Similarly, Valeant raised the price of lead poisoning treatment by more than 2,700 per cent in a single year. Although the original cost was $950, the voluntary group US Poison Control now has to pay $5,000 per gram. It’s particularly galling given the ingredients cost just $0.33 per gram if ordered from a lab catalogue. Over the border in Canada, patients pay $15 for the same treatment — 33,300 per cent less than what Americans pay.

The average American spends more than $1,000 a year on prescription medications, 40 per cent more than Canadians and double what Germans spend. Although drug production is expensive in some cases, the astronomical price increases by pharmaceutical companies are the result of pliant regulators and a lack of competition.

A big part of the problem is patents, which are intended to let companies reap the rewards of innovative treatments for a defined period of time. However, instead of letting the patents lapse and the drugs become available as generic treatments, companies are now able to reformulate the drugs and make tiny changes to secure a fresh patent, perpetuating their position as price-setters in that market and, bluntly put, screwing over consumers.

The US Congress has recently come up with some ideas on how to bring down drug prescription prices, which include letting patients import drugs from Canada, transforming the patent system and letting the government manufacture certain drugs. But the issues in the Big Pharma industry are not just about cutting costs, they’re about protecting patients and consumers that put their faith in medical care services.

One step which would empower American patients would be to make clinical trial results available to the public and ensure drug trial publications are independently verified, so that doctors are not misled to wrongly prescribe pharmaceuticals. There is also a strong case for reviewing the financial relationships between doctors, medical institutions and pharmaceutical companies. But above all, transparency and competition can help deliver safer and more affordable drugs to US patients without stifling the innovation that drives pharmaceutical breakthroughs.

Lucy Cotillon is an intern at CapX.