The opioid crisis: ‘In 2021, no one can claim that these drugs aren’t addictive’

Despite all the revelations in the United States about the opioid epidemic – and the role played by Purdue Pharma – there are people in Israel who are marketing them with the claim that use will only lead to addiction in 1 percent of cases. In the second part of Shomrim’s ‘The Prescription Plague’ series, we turn to the drug companies and examine their relationship with the medical establishment. But is asking them “like asking a cat what it thinks about eating mice”? Their response: “Drug companies have no intention or ability to sway the opinion of medical researchers.”

Despite all the revelations in the United States about the opioid epidemic – and the role played by Purdue Pharma – there are people in Israel who are marketing them with the claim that use will only lead to addiction in 1 percent of cases. In the second part of Shomrim’s ‘The Prescription Plague’ series, we turn to the drug companies and examine their relationship with the medical establishment. But is asking them “like asking a cat what it thinks about eating mice”? Their response: “Drug companies have no intention or ability to sway the opinion of medical researchers.”

Despite all the revelations in the United States about the opioid epidemic – and the role played by Purdue Pharma – there are people in Israel who are marketing them with the claim that use will only lead to addiction in 1 percent of cases. In the second part of Shomrim’s ‘The Prescription Plague’ series, we turn to the drug companies and examine their relationship with the medical establishment. But is asking them “like asking a cat what it thinks about eating mice”? Their response: “Drug companies have no intention or ability to sway the opinion of medical researchers.”

Daniel Dolev

Illustration: Moran Barak

December 10, 2021

Summary

In

the first part of this series, we exposed what went on in the previously classified meetings of a special Health Ministry committee, established to fight the opioid epidemic in Israel. We highlighted the extent of the phenomenon. The second part will examine those responsible for creating the crisis. Alongside the Food and Drug Administration, which approved these drugs in what its former director described as “one of the great mistakes of modern medicine,” the main culprits for the opioid crisis that has blighted the U.S. for the past two decades is clear: the drug companies.

As we reported in the first part of this series, the finger of blame in the U.S. is pointed firmly in the direction of Purdue Pharma, which was owned by the Sackler family, and which aggressively marketed its slow-release opioid painkiller OxyContin. Last year, Purdue Pharma was convicted as part of a plea bargain on several counts relating to the marketing of its drugs and was fined some $8 billion. Meanwhile, many states are still engaged in compensation talks with the company, which has since filed for bankruptcy. In September, it was reported that a $26-billion deal had been agreed with four other companies that produced opioids, including Johnson & Johnson.

The Health Ministry is well aware of the statistics: at the fourth meeting of the opioid taskforce, which took place in September 2019, its members were shown a presentation summarizing the main findings of Itay Babli and Dr. Haim Mahal, who examined the role of drug companies in the American crisis. They highlighted several methods used by the drugs companies – again, mainly Purdue – to increase the number of opioid prescriptions issued by physicians. Their aggressive marketing campaigns focused on deceiving the medical community into believing that these were safe, nonaddictive drugs. To this end, Purdue doubled the number of medical sales reps it employed, using advertising directed both at medical professionals and the public.

There were also less orthodox marketing methods employed, such as funding organizations and NGOs representing patients suffering from chronic pain. In practice, according to Babli and Mahal’s research, drug companies gave these organizations marketing material stressing the false claim that these drugs were nonaddictive, while, at the same time, using them to put pressure on decision makers not to limit prescriptions.

The partnership with these organizations was fruitful. The American Pain Society, financed and coordinated by Purdue, promoted the addition of a fifth vital sign of patient wellbeing – the pain scale. The scale was adopted wholesale and became part of every routine examination. In 2016, once the extent of the opioid epidemic – and the reasons for it – became clear, the scale was abandoned by the American Medical Association.

Purdue also invested heavily in academic research, all the time promoting positions that fit its narrative in the scientific community. For example, it promoted the narrative that there is a less than 1 percent chance of addiction to OxyContin, basing that claim on a 1980 letter to the editor of the New England Journal of Medicine. The 1 percent figure, however, came from a study focusing on cancer patients, who were prescribed opioids for acute and not chronic pain. Nonetheless, thanks to Purdue’s marketing machine, it was quoted more than 300 times in various academic papers.

