In 2014, a United States Food and Drug Agency (FDA) panel acknowledged that neuropsychiatric side-effects among Singulair users were a “known safety issue,” but cited this reason and “feasibility concerns” in its decision not to order new studies, according to media investigations.

Yet, as reports of suicides continued to be filed – with 82 suicides linked to Singulair and its generic versions, including at least 31 involving people aged 19 and younger, a new FDA advisory panel was convened in 2019.

According to Reuters, “agency staffers again said there was not enough evidence” to merit this. However, with Merck’s patent having expired, an FDA official told the advisory committee that the company may opt to pull Singulair from the market rather than fund expensive new studies to investigate the product’s safety. This resulted in the March 2020 decision to add the black box label to Singulair.

In its 2020 decision, the FDA cited independent research conducted in 2015 by cell biologist Julia Marschallinger and other researchers at Austria’s Institute of Molecular Regenerative Medicine.

They found that Singulair’s distribution into the brain was more significant than what was stated on the product label, which described its brain distribution as “minimal.”

Merck had claimed, in documents it submitted to FDA for the drug’s approval in 1998, that “only a trace amount” of the drug could be found in the brain and that its presence “declined over time.” Merck’s public marketing of the product later described side-effects as “generally mild” and “similar to a sugar pill.”

However, Marschallinger’s team found that while Singulair’s presence decreased almost everywhere in the body within 24 hours after administration, the opposite was true in the brain, where “a substantial amount” of the drug was identified.

In its 1996 patent application for Singulair, Merck also claimed the drug could be used as a treatment for “cerebral spasms” – indicating “knowledge of the drug’s potential brain impacts.” Lawyers for plaintiffs filing Singulair lawsuits against Merck have cited this argument, as well as Marschallinger’s study.

The FDA has confirmed the study’s findings, acknowledging that claims regarding the declining presence of Singulair in all tissues “did not fully reflect the data.” However, according to Reuters, the FDA also characterised findings of “a substantial amount” of the drug in the brain “a subjective characterisation that is not necessarily incompatible with the ‘minimal’ descriptor in other contexts.”

“The FDA could have asked Merck to repeat the experiment or do it for an even longer period of time,” Marschallinger told Reuters. “It’s not hard to do.”

Perro said, “For those children who have been harmed by this drug,” due to the FDA’s 22-year delay in adding a black box warning, “there will not be any compensation because of pharmaceutical protection by our own government and liability shields.”

The FDA’s inaction has resulted in many deaths, Sue Peters, a CHD science fellow, told The Defender: “The FDA has placed pharmaceutical profits over the safety and mental health of our children. It’s a never-ending cycle, with increased rates of chronic illness, like asthma, leading to pharmaceutical treatments which have not been properly safety-tested.

“These drugs put young people, with critical brain myelination continuing past 25 years of age, at risk of developing mental health disorders, leading to polypharmacy with psychiatric medications, and contributing to iatrogenic deaths as a leading cause of death in the US.”

Perro calls for an overhaul of the FDA, telling The Defender: “It is clear who our government – including the judicial system – is protecting. A solution to the lack of action by regulatory agencies? Overhaul.

“In the meantime, there are safer pharmaceutical alternatives for asthma in children. Not to mention, this is yet another reason to examine the root causes as to why so many children now have asthma, and address the real culprits, such as air pollution.”

For Mumper, a new approach to treating ailments such as asthma is needed. “Although montelukast is a valuable medication in my toolbox for treating allergies, the prescription should come after other measures, including working on gut health,” she said.

Similarly, Peters called for a “careful analysis” of the role of drugs in the treatment of common disorders and their role in precipitating mental health disorders and even deaths. She told The Defender, “The tragic increase in the rate of mental health disorders in children in the United States, requires careful analysis of the role of iatrogenic death.

“Failing to consider the role of pharmaceutical drugs and medical treatments in the development of mental health disorders in children, has led to the loss of valuable research time, wasted research dollars and ultimately the loss of life. Clearly, our current system is broken.”

According to the Reuters investigative report, most of the Singulair lawsuits pending against Merck are still in their early stages.

