The opioid crisis is an epidemic characterized by the misuse and abuse of opioid drugs used to alleviate excruciating pain. This is most prominent in the North American Market, especially in the US and Canada. Starting from 1999, many deaths have been linked to the crisis. Current estimates put that number to an excess of 600,000. It is suggested that in the next five years, we may face another 1.2 million deaths due to opioid overdose. The number of people suffering from opioid addiction is far more. For example, in 2017 alone, about 2.4 million inhabitants of the US were suffering from it. 

US policymakers formed the Stanford-Lancet Commission to study the opioid crisis and make recommendations. Professor Howard Koh of Harvard T.H. Chan School of Public Health was a commission member. He labeled the opioid crisis as a devastating public health emergency. The starting point was in 1999 with the introduction of Oxycontin by Purdue Pharma. It soon followed with deaths related to legal prescriptions of the drug, the so-called ‘first wave.’ The second wave occurred in 2010. But it was the third wave that we are talking about now. It commenced in 2013 as the markets were flooded with several synthetic opioids, including Fentanyl. 2020 was the deadliest, claiming almost 76000 lives in the US and 6200 in Canada. This was an increase of 30% and 67%, respectively, compared to 2019. 

But why are so many deaths in countries generally viewed as having a strong and effective regulatory agency? It was later revealed that there were many intentional or unintentional lapses, which is cause for debate. However, those lapses, coupled with the reluctance of the pharma industry to be fully compliant with regulation and seeking loopholes to maximize profits, snowballed the crisis. 

For example, it was later revealed that the US Food and Drug Administration (FDA) and Health Canada (HC) failed to ensure proper labels on the drug packages, an essential source of information for physicians and patients alike. They also ignored the early warnings issues by health care experts. This has been attributed to prioritizing pharma industry interests over public health concerns. 

The reason for this is obvious. Pharma companies play an important role in determining regulatory policies and implementations. This is because big players influence decision-making through donations to advocacy groups, political campaigns, and medical programs. It is not uncommon to see renowned universities receiving big money from pharma for physician education and training programs. Those companies also contract many third parties operating in the health education sector. 

Drug manufacturers wield some influence on curriculum development. These companies conduct education campaigns for new drugs, making it easy to present only favorable information to stakeholders, e.g., doctors and patients. 

Patrick Keefe, an investigative journalist, aptly said in his book ‘Empire of Pain’ that the opioid crisis is just a testament to how pharma companies undermined public institutions. Purdue Pharma, which has been implicated and later fined in the opioid crisis, is a clear example. When they submitted Oxycontin for regulatory approval, they used misleading evidence to reduce the addiction potential of the drug, making it a weak opioid, while in reality, it was not. Their goal was to maximize the customer base, thus driving profits. Patient concern was not the basis of their decision, though it should have been from legal, ethical, and compliance perspectives.  

We should also not overlook drug promotional practices. Pharma companies regularly roll out education and information programs. Even though there are frameworks for those, compliance is not a hundred percent. The program materials and target groups are often subtly influenced by the manufacturers. They identify key opinion leaders (KOLs), who are essentially well-known physicians with the capability to influence the prescription practices of others. The objective is to bring a few KOLs into the fold, thus generating more prescriptions and sales. 

Providing gifts and financial incentives directly to physicians is also not uncommon. There are strict industry codes governing the relationship between physicians and pharma companies. However, many manufacturers do not comply with the code as they should. It was found that one out of seven US doctors received gifts from opioid-linked gift manufacturers between 2014-2015. 

Boston University School of Medicine researchers led a study that showed that aggressive marketing practices drive prescription and also deaths from overdose. The thrust of the promotion was to expand the customer pool from cancer pain to chronic non-malignant pain while downplaying the addiction, abuse, and misuse potential. Other companies employed similar strategies in the international market. Technology was also leveraged. Purdue Pharma financed technology companies to generate electronic prompts to encourage prescribing opioids. These prompts came up when the physicians were using Electronic Health Record software.

