It only within the last few months that I have been made aware of the huge scandal that arises from the promotion, sales and use of the painkillers, opioids in the USA. It has been described by Time Magazine as

“the deadliest drug crisis in American history”.

Overdoses of this drug are responsible for the deaths of almost 100 people every day. Since 1999, the number of these deaths has quadrupled. In 2015, drug overdoses caused more deaths than road traffic accidents and gun violence. In 2016, there were nearly 64,000 deaths due to drug overdoses, which roughly the same number of deaths due to the entire Vietnam, Iraq and Afghanistan wars combined. According to the Centers for Disease Control, opiods have contributed to a reduction in life expectancy in the USA between 2000 and 2015.

It all started in 1995 with a prescription painkiller, OxyContin, developed by Purdue Pharma, a privately-owned company (1). At the time, it was regarded as a major breakthrough, because it was long-lasting and would therefore help patients suffering from moderate to severe pain. However, it has been controversial from the beginning because it is closely related to heroin and can be much more powerful than morphine. Traditionally doctors have been reluctant to prescribe opioids because of genuine fears that they are likely to be addictive. David Kessler, who is a former commissioner of the Food and Drug Administration (FDA) has stated that

“Few drugs are as dangerous as the opioids.”

Because of the extent of the ill-health and deaths linked to the use of these drugs, this is quite rightly regarded as a massive public health issue in the USA. Steps are being taken to restrict the amount of opioids that can be prescribed by doctors. However, this has led to an explosion in the demand for illegal substitutes that have similar narcotic effects. These include heroin, fentamyl, carfentanil and U-47700. These are likely to be more harmful than legalised opiods because there are no official safety standards and quality control is probably non-existent. Between 2002 and 2015, deaths from heroin overdose increased by a factor of six.

In total, since 1999 there have been 200,000 deaths of Americans from overdoses related to OxyContin and other opioids, which have prescribed. The American Society of Addiction Medicine reckons that four out of five people who turn to heroin have started with prescription painkillers. The most recent figures from the Centers for Disease Control and Prevention suggest that a hundred and forty-five Americans now die every day from opioid overdoses.

It is extremely revealing to discover how OxyContin was launched. Before the drug was released, the Purdue company conducted focus groups with doctors, which revealed that the major hurdle to overcome was the inherent concern about “abuse potential”. It just happened that leading doctors such as Russell Portenov at the Memorial Sloan Kettering Cancer Center were outspoken about the need to tackle untreated chronic pain. He saw great potential in the use of opioids to address this issue.

He was highly critical of the reluctance of physicians to use them for chronic pain. Subsequently in 1997, the American Academy of Pain Medicine and the American Pain Society published a statement regarding the use of opioids to treat chronic pain. Both Dr Portenoy and Dr David Haddox, who chaired the committee that produced the statements received payments from Purdue.

 

In 1995, OxyContin was approved by the FDA for the treatment of moderate to severe pain. This decision was taken even though Purdue had not conducted any studies to determine how addictive the drug was likely to be. There was also no information on the potential for abuse. Furthermore, the FDA allowed the company to claim that the drug was actually safer than existing painkillers available on the market. The FDA official in charge of the approval process left the agency shortly afterwards and within two years he was appointed to a position at Purdue.

However, the marketing campaign devised by Purdue emphasized that the drug could be prescribed not only for severe short-term pain that occurs during surgery or cancer but also for less acute, longer-lasting pain: arthritis, back pain, sports injuries, fibromyalgia. Subsequently it was revealed that Purdue found out that many doctors assumed, wrongly, that the drug was less potent than morphine. The company was not slow to exploit this misconception. Clearly the strategy was to aim for the widest possible market.

There was a huge effort to target the medical profession. Purdue had a bank of speakers who were paid to make presentations at medical conferences that emphasized the benefits of the drug. Doctors were invited to attend with all their expenses paid. Documents subsequently released showed that those doctors who attended these sessions in 1996 prescribed OxyContin twice as often as those who did not. This was re-inforced by advertising in medical journals, sponsored websites, videos featuring satisfied patients and an assortment of supporting material including fishing hats, plush toys and luggage tags. Furthermore, there were videos of testimonials from pain specialists, which were circulated to tens of thousands of doctors. In other words, it was a very hard sell.

According to Keith Humphreys, a professor of psychiatry at Stanford, many doctors were strongly influenced and probably accepted the information in good faith. He said:

“The level of influence is just mind-boggling. Purdue gave money to continuing medical education, to state medical boards, to faux grassroots organizations.”

