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PV futures: Pharmacovigilance as a solution to the challenges of tomorrow

Published on 11/03/19 at 12:09pm

Louis Goss asks what the future might hold for the safety of pharmaceuticals and looks into why crucial pharmacovigilance practices offer solutions in an increasingly uncertain world.

In a poem from 1967, countercultural writer Richard Brautigan wrote: “I like to think (and the sooner the better!) of a cybernetic meadow where mammals and computers live together in mutually programming harmony like pure water touching clear sky.”

In describing a technological utopia, Brautigan depicts an idealistic world in which digital technology becomes an integral part of peaceful, pastoral life. Nature and technology merge to form a “cybernetic ecology” in which “deer stroll peacefully past computers as if they were flowers with spinning blossoms” and we are “returned to our mammal brothers and sisters, and all watched over by machines of loving grace.”

For Brautigan this was a world that “has to be!” Thus, in a move towards the idealistic vision he foresaw, Brautigan gave away all 1,500 copies of the short book in which his poems appeared. Today, all of Brautigan’s poetry is available online for free.

However, it is now increasingly hard to entertain Brautigan’s optimistic vision. In a world that is increasingly reminiscent of a digital dystopia, Brautigan’s depiction may feel closer to a default Windows wallpaper than an accurate image of the early 21st century.

That is not to say that the digital revolution hasn’t transformed the way we live our lives. Rather, it seems that technological innovation and the continuous wave of digitalisation has fuelled chaos and disorder, as the fundamentals of society are shaken to their core. The universe of medicines and pharmaceuticals has not been immune to this unabated torrent of change. 

Visions of the 21st century

In a report from 2002, the World Health Organization (WHO) wrote: “Within the last decade, there has been a growing awareness that the scope of pharmacovigilance should be extended beyond the strict confines of detecting new signals of safety concerns. Globalisation, consumerism, the explosion in free trade and communication across borders, and increasing use of the Internet have resulted in a change in access to all medicinal products and information on them. These changes have given rise to new kinds of safety concerns.”

The report warns of the growth of unregulated online markets amidst the increasing prevalence of self-medication practices and the use of traditional and herbal medicines outside of the confines of ‘traditional cultures’.

The British Government’s Office of Science and Technology went one step further in a report from 2005. In essence, the report – titled Drug futures 2025? – outlines four distinct visions of the future of drugs and pharmaceuticals as they might appear in the year 2025.

The scenarios describe a world shaken by “significant advances” in our understandings of the human brain. “As our material situation has improved, attention has turned more and more to our mental state. We do not expect merely to be well fed and housed. We also pursue happiness for ourselves and others. At the same time, we expect more from our brains. As citizens of the knowledge economy, we can access trillions of facts through our fingertips,” the report begins.

The four scenarios – named ‘High Performance’, ‘Neighbourhood Watch’, ‘Treated Positively’ and ‘Dispense with Care’ – each outline different ways through which society might address the period of upheaval caused by fast-paced scientific advancement and the resultant shifts in the way we see the world.

The first scenario, ‘High Performance’, describes an ultra-competitive society in which there is widespread use of so-called “cognition enhancers”. The British economy is reliant on highly skilled “knowledge nomads” who drive economic growth. The UK’s success is thus dependent on attracting this class of highly mobile “elite knowledge workers”, who in turn reap great “rewards” for their contributions to the economy. These people are in part attracted to the UK due to its “progressive” society and laissez-faire economics.

However, this highly competitive world comes at the cost of an increasingly unstable society and a growing class of discontents. Rapid and conspicuous consumption fuels the UK’s trade and production, which is increasingly concentrated in the hands of large, multinational corporations.

“Continuous innovation and the adoption of technology have created many new jobs and industries, but has also destroyed old ones; growth in the service sector has mopped up a lot of unemployment, but the jobs are not always the ones people want; wealth and opportunity have become concentrated in the cities, while rural areas are under threat; and people are ultimately more concerned with their own interests than with those of the wider community,” the report goes on to say.

The high pressure society fuels demand for both performance enhancing and recreational drugs, a demand which is met by an increasingly unregulated market channelling an influx of both legal and illegal drugs into the UK. While the elite use these drugs to enhance their lives (both at work and in their spare time), the growing class of low-paid, precarious workers use these drugs as a means of escape.

