Nicholas England, a healthy 22-year-old from Virginia, shot himself in the head in 2017, less than two weeks after he started taking an allergy medicine that had been linked for years to episodes of depression and suicidal thinking.

His parents soon started exploring a lawsuit against Merck, the developer of the blockbuster asthma and allergy drug, Singulair, along with the manufacturer of the generic version their son took. Nicholas had no history of mental-health problems, they said.

The Englands were shocked to learn from legal advisers that they had no case. Like countless other potential plaintiffs, they had run into one of Corporate America’s most effective liability shields: the legal doctrine of preemption, the principle that federal law supersedes state law.

Armed with U.S. Supreme Court rulings on preemption starting in the 1990s, companies increasingly argue that federally regulated products or services should be immune from lawsuits alleging state-law violations. In a new reading of an old constitutional principle, judges have held that federal law, including the decisions of U.S. regulatory agencies, should preempt, or override, state statutes that seek to hold companies accountable for harming consumers.

State laws historically have provided the legal basis for some of the most common lawsuits against U.S. companies alleging injuries, deaths or illnesses caused by negligence or defective products.

These legal dynamics left the England family with no legal remedy at all. A pair of U.S. Supreme Court rulings, in 2011 and 2013, essentially barred lawsuits against generic drugmakers based on state laws that enabled claims over design defects or a failure to warn consumers of potential dangers. The court’s reasoning: Such claims were preempted by federal regulations preventing generic drugmakers, when copying name-brand drugs, from changing the formulation or the warning label.

That meant Merck had written the warning label, with federal approval, on the generic version of Singulair that Nicholas England took. But his parents couldn’t sue Merck, either, because their son had never taken its name-brand version of Singulair.

“The emotion of losing your child is so difficult on its own,” said Jennifer England, Nicholas’s mother. “It is very frustrating to realize that’s a loophole. I’m a small person in southwestern Virginia, and that’s a loophole there to protect companies much bigger than we could fight.”

Merck declined to comment for this report, referring all questions to Organon, a Merck spinoff created in 2021 that now markets Singulair. Organon declined to answer detailed questions from Reuters but said in a statement that it’s confident doctors and patients have gotten “complete and appropriate information” on Singulair’s safety. The generic drug manufacturer that made the pills England took, Teva Pharmaceuticals, did not respond to inquiries.

Corporate preemption defenses have proved broadly effective, according to a Reuters analysis of court cases and dozens of interviews with attorneys, legal scholars and plaintiffs or potential plaintiffs affected by preemption rulings. The analysis of federal appeals and Supreme Court rulings involving preemption 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.

Preemption defenses often deliver companies a swift procedural win, allowing them to avoid addressing the substance of plaintiffs’ allegations. It has been used across a range of federally regulated sectors, from railroads to agricultural chemicals to airlines and automobiles, the Reuters review found.

The preemption defense has had a particularly profound impact in the pharmaceutical industry, the review showed. The high court’s ban on certain lawsuits against generic drug manufacturers has extraordinary reach because generics account for 91% of U.S. prescriptions, according to data from the U.S. Food and Drug Administration (FDA).

Name-brand drugmakers can still be sued, but preemption defenses can make it much harder for plaintiffs to prevail, drug-industry litigation experts said. In many product-liability cases, plaintiffs must prove simply that a company’s product was unsafe. Those facing drugmakers’ preemption defenses must often demonstrate that a company failed to disclose safety information to federal regulators – and that the information could have spurred new government restrictions or warnings before the alleged harm occurred.

Pending lawsuits against Merck allege that the company’s own early research indicated the drug could impact the brain but that Merck downplayed any risks in statements to regulators.

England’s family had hoped to force executives from Merck and the generic manufacturer to reveal what they knew, and when, about the drug’s dangers. In the decade before England’s death, the FDA received more than 4,800 reports of patients, including many children, experiencing depression, suicidal thoughts or other psychiatric problems after taking Singulair or a generic version, according to a Reuters review of FDA data.

But it wasn’t until 2020 that the FDA slapped its most serious warning, called a “black box,” on the drug’s label. By that time, the FDA had received more than 80 reports of suicides in people taking the medicine.