“I would be very surprised if you could find a single professional who claims that these drugs are nonaddictive,” Dr. Shaul Lev-Ran – cofounder of the Israel Center on Addiction and deputy director of Lev Hasharon Medical Center – told Shomrim. “It’s inconceivable that anyone would make that argument in 2021. It is an unequivocal fact that these are addictive drugs.”

NYC: Rally Against Purdue Pharma Bankruptcy Ruling, August 9, 2021. Photo: Reuters
Hadas Ziv, Physicians for Human Rights: “The original sin is the link between drug companies and the medical community and why the medical community has reached this situation. It’s because the state doesn’t give enough funding for academia and research, so doctors and researchers have become increasingly dependent on donations from bodies like drug companies. People tell me not to throw the baby out with the bathwater, but I think that we need a complete overhaul of policy on this matter."

The economic link between physicians and drug companies

Some of the issues that allowed prescription opioids to become such a massive problem in the United States are not relevant in Israel. Here, for example, drug companies are not allowed to advertise their products directly to the public. However, other marketing avenues, which were the cornerstone of the American crisis, are also available here. For example, at a committee meeting discussing the causes of the crisis in the United States, members spoke about the physician satisfaction surveys that patients are asked to complete after their treatment. Since physicians do not want to get a low score from their patients, they often sought to please them by prescribing opioids for immediate pain relief.

“You can talk about the Americans all you like, but here in Israel we do the same every day,” said Dr. Daniel Flusser, head of the Internal Medicine Department at Soroka hospital, at one meeting of the committee. “At the Internal Medicine department at Soroka, there’s a pilot whereby patients are sent a text message, asking them to respond immediately whether they’re satisfied or not. I get a daily report on patient satisfaction, in addition to annual and quarterly reports.”

Dr. Ruth Edry, head of the acute pain unit at Rambam hospital, highlighted another overlap between Israel and the United States. “There are some drug company sales reps wondering around inside hospitals,” she said when invited to address the committee. “In our hospital, there are two female reps pushing Percocet and Rokacet [opioids marketed in Israel by Taro Pharmaceuticals]. Every time they come to the hospital, there’s a spike in the number of prescriptions for Percocet and Rokacet. It’s no coincidence. It doesn’t matter how many times I brief the residents beforehand.

“Their system is simple: they meet with our youngest, least experienced interns and they give them a couple of articles saying it’s the best drug in the world and it’s great for patients. There’s no medical oversight. This is a problem that needs to be addressed at the highest levels of the Health Ministry. That’s why it was important for me to raise it here.”

Taro, for its part, rejects this allegation. A statement sent to Shomrim stated that, “Taro acts entirely in accordance with Health Ministry instructions, which dictate what is acceptable behavior for drug companies in Israel. Similarly, Taro acts in the same way when it comes to the lawful dissemination of information to medical professionals. For the sake of clarity, we would add that Taro’s representatives never use the kind of superlatives described by the doctor from Rambam hospital.”

The committee is yet to complete its work, but members are due to vote soon on recommendations to limit the prescription of opioid painkillers. Of all the experts to address the committee, it seems, ironically, that the two people who sounded most concerned by the financial ties between drugs companies and medical professionals were Hadas Ziv and Nadav Davidovich, from Physicians for Human Rights, who were not committee members but were invited to address the panel several times.

“The original sin is the link between drug companies and the medical community and why the medical community has reached this situation,” Ziv told Shomrim. “It’s because the state doesn’t give enough funding for academia and research, so doctors and researchers have become increasingly dependent on donations from bodies like drug companies. People tell me not to throw the baby out with the bathwater, but I think that we need a complete overhaul of policy on this matter.”

Among the recommendations proposed by Physicians for Human Rights is a call for a ban on drug companies funding medical conferences, as well as a complete ban on the use of opioids, except for terminal cancer patients and in emergency situations. For those already addicted, the drug companies should be obligated to fund their rehabilitation, according to PHR.