In contrast, ‘Neighbourhood Watch’ paints an image in which the UK “is suffering something of an identity crisis and is struggling to find its place in the world”. The UK economy is in decline. Drug use among the middle classes has grown, while drug use among those in poverty has become a part of everyday life. In response, society cracks down on the widespread use of recreational drugs. Science is disregarded in favour of a moral crusade. The negative effects are felt by the UK’s scientific establishment, as mistrust in science grows and funding is channelled elsewhere.

Alternatively, ‘Dispense with Care’ presents a UK in which more medicines are available than ever. Yet the NHS is under severe strain. An ageing generation of “consumer patients” want access to this growing array of innovative and highly expensive treatments, irrespective of the costs. With the NHS (or rather taxpayers) unwilling to fund it, a growing group of well-informed patients moves towards private healthcare. Society comes to regard one’s own health as one’s own personal responsibility. 

Meanwhile, demand is growing among younger patients for treatments for conditions which had once been considered social or psychological. Many consumers thus choose to access new medicines “through unregulated routes, such as the Internet”. Often, those producing these therapies are barely regulated manufacturers in India and China. The collapse of the NHS and the expansion of grey markets in turn have a significant effect on the profits of the pharmaceutical industry, thus leading companies to abandon much of their R&D and “concentrate on lower-risk, higher-value drugs.”

Finally, ‘Treated Positively’ presents us with an image of the UK “facing a number of challenging social and political issues including global warming, terrorism and global equity.” A concerned citizenry, who are increasingly aware of geopolitics and value lifestyle and community over conspicuous consumption, have pushed for higher levels of taxation and regulatory regimes that encourage equality and wealth distribution.

In the context of an increasingly liberal and scientifically literate society, regulators explore the potential of psychedelic drugs as a treatment for conditions such as alcoholism, depression and PTSD. While big drugmakers still dominate the pharmaceutical industry, society sees a “growing number of low-cost specialist manufacturers using 'open source' – collaborative knowledge-based systems that use pharmacogenetics and other research data to create new precision treatments.” Great progress is made in regard to health, as a growing collective of “micro-manufacturers” create precision medicines for deadly and debilitating diseases. However, illicit manufacturers also seize the opportunities created by the open source ecosystem as they begin to create precision recreational drugs, able to target users’ brain reward systems.

The world today

It is not difficult to draw parallels to the present day. In the fourteen years following the publication of the report, there has been an explosion in the growth of unregulated online markets, particularly on the dark web. The first modern ‘darknet market’, Silk Road, was founded in February 2011. As of today, estimates place total darknet drug sales in the region of hundreds of millions of pounds.

Pharmaceutical drugs and prescription medicines are believed to be the most commonly sold drugs online. As noted in an Interpol report from 2015: “The most commonly advertised products on Silk Road 2.0 and Evolution are prescription medicines.” Also, “30% of the total amount of advertised drugs were prescription medicines.” Benzodiazepines, such as anti-anxiety drugs Valium and Xanax, were the most commonly advertised prescription medicines on the original Silk Road’s successor, Silk Road 2.0, in 2015. The increasing prevalence of sales for anti-anxiety medication via illicit online markets would not seem out of place in the high-pressure world of ‘High Performance’ or the consumer patient-dominated society of ‘Dispense with Care’.

In contrast, organisations such as the Multidisciplinary Association for Psychedelic Studies (MAPS), and the Peter Thiel-backed biotech, Compass Pathways, are pioneering psychedelic drugs as legitimate treatments for conditions such as depression, drug addiction and anxiety associated with living with a life-threatening illness.

Equally, the world has begun to see the first signs of the emergence of open source biotechnology; some of the most powerful and widely used biotechnology software tools are already open source. Furthermore, the Open Source Drug Discovery (OSDD) initiative, launched in September 2008, is developing infrastructure through which participants are able to contribute towards the development of novel drugs for neglected tropical diseases, which will then be made available as generics without intellectual property restrictions. More far-reaching initiatives might be seen in the future.

Nevertheless, the recent emergence of therapies costing hundreds of thousands of pounds also conjures up images evocative of the world of ‘Dispense with Care’. While the average cost of drugs for cancer has increased fivefold over the past two and a half decades (from $50,000 per patient in the mid-1990s to $250,000 today), the NHS’ recent rejection of Gilead’s $373,000 CAR T therapy Yescarta on the grounds of cost in August of 2018, may be a sign of things to come.

What is pharmacovigilance?