Singulair, one of the best-selling drugs in U.S. history, has provided Merck with about $50 billion in revenue, company disclosures show. Since Merck’s patent on Singulair expired in 2012, major generic drug manufacturers have sold millions of prescriptions under the drug’s scientific name, montelukast.

The FDA said in a statement that it has “diligently monitored reports of side effects possibly associated with montelukast, as well as communicated findings and taken regulatory action, when appropriate.” The agency said it “continues to monitor and investigate this important issue.”

The FDA declined to comment on how modern preemption defenses and court rulings have impacted pharmaceutical regulation and litigation.

BIG TOBACCO PRECEDENT

The doctrine of preemption is based on the U.S. Constitution’s supremacy clause. The original intent: to resolve conflicts between federal and state statutes and discourage state legislatures from passing laws that undermine federal policy.

Preemption-based corporate defenses are a modern phenomenon. American courts have historically viewed product-liability lawsuits, largely based on state laws, as vital to holding companies accountable when federal laws and regulations fail to do so. Courts recognized drugmaker liability for harmful medicines as early as the 1850s, according to a Supreme Court filing. FDA regulations once routinely specified that its decisions had no impact on drugmakers’ liability.

That started to change in 1992, in a case involving a smoker who died of cancer. The Supreme Court ruled that federal requirements for cigarette labels, which had included smoking warnings since the 1960s, overrode some of her family’s state-law claims that a tobacco company failed to warn her about smoking hazards.

States ultimately used different theories to force Big Tobacco into a $246 billion settlement. Still, the precedent gave Corporate America a blueprint for defeating similar lawsuits on preemption grounds.

Corporations got more help in the political arena. U.S. President George W. Bush had promised in his 2000 campaign to attack what Republicans derided as frivolous litigation targeting American industry. Administration officials undertook what critics dubbed “stealth” tort reform: intervening in lawsuits on the side of corporate defendants, with the goal of convincing judges to set precedents making it harder to sue companies.

Bush’s FDA exemplified the tactic. Daniel Troy, the agency’s chief counsel, interpreted preemption to mean that courts can’t undermine federal regulators based on alleged state-law violations. He aimed to make that argument in high-profile lawsuits. At a 2003 conference, Troy invited an audience of drug-industry lawyers to pitch the FDA on intervening in their cases.

“We can’t afford to get involved in every case – we have to pick our shots,” he told the assembled lawyers. “So make it sound like a Hollywood pitch.”

Troy, now a veteran pharmaceutical industry lawyer himself, said his goal at the time was simply to defend and strengthen the FDA’s authority to regulate without interference.

“If you believe in a strong FDA,” he said, “we can’t have state courts, especially juries, second-guessing and undercutting the FDA’s judgments.”

The FDA formally changed its view of preemption in a 2006 regulation, stating the agency now believed that FDA labeling approval “preempts conflicting or contrary State law.”

In its statement to Reuters, the FDA declined to comment on the 2006 regulation or the agency’s current view of preemption.

One of the Bush-era FDA’s biggest victories came in 2008, when the Supreme Court cited preemption in dismissing a New York man’s lawsuit against Medtronic over a burst balloon catheter. The precedent has since effectively barred wide swaths of lawsuits against medical-device manufacturers.

To examine the impact of preemption defenses, Reuters reviewed 257 federal appeals and Supreme Court rulings, which are the most influential in establishing precedents. In the cases, dating back to 2001, the courts determined whether preemption nullified plaintiffs’ claims that deaths or injuries were caused by corporate negligence or defective products. Judges threw out some or all of the claims on preemption grounds in two-thirds of the cases.

Another industry benefit can’t be quantified: The number of potential lawsuits that were never filed – like the one over Nicholas England’s death – because preemption precedents favor corporations, legal experts said.

Adam Zimmerman, a professor at the University of Southern California’s Gould School of Law, said the Reuters analysis underscores how these preemption precedents, which bind lower courts, have delivered corporations critical courtroom wins and leverage in settlement negotiations.

“It is really meaningful for the business community,” Zimmerman said.

Jay Lefkowitz, a Kirkland & Ellis partner who has represented companies before the Supreme Court, called preemption a “firmly enshrined” constitutional principle. State court juries, he said, shouldn’t be deciding how drug labels read based on the evidence in one case.