In a conversation with Shomrim, Ziv was also highly critical of the decision to invite drug companies to appear before the committee. “Several committee members were also against it,” she said, “and couldn’t understand why we would invite the very people who created the crisis to address the committee. But they were still invited. I think that’s like asking a cat its opinion on eating mice.”

The Health Ministry responded: “The committee was convened to formulate and present recommendations for patient wellbeing. Within that framework, it is important to listen to everyone involved in the health system, so we allowed representatives of the drug companies to appear before the committee. We reject arguments that they should not have been invited.”

OxyContin maker Purdue Pharma pleads guilty to criminal charges, New Jersey, U.S., court hearing on November 24, 2020. Photo: Reuters
“You can talk about the Americans all you like, but here in Israel we do the same every day,” said Dr. Daniel Flusser, head of the Internal Medicine Department at Soroka hospital, at one meeting of the committee. “At the Internal Medicine department at Soroka, there’s a pilot whereby patients are sent a text message, asking them to respond immediately whether they’re satisfied or not. I get a daily report on patient satisfaction, in addition to annual and quarterly reports.”

Israeli experts: “These drugs got a bad rap”

Not everyone, however, agrees. Notwithstanding evidence that Purdue Pharma distributed misleading information to market its drugs, even today there are some people keen to promote the statistic claiming that there is a less than 1 percent chance of becoming addicted to opioids. One such body is the National Center for Pain Medicine, established by Dr. Itay Goor-Aryeh and Dr. Silviu Brill.

The center’s internet site has a section dealing with opioid painkillers. According to the information there, “these drugs have an unjustifiably bad reputation. The public and many doctors think that they’re addictive and dangerous. But pain experts argue that that opioids are an excellent treatment option which, in 99 percent of cases, does not lead to addiction ... The percent of patients who become addicted to opioids is low and, it seems, is less than 1 percent.”

These words appear on the center’s website, even though Goor-Aryeh and Brill – along with Prof. Lev-Ran, Dr. Yael Delayahu and Dr. Daniel Feingold – coauthored a 2017 study of almost 1,000 chronic pain sufferers. That study found that at least one in six would become addicted. In percentages, that means that between 17 percent and 50 percent of opioid painkiller users would become addicted to them; according to some of the definition, the addiction rate would be as high as 50 percent.

Brill and Goor-Aryeh are far from fringe figures in pain management. Goor-Aryeh is head of the Israel Pain Association, a nonprofit dedicated to “promoting the treatment and understand of pain.” Brill is a former director of the IPA and currently serves on its supervisory panel. In a conversation with Shomrim, Brill was asked how he and Goor-Aryeh are signatories to a study which found that up to 50 percent of chronic pain sufferers treated with opioids would become addicted, while, at the very same time, his website claimed that there is no such danger in 99 percent of cases. His response was that the difference was in the length of treatment.

“If a patient comes to me with severe pain and I prescribe him or her opioids for a week, or two or three, then the chances of addiction are very low. It also depends on the disease. If I am treating a terminal cancer patient, I’m not too concerned about addiction. We need to make the differentiation very clear when looking at statistics. Most patients do not become addicted.”

Brill also stressed the difference between physical dependency and addiction. “Physical dependency happens to a lot of people, in far greater numbers. Addiction is a very different matter and the figures are very different. When patients with physical dependency stop taking the drug, they experience withdrawal symptoms, which pass within a few days. You need to understand that all these patients are being treated for some condition or extreme pain. No one is giving out opioids like candies. They have been given every standard type of treatment and are given opioids when all else fails.”

38,000 shekels from a drug company

As mentioned above, one significant issue that Physicians for Human Rights highlighted at the opioid committee meetings was the economic ties between drug companies and doctors.

Here’s one example: Cross-referencing information from the Registrar of Associations with data from the Health Ministry shows that in 2018 the annual budget of the Israel Pain Association, headed by Goor-Aryeh and Brill, was 128,000 shekels. One third of this came from donations from Rafa Laboratories, the Israeli company which markets the drugs that have become synonymous with the opioid epidemic – OxyContin, fentanyl patches, Targin and so on. Similar findings were found for 2017.