Drugwatch reported that, as of May 16, “There have been no scheduled trials or court-approved global settlement in Singulair litigation.” Many of the suits against Merck were filed in New Jersey, where in January 2022, they were consolidated into multicounty litigation in the Superior Court of New Jersey Law Division: Atlantic County.

And in April, US District Judge Timothy S. Hillman in Massachusetts denied Merck’s motion to dismiss a Singulair lawsuit “for lack of personal jurisdiction,” Drugwatch reported. Judge Hillman argued Merck manufactured, marketed and sold the drug in the state and allowed the case to continue.

Two US Supreme Court rulings in 2011 and 2013 strengthened the pre-emption defence.

In Pliva, Inc. v. Mensing (2011), the Supreme Court held that state law requiring “generic drug manufacturers to provide adequate warning labels was preempted where federal law required manufacturers to use the same labels as their brand-name counterparts.”

And in Mutual Pharmaceutical Co. v. Bartlett (2013), the Supreme Court held that design-defect claims questioning the adequacy of a drug’s warnings under state law are pre-empted by the Federal Food, Drug, and Cosmetic Act and the Pliva v. Mensing ruling.

According to Reuters, the pre-emption doctrine rests on the US Constitution’s Supremacy Clause, which states that the Constitution and federal law take precedence over state laws and state constitutions.

As a result, “Pre-emption defences often deliver companies a swift procedural win, allowing them to avoid addressing the substance of plaintiffs’ allegations.”

While the defence has been used across multiple industries, it “has had a particularly profound impact in the pharmaceutical industry,” particularly as FDA data cited by Reuters indicates that generic drugs account for 91 per cent of US prescriptions.

Reuters, in its review of 257 US Supreme Court and federal appeals court rulings since 2001, found that “judges ruled two-thirds of the time to weaken or kill lawsuits alleging deaths or injuries caused by corporate negligence or defective products.”

Moreover, “The number of potential lawsuits that were never filed” serves as “Another industry benefit” that “can’t be quantified,” according to Reuters.

Pre-emption defences became a centrepiece of the George W. Bush administration – and FDA policy under his presidency, Reuters reports. This was part of the Bush campaign’s promise to address what it described as “frivolous” lawsuits.

Daniel Troy, the FDA’s chief counsel under the Bush administration, “interpreted pre-emption to mean that courts can’t undermine federal regulators based on alleged state-law violations,” Reuters reported, adding that he “aimed to make that argument in high-profile lawsuits” and briefed drug industry lawyers on the strategy in 2003.

Troy – who is now a pharmaceutical industry lawyer – told Reuters: “If you believe in a strong FDA, we can’t have state courts, especially juries, second-guessing and undercutting the FDA’s judgments.”

Hazlehurst says Troy’s argument is the same one used by Wyeth (Pfizer) before the Supreme Court in Bruesewitz v. Wyeth (2011). The Supreme Court’s decision in this case prohibited design defect lawsuits against vaccine manufacturers.

The US Department of Health and Human Services, the parent agency of the FDA and the Centres for Disease Control and Prevention, supported Wyeth’s 2011 argument.

Similarly, Mumper observes that pharmaceutical companies “have a history of avoiding liability through various legislative protection,” including the pre-emption defence and the National Childhood Vaccine Injury Act of 1986.

In 2006, “The FDA formally changed its view of pre-emption in a 2006 regulation, stating the agency now believed that FDA labelling approval ‘pre-empts conflicting or contrary state law,’” Reuters reported.

Hazlehurst says, “CHD is proud to have played a role in advocating and assisting these parents on the journey to hold Merck accountable,” but “one thing rings loud and clear: the FDA is a captured agency, and this is a fundamental problem.”

Some parents have questioned whether the black box warning for Singulair was enough to save lives, citing the damage already done, continued legal obstacles, and Merck’s strong marketing campaign for the drug.

“Due to tremendous financial conflicts of interest, the pharmaceutical industry has tremendous influence over the FDA,” Hazlehurst said. “As a result, the FDA protects the pharmaceutical industry first and people second – this story is just one example.

He added: “One must wonder, how many lives could have been spared if the FDA had timely done its job of properly investigating and regulating the pharmaceutical industry?”

• The Defender report / By Dr Michael Nevradakis