“We want the scientists and doctors at the FDA to do so,” he said, “based on all of the accumulated data from clinical trials and real world experience.”

TRAIN WRECK

Corporate preemption defenses are now common across a host of federally regulated industries.

After a February train derailment in East Palestine, Ohio, released toxic chemicals, train operator Norfolk Southern invoked preemption to counter pending lawsuits.

Asked about the legal strategy, the company told Reuters it was “following the legal process” and that it was committed to paying for the environmental clean-up and any damage to residents’ health, water supply or property values.

The Reuters analysis found about three dozen examples over the past two decades of companies in the railroad industry invoking preemption to avoid liability. They cite federal laws regulating the safety of railroads and hazardous materials transportation. In 2015, for instance, a Union Pacific train struck a pickup in Louisiana, killing three people, according to court records. The truck’s driver was the last in a convoy, waiting to proceed through a gate that hadn’t yet opened. Seconds later, a Union Pacific train barreled down the tracks at about 50 miles an hour.

The crash victims’ families sued and lost, in part because the Federal Railroad Safety Act preempted their claims that a horn sounded by the conductor failed to adequately warn of the oncoming train. Plaintiffs had argued that several short horn blasts, for instance, would have been more effective. An appeals court ruled their case was preempted because federal regulation defers to an engineer’s “sole judgment” on sounding a horn in such instances.

Union Pacific said in a statement that the engineer complied with federal law and that preemption provides a “consistent, uniform law” for train operators transporting goods across state lines.

In another pharmaceutical case involving suicide, a woman whose husband threw himself in front of a train shortly after he started taking the antidepressant paroxetine was barred by preemption from suing the generic manufacturer. Then, an appeals court cited preemption in overturning a $3 million verdict the woman had won against GlaxoSmithKline, which made the brand-name version of the drug and controlled its label. The court found that the FDA would have rejected an adult suicide warning at the time her husband took it.

GlaxoSmithKline said in a statement that preemption is a “well-established legal principle grounded in the U.S. Constitution” to address conflicts between federal and state law. The company said it repeatedly asked the FDA to add a warning about suicidal thinking in adults to the label but the agency refused. The FDA instead mandated the same label for all drugs in the class that included paroxetine, which did not include such a warning.

Agricultural giant Monsanto is now pinning its hopes on preemption to help defeat or weaken tens of thousands of legal claims alleging it failed to warn consumers that its popular weed killer Roundup could cause cancer. In June, the company, owned by Bayer, urged a federal appeals court in Atlanta to dismiss one of those cases on preemption grounds, arguing federal regulators did not require a cancer warning on Roundup’s label.

Bayer said in a statement that these state-based claims are preempted because federal law expressly forbids states from instituting different labeling requirements. Federal regulators, Bayer said, have consistently found that Roundup and similar herbicides can be used safely and are not carcinogenic.

While preemption precedents favor corporations, judges’ tolerance for the argument has its limits. The Supreme Court in 2009 rejected the contention from drugmaker Wyeth, along with industry groups, that FDA approval should give name-brand drugmakers blanket immunity from certain types of lawsuits. The court ruled in favor of a Vermont woman who alleged the firm’s drug Phenegran led to the amputation of her arm.

'I WAS POISONING HIM'

Preemption defenses rely in part on the notion that state laws are not needed to protect citizens who are already safeguarded by federal regulators. But in the case of Singulair’s potentially deadly side effects, the FDA waited years, despite thousands of reported psychiatric problems, to require its most serious warning on the drug’s label.

By the time Nicholas England killed himself, the FDA had been reviewing Merck’s disclosures about health risks for nearly two decades. Parents who argue Singulair endangered their children view the FDA’s 2020 decision to add a black box warning as vindication, but many still want to sue Merck for not acting sooner.

In the years after Singulair’s 1998 launch, reports of related neuropsychiatric episodes piled up on internet forums and in the FDA’s early-warning detection system. The system compiles reports of “adverse events” from patients, doctors and others to track potential dangers discovered after a drug hits the market.

Jan Gilpin’s son was first prescribed Singulair for asthma in 2003, at age three. The boy soon seemed withdrawn and sullen. He would sometimes go “into a strange trance, mumbling to himself,” Gilpin wrote in 2008 in a report to the FDA. “Worst of all, he started talking about death – wanting to die, wishing he was dead, saying that he hated himself.”