The information available on the Registrar of Associations website does not reveal the overall budget for the IPA in 2019, but, according to Health Ministry data, it continued to receive a donation of 38,000 shekels from Rafa. Officially, these donations were to be used for “supporting educational activity in the study of pain,” “research grants for selected members of the association,” and “funding the participation of two association members in a cannabis conference in Barcelona.”

Rafa Laboratories was a subsidiary of Purdue Pharma, which manufactured and marketed its drugs in Israel. At the end of 2020, the company was purchased by FIMI Opportunity Funds, the largest private equity firm in Israel. This was possible because of the financial woes facing Purdue, which faced billion-dollar lawsuits in the United States.

Is there anything wrong with that picture? “Donations came from all the companies,” Brill told Shomrim in response. “Most of the money is spent on the educational needs of our experts, as well as the nurses and medical teams. It doesn’t matter whether the money comes from a company that manufacturers antibiotics or opioids; there’s no connection between given money and how we use it. A large proportion of our budget every year is spent on research grants. So, it doesn’t really matter who gives us the money. There’s a donation, and then there’s competition for research funding. The people funding the research don’t know where the money is being spent. There’s no direct contact. I can tell you that most of the research we funded did not deal with opioids at all.”

Dr. Itay Goor-Aryeh, the current head of the Israel Pain Association, told Shomrim that the association’s annual budget is 900,000 shekels and that, “commercial companies pay 300,000 shekels a year for advertising booths at our conferences, and for bringing lecturers from overseas.” Shomrim asked Goor-Aryeh to explain where get got those figures, which are different from those published by the Registrar of Associations and the Health Ministry. He did not respond.

Goor-Aryeh also argued that, “Rafa Laboratories does, indeed, give the Israel Pain Association money amounting to around 3 percent of our annual turnover, for booths are conferences and lecturers. Each company pays the same. In addition, the company funds research grants totaling 20,000 shekels a year, as part of the annual conference. The committee which selects the recipients of the grants has no connection with the company and does not inform the company who has been awarded the grant. To the best of my recollection, the winning studies have nothing to do with opioids. Rafa Laboratories’ support of conferences is advertised in the brochures of these conferences, just like the other companies, and I welcome their investment in pain research.”

Photo: Reuters
Dr. Silviu Brill: “Donations came from all the companies. Most of the money is spent on the educational needs of our experts, as well as the nurses and medical teams. It doesn’t matter whether the money comes from a company that manufacturers antibiotics or opioids; there’s no connection between given money and how we use it."

The committee member who wrote an opinion for a drug company

In recent years, Rafa Laboratories has donated money to nearly every Israeli hospital, as well as to various research funds. Between 2016 and 2019, however, the biggest beneficiary of this generosity was the Israel Medical Association, which received an annual handout of between 116,000 and 144,000 shekels.

It was only in 2019 that the Health Ministry started to reveal the purpose of donations to medical organization. It is impossible, therefore, to determine whether the IMA used the money for promotional material, research or conferences linked to Rafa’s painkillers.

At the same time, the IMA issued a policy statement in 2016, the title of which was “Opioid treatment for chronic pain in non-oncological patients.” Despite the fact that this document bore the logo of the IMA, which also distributed it among its members, it was written in the name of the Israel Pain Association, the Israel Associated of Family Doctors, the Israeli Association of Clinical Pharmacology, the Israel Psychiatric Association and the Israeli Society of Addiction Medicine.

The official position of these organizations, which appears explicitly in the IMA document, is that, “opioids should continue to be an important and significant part of the arsenal of treatments for pain. At the same time, physicians must use them in a responsible and proper manner.”

Among the signatories on that document are Brill and Goor-Aryeh. Another signatory is Prof. Elon Eisenberg, who recently wrote a medical opinion for the Manufacturers Association of Israel, which also represents drug manufacturers. That opinion, which was presented to the Health Ministry’s opioid committee, expressed opposition to the imposition of any restrictions on the sale of opioids. Other experts who signed the policy paper include Prof. Lev-Ran and Dr. Paola Rosca, the director of the Health Ministry’s Department for the Treatment of Substance Abuse.

Perhaps the most interesting name to appear on the document is that of Prof. Pesach Schwartzman, a skeptic who even disputes the use of the phrase ‘opioid epidemic.’ According to Schwartzman, Israel is in a far better place than the United States and warns against “throwing out the baby with the bathwater.”