Lax regulatory enforcement was a contributing factor to the opioid crisis. Oxycontin, when first introduced, had limited information in its product monograph. A monograph is a key source of information for physicians. The monograph must be updated as more information comes from research and market data. The initial monograph approved by the FDA and HC identified drug abuse as not a problem as long as the drug is properly indicated. However, market data belied this statement, causing the FDA to update the label in 2001. HC took another five years to do the same. But the damage was done. 

Pharma company’s involvement in physician education was another factor in exacerbating the opioid crisis. According to the regulatory guidelines, their involvement should only be limited to funding, not the content and delivery. Many opioid manufacturers deviate from that. Purdue donated a large sum to the Tufts University in Boston. In 2014, some of their opioid-related materials were approved for teaching. A book titled ‘Dreamland’ by Sam Quinone was also later removed from references suggested by Tufts University School of Medicine. That book criticized Purdue for the opioid crisis. 

Attorney-General of Massachusetts made thousands of material public in 2019. All related to the investigation of Purdue’s potential malpractice in promoting opioids. Those showed how deeply that company was involved in academic and regulatory institutes, potentially allowing them to affect decisions and enforcements. Many company executives were appointed to the advisory councils and faculty teams, creating a potential conflict of interest. 

Patient Advocacy Organisations (PAOs), which should be fighting for patient rights, were also penetrated. A US Senate report demonstrated several opioid companies funding fourteen PAOs 9 million USD in 2012-17. US Pain Foundation alone got $2.9 million. Political lobbying was also deemed to be a lucrative area of investment. Starting in 2006, opioid companies spent $880 million on such activities, as described by the Center for Public Integrity (CPI) and the Associated Press. 

From what we have seen, it is clear that the burden of the opioid crisis falls on two factors- lack of compliance on the part of the manufacturer and failure to enforce regulations by the authority. Ideally, every pharma company should have an ethics and compliance officer. All big pharma companies have it. There is also an industry code. Each activity, be it promotional or non-promotional, must be cleared based on the code, and only after that it should be rolled out. Any discrepancy must be handled transparently and rectified appropriately. This is the standard practice. However, this was not followed by many opioid manufacturers, and here, the role of regulatory agencies becomes important.

The regulatory agency must have a mechanism to ensure any new drug is thoroughly vetted and information is regularly updated as it becomes available. Both FDA and HC have it, but the enforcement of the system left much to be desired. Going forward, regulators are committing to more resources in this. 

A recommendation that came out of the opioid crisis is to make a drastic change to the regulatory framework. At this moment, regulatory agencies are closely connected to pharma and government in terms of decision-making. The idea is to make it completely independent. Members would be carefully screened for any conflict of interest. The agency funding should not be controlled directly by the government. 

Pre-clearance of materials delivered to the doctors is also critical. Right now, it is the prerogative of the pharma companies. They have a system to review it according to the existing regulations. The Pharmaceutical Advertising Advisory Board (PAAB) independently verifies the content in Canada. However, PAAB is funded by pharma, and its code is very relaxed. Due to the opioid crisis, steps have been taken to strengthen the code. But, more needs to be done to ensure independent decision-making. 

So, what the future holds for us? In the coming years, there will be more focus on the relationship between pharma companies and doctors and the authorities’ enforcement of regulations and industry codes. To comply with changing realities, manufacturers must invest more to ensure compliance with applicable practices. The ethics and Compliance office must be empowered more, allowing them to make a difference. Conversely, regulators must adapt to the rapidly changing pharma landscape and employ proper safeguards to ensure compliance. This not only applies to North America or the opioid companies but to everyone. 

Dr. Imtiaz Ahmed graduated from Dhaka Medical College and currently resides in Canada. He has over seven years of experience in healthcare compliance. At present, he is working with patient support programs, as well as supporting auditors and external regulators to ensure alignment with applicable laws and procedures. He was part of the internal team that investigated opioid crisis-related issues at the company and coordinated with external stakeholders. He is also a published writer of historical non-fiction and fiction books. His most recent works include a two-book series on England and France’s Hundred Years War and a biography of a book series on renowned admirals, both published in Ekushey Book Fair 2024. 

imtiazdmc@gmail.com