Gilpin didn’t suspect Singulair for more than three years. In 2007, she stopped giving her son the drug after she stumbled on parents’ online posts about their children experiencing social anxiety while taking the medicine.

Soon, she noticed he began to skip and laugh.

“I realized he hadn’t laughed in two years,” said Gilpin, speaking through tears. “I didn’t realize that I was poisoning him with this medicine.”

The boy’s obsessive thoughts about death disappeared after he quit the medicine, Gilpin said, but he seemed to have some lingering effects, such as anxiety, that took longer to go away.

In August 2007, a 15-year-old boy in New York killed himself 17 days after first taking Singulair. Two months later, Merck proposed, and the FDA agreed, to amend Singulair’s label to add suicidal thinking and behavior to a list of adverse events reported to the company.

But the mention of suicidal thinking appeared in the middle of a list of more than three dozen side effects. Parent advocates argue the new label was grossly inadequate to warn of such a grave risk.

Three weeks after proposing the label change, Merck asked the FDA about getting permission to sell Singulair over-the-counter, without a prescription, for adults with hay fever. The FDA agreed to consider it but also wanted to understand more about suicide risks. A 2008 FDA review of the drug’s psychiatric affects and suicide risks recommended “further studies in animals and humans” and suggested the agency consider asking Merck to conduct an observational study.

The FDA did not require such a study, reasoning in part that serious side effects including suicidal thinking “were expected to be quite rare.”

In 2011, the agency rejected a petition from Gilpin and other parents seeking a black box warning, citing what it called insufficient evidence that the drug caused suicidal behavior.

82 SUICIDES

After Merck’s patent on Singulair expired in 2012, generic manufacturers started producing the drug. The number of patients prescribed the medicine climbed from about 7 million annually to more than 9 million, according to the FDA. Some years, nearly half of these patients were 16 or younger.

The FDA convened an advisory panel in 2014 to consider Merck’s request to offer Singulair over-the-counter. At the FDA’s request, Merck had re-analyzed its Singulair clinical-trial data in 2009. The company had reported that an 18-year-old trial participant had attempted suicide and a 12-year-old was hospitalized for depression and suicidal thoughts. In both cases, the trial investigator determined the events were not related to Singulair. In 2014, Stephane Bissonnette, a Merck manager at the time, told the FDA panel that “suicidality was quite rare” in the trials.

The FDA also analyzed Merck’s data and generally agreed with its conclusion, though the agency acknowledged the trials were short and not designed to detect neuropsychiatric effects.

The FDA panel recommended rejecting the request to sell Singulair over-the-counter because of safety concerns. The panel also called for new studies on its neuropsychiatric side effects, a patient registry, and an assessment of how well patients understood Singulair’s label.

Reports of neuropsychiatric side effects “really should give us pause that there may be something there we don’t understand,” Dr. Judith Kramer, Duke medical professor and an advisory committee member, said at the 2014 meeting.

The FDA followed only half the recommendation: It declined to authorize over-the-counter sales but also refused to order new studies, in part because neuropsychiatric side effects were already a “known safety issue,” an agency safety official said at the time.

The FDA told Reuters it declined to order more research because of “feasibility concerns.”

In 2019, the FDA convened another advisory panel on whether the drug’s side effects merited a black box warning. Before the meeting, the FDA tallied 82 suicides linked to Singulair and its generic versions reported to its adverse-event database since 1998. Only 64 of the reports provided an age; of those, 31 involved someone 19 or younger.

Still, agency staffers again said there was not enough evidence to merit a black box warning, noting that the label already warned of potential neuropsychiatric events.

FDA staff acknowledged the agency had the authority to require new studies. But Merck now had little incentive to conduct expensive research because its patent on Singulair had expired and its profits on the drug had plummeted. Instead, Merck might just pull Singulair off the market, an FDA official told the advisory committee in 2019.

Instead of requiring new studies, the FDA announced in March 2020 that it would add a black box to the labels of Singulair and its generic variations, warning of serious neuropsychiatric side effects including suicidal thinking and behavior. The agency cited independent research from 2015 showing the drug’s distribution in the brain. The FDA advised restricting use of the drug for treating allergies, saying it should not be the first-choice treatment.