In May 2021, Schwartzman wrote a medical opinion for two drug companies – Taro and Rafa Laboratories – as part of their defense against a class-action suit that was filed against them. The opinion is very detailed and takes up 172 pages. In response to a question from Shomrim as to whether he does not see any problem with being paid to write medical opinions for drugs companies while serving on a committee charged with formulating policies vis-à-vis those companies’ products, Schwartzman replied in the negative. “I can’t see the problem,” he said. “I am just one member of the committee. And I’m the only one with data. [Over the course of 20 years, Schwartzman collated information about the use of opioids among members of the Clalit HMO – DD]. The whole festival surrounding opioids isn’t based on statistics, it’s based on a feeling. I don’t see any problem, since I still present the same views that I presented beforehand.”

Whether or not it’s a festival is arguable, but more and more statistics are becoming available. Among them is the shocking figure presented to the committee by Tal Morgenstern, a senior Health Ministry official, who revealed that, in 2018, more than 9 percent of the Israeli population had been prescribed long- and short-term opioid painkillers. That adds up to about 800,000 people – up from 700,000 in 2014. That’s a 16 percent increase over just five years.

Further figures were presented by Oren Miron, a doctoral researcher at Ben-Gurion University, who began looking into opioids when he was a research associate at Harvard Medical School. According to Miron’s research, in the decade ending in 2018, the number of opioids consumed by members of the Clalit HMO rose by a factor of 2.2. Details of the study appear in the first part of this series and, in short, they show that, while the use of weaker opioids dropped during that period by 45 percent, the use of stronger, more addictive drugs – especially fentanyl – increased threefold. “[Fentanyl] is usually prescribed for long-term courses. Once, it was given almost exclusively to terminal cancer patients, but now we’re seeing it prescribed to the general population. I spoke to one soldier who broke his arm during his military service and was prescribed very strong opioids. He got addicted and nearly paid with his life. That is the most worrying thing.”

“We do not have good enough data about the number of Israelis who are addicted to opioids on Israel,” Prof. Lev-Ran told Shomrim. “But if you take the information about the number of people who are prescribed these drugs, and the findings about addiction rates among users, the most conservative figure is one in six people becoming addicts. The plague is getting worse.”

Responses

“Drug companies have no intention or ability to sway the opinion of medical researchers, even more so physicians”

Rafa Laboratories said in response: “Opioids are an important element in the treatment of medium and extreme pain, in cases when other painkillers have proved ineffective – such as for cancer patients, orthopedic patients and burns victims. The prescription of these drugs is done with extreme care by the doctors in charge of the treatment and in accordance with the strict regulations issued by the Health Ministry. The drugs are only prescribed to patients for whom more conservative treatments have failed.”

In relation to its donations, the company said that, “it is common practice in the field of medicine for drugs companies to find some of the activities of the medical community, including the Israel Medical Association and other official bodies. It should be stressed that this support is given in accordance with strict ethical rules, but those of the drugs companies and the professional bodies and are fully transparent. All donations are made directly to the associations and the drugs companies have no control over the content, the professional comments, publications or activities – not over where the money is spent.”

The response continued: “The ethical codes of Rafa Laboratories and the Israel Medical Association do not allow for payment for the writing of a position paper or professional instructions. The drug companies have no intention and, indeed, are unable, to sway the judgment of researchers – even more so doctors. In any case, any attempt to compare between Israel and the United States in terms of the misuse of opioids is fundamentally flawed from every significant and regulatory angle.”

In relation to getting a medical opinion from Prof. Schwartzman during the course of legal proceedings, the company responded: “We object to efforts to besmirch the integrity of an expert in a legal case, who was selected because of his professional reputation, his expertise and his years of experience. It is up to the court to decide what weight to give to his expert opinion.”

Taro also responded to Schwartzman’s professional opinion: “His membership of the committee on regulated opioid use is not relevant to the legal issue being discussed in the court.”

The Israelli Medical Association didn't send a respose.

This is a summary of shomrim's story published in Hebrew.
To read the full story click here.