Pharmacovigilance is the practice of monitoring the adverse effects of pharmaceutical drugs. The foundations of the pharmacovigilance apparatus, as we know it today, were first laid in the latter half of the 20th century. The thalidomide disaster of the late 1950s and early 1960s – and the public outrage it inflamed – was particularly fundamental in shaping the state’s approach to the surveillance of pharmaceutical products on the market.

While previous focus had been placed on pre-market testing, for many, the disaster in which thousands of children were born with malformed limbs, brought to light the necessity for surveillance of the effects of medicines in the real world. Thus, the UK launched the Yellow Card scheme in 1964. Meanwhile, the US had avoided the scandal entirely by preventing thalidomide’s entry into the market in the first place.  

Nicolas Langlitz, an Associate Professor of Anthropology at the New School in New York, expanded on the roots of pharmacovigilance in a paper from 2009: “The FDA gained its power and legitimacy through a number of drug scandals, in which patients had been severely harmed by adverse drug reactions. As a result, it came to see patients as vulnerable subjects in need of protection against industry. This protection was granted by setting up high hurdles to the market. Of course, these measures were criticised from the beginning. The FDA was accused of hampering business interests, slowing down the development of new drugs, and keeping already developed drugs from patients for too long.”

“In the 1980s, these attacks gained momentum. At the time, patient organisations based on diseases – especially the AIDS movement – became increasingly active in the US. Now patients whom the FDA was meant to protect accused it of withholding life-saving medications from them. Instead of being protected and patronised, they wanted to be given the chance to try still experimental drugs in an otherwise hopeless situation. Unwilling to bear with the delays caused by the FDA’s due process, AIDS activists and allied scientists began to organise community-based therapeutic trials and underground tests of new unlicensed drugs in so-called guerrilla clinics.”

The crisis resulted in an unlikely coalition between pharmaceutical companies, AIDS activists, and the neoliberal administrations of the Reagan and Bush era. While pharmaceutical companies sought to profit from quicker access to the market, the activists (fighting for their lives) found allies in a government actively pursuing programmes of deregulation. The far-reaching pharmacovigilance apparatus of today was thus the solution to a shift in focus away from stringent pre-market testing.    

The challenges of tomorrow

It seems likely that the societies of the 21st century will see new ways through which drugs and pharmaceuticals will be developed, sold and consumed. Many of these new practices (as is already apparent in the case of darknet markets) may entirely bypass the structures put in place by regulatory authorities. Thus, as the market becomes more and more difficult to control, pharmacovigilance may have to play an increasingly central role.

Indicative of the need for more thorough and extensive pharmacovigilance is the recent explosion in the popularity of ‘herbal medicines’. As of 2008, approximately 20% of the American population used some form of herbal medicine. The vast majority of herbal medicines, which are classified as ‘dietary supplements’, are not held to the same standards as pharmaceutical drugs. This does not mean, however, that herbal medicines are entirely safe. Reports of side effects and interactions with other drugs are in some cases relatively common. However, due to the relative ease with which many herbal medicines are made, it would be hard to prevent their entry into the market. As such, pharmacovigilance may be the best option in ensuring the safety of drugs in a world in which the prevelance of herbal medicines is increasingly common..

The relaxation of rules around cannabis presents a similar challenge for pharmacovigilance. As noted in a recent op-ed by journalist Malcolm Gladwell in the New Yorker: "the drug North Americans have become enthusiastic about remains a mystery”. Gladwell goes on to point out the lack of science surrounding the effects of cannabis. The situation is complicated by the wide variety of strains, and methods of delivery. Nevertheless, this lack of knowledge has not prevented widespread use of the drug, both in regions where it is legal and in those where it is illegal. Thus, while more clinical trials are a necessity, post-market surveillance will also be vital in understanding the effects of cannabis in the real world.

In both cases it is important that those involved with the distribution of either herbal medicines or cannabis are aware of the potential side-effects of products they are dealing with, and that in turn they are incorporated into the wider pharmacovigilance apparatus. The same must be true for patients. As such, an accessible and far-reaching pharmacovigilance apparatus will be essential. In particular, social media and the internet may provide a means through which patients can be educated on the effects of drugs and in turn report adverse drug reactions, thus contributing towards our understandings of drugs and their effects. Doctors and physicians must also be aware of these trends and the effects they are having on public health; an uncertain future requires agile and versatile systems to ensure the safety of the drugs we use.

Louis Goss

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