"THIS DOES NOT MAKE SENSE'

Reuters interviewed 16 patients or their parents who suspect that Singulair caused psychiatric side effects. Many, like Nicholas England, took a generic version.

England grew up in the rural town of Wise, Virginia. He was easygoing and physically fit, and would refuse junk food when the rest of the family was having it, said his father, Robert England. He believed his son may have struggled to sleep after taking the drug, but otherwise seemed normal.

After Nicholas died, a police report noted that he didn’t have illicit drugs in his system. The case puzzled sheriff’s investigators, Robert said: “All these guys looked at me and said, ‘This does not make sense.’”

In the years when the FDA delayed action on Singulair, some parents began contacting lawyers to explore taking legal action. Most, like the Englands, were barred by court precedents from suing because their children took a generic version of the drug. Kim Beck, an attorney who eventually filed hundreds of lawsuits against Merck over Singulair, said her firm turned away thousands more potential clients who had taken generics.

The FDA’s 2020 regulatory action encouraged some patients to sue Merck. Most of those lawsuits are in early stages, but Merck has had some success with preemption defenses.

In Wisconsin, for instance, a mother sued Merck in 2020 claiming Singulair caused her son to be institutionalized with severe depression. The boy was prescribed Singulair in 2010, but switched to the generic version in 2012.

Merck argued the plaintiff couldn’t show the FDA would have approved a stronger warning before 2012, when the boy was taking brand-name Singulair. The drugmaker cited the agency’s 2011 rejection of the petition by Gilpin and other parents to add such a warning.

A judge agreed, ruling that “the relevant federal and state laws in this case irreconcilably conflict.” He dismissed nearly every claim in the lawsuit, which the mother then dropped.

MERCK ACCUSED OF DOWNPLAYING EARLY EVIDENCE OF DRUG'S BRAIN IMPACT

An early magazine advertisement for Merck’s breakthrough asthma and allergy medicine, Singulair, featured a happy child, hanging upside-down from a tree. Asthmatic kids could now breathe easier, the text assured, and side effects were “usually mild” and “similar to a sugar pill.”

When the drug launched in 1998, its label said the drug’s distribution in the brain was “minimal,” with no mention of psychiatric side effects.

Merck’s early safety claims later faced intense scrutiny amid reports over two decades that patients, including many children, had died by suicide or experienced neuropsychiatric problems after taking the drug. The FDA in 2020 ordered its most serious warning, known as a “black box,” on Singulair’s label. And Merck now faces a raft of lawsuits alleging it knew from its early research that the drug could impact the brain and that it minimized the potential for psychiatric problems in statements to regulators.

The lawsuits cite the research of Julia Marschallinger, a cell biologist who has studied the drug along with colleagues at the Institute of Molecular Regenerative Medicine in Austria. That team found in 2015 that the drug’s distribution into the brain was more significant than its label described. The FDA cited Marschallinger’s work when it ordered Singulair’s black-box warning label.

In its original patent for Singulair, Merck cited other applications for the drug, beyond asthma and allergies, including as a treatment for “cerebral spasm,” a neurological condition. Lawsuits filed against Merck cite this 1996 patent as evidence of Merck’s knowledge of the drug’s potential brain impacts.

Merck declined to comment for this report.

When Merck first sought FDA approval for Singulair, an FDA analyst, relying on company assertions, said in 1998 that “only a trace amount” of the drug could be found in the brain, federal documents show. The FDA said Merck’s data showed the presence of the Singulair “declined over time” in all tissues.

Marschallinger and her colleagues in Austria came away with a different finding when they reviewed Merck’s original research and did some of their own. They started looking at Singulair as a potential dementia treatment in 2011. They became interested in that prospect in part because of the reports of psychiatric side effects, such as depression, agitation or hallucinations, from patients and medical providers. While troubling, the side effects showed the drug might affect the brain. The researchers wanted to understand if it could benefit older patients with dementia.

In 2014, the scientists in Austria reanalyzed Merck’s original animal studies and noticed the drug decreased almost everywhere in the body 24 hours after dosage – but not in the brain, where it increased over this period, surpassing the amount in both the blood and the lungs. She reported finding a “substantial amount” of the drug had reached the brain, in contrast to Merck’s description of the brain distribution as “minimal.”