The reality was quite different. For example, the sales representatives were instructed to reassure doctors that of the patients who used OxyContin, fewer than 1% became addicted even though Purdue had data indicating that the addiction rate was 13%.

Shortly after OxyContin was released, there were signs that it was being abused. Rather ironically, the labels came with a warning that:

“Taking broken, chewed or crushed OxyContin tablets could lead to the rapid release and absorption of a potentially toxic dose.”

So, it is no great surprise to learn that many people actually used this information and did exactly as instructed. In fact, some patients began trading the pills on the black market. Many doctors were easily manipulated by their patients and/or (corrupted by the money involved) This resulted in the establishment of so-called pill mills, which were pain clinics that thrived on a wholesale business of issuing OxyContin prescriptions.

There was not the slightest acceptance by Purdue that the drug was addictive. On the contrary, the company went on the offensive and insisted that the issue was recreational drug users who were not following the instructions for use.

 

The company did not pull the drug from shelves, however, or acknowledge that it was addictive. Instead, Purdue insisted that the only problem was that recreational drug users were not taking OxyContin as directed.

“Their rap has always been that a bunch of junkies ruined their product,”

Keith Humphreys, the Stanford professor, said. In 2001, Michael Friedman, Purdue’s executive vice-president, testified before a congressional hearing convened to examine the alarming increase in opioid abuse. The marketing of OxyContin had been “conservative by any standard,” he maintained.

“Virtually all of these reports involve people who are abusing the medication, not patients with legitimate medical needs.”

The key to the success of OxyContin is that it lasts for 12 hours, which is double that of other generic drugs. If this is the case, then it means that patients do not have to wake up in the middle of the night to take the medication. It is now evident that it was being promoted on a false prospectus. Even worse, because OxyContin is related to heroin, patients can experience excruciating symptoms of withdrawal, including an intense craving for the drug.

An investigation by the Los Angeles Times found that:

  • “Purdue has known about the problem for decades. Even before OxyContin went on the market, clinical trials showed many patients weren’t getting 12 hours of relief. Since the drug’s debut in 1996, the company has been confronted with additional evidence, including complaints from doctors, reports from its own sales reps and independent research.
  • The company has held fast to the claim of 12-hour relief, in part to protect its revenue. OxyContin’s market dominance and its high price — up to hundreds of dollars per bottle — hinge on its 12-hour duration. Without that, it offers little advantage over less expensive painkillers.
  • When many doctors began prescribing OxyContin at shorter intervals in the late 1990s, Purdue executives mobilized hundreds of sales reps to “refocus” physicians on 12-hour dosing. Anything shorter “needs to be nipped in the bud. NOW!!” one manager wrote to her staff.
  • Purdue tells doctors to prescribe stronger doses, not more frequent ones, when patients complain that OxyContin doesn’t last 12 hours. That approach creates risks of its own. Research shows that the more potent the dose of an opioid such as OxyContin, the greater the possibility of overdose and death.
  • More than half of long-term OxyContin users are on doses that public health officials consider dangerously high, according to an analysis of nationwide prescription data conducted for The Times.”

In 2007, the US Justice Department charged the company and three of its executives with fraud based on the marketing campaign, which claimed that OxyContin was less addictive than other painkillers. The defendants pleaded guilty and were ordered to pay $635 million.

Nevertheless, there was a failure to address the fact that the drug was not effective for 12 hours in many people. The response of Purdue was to encourage the doctors to increase the dose if this happened but, of course, this increased the likelihood of addiction. The high dose version was more profitable, and the sales representatives were encouraged to push this as hard as they could.

 

Conclusion

It is impossible to exaggerate the extent of this absolute disaster. The number of deaths, that is at least 200,000 is just the tip of the iceberg. For every death there are many more that suffer from addiction that has been directly caused by complying with the advice from their doctors. The personal human tragedies are dramatically illustrated in a recent issue of Time Magazine (3). It is as plain as daylight that the pharmaceutical company involved has blatantly manipulated data, ignored inconvenient facts, and disregarded the law. The FDA has demonstrated that it is incapable of exerting any kind of effective control over the drug industry.

Although all of this is new to me, I am not in the least surprised. There is an unholy alliance between government, industry and the medical profession that enables bad drugs to be placed on the market, which do much more harm than good. The drive to make huge profits is the primary objective but the costs in terms of death and suffering for individuals and their families are incalculable.

References

  1. P K Keefe (2017). “The Family That Built an Empire of Pain” New Yorker 30th October
  2. http://www.latimes.com/projects/oxycontin-part1/
  3. James Nachtwey (2018). “The Opioid Diaries” Time 5th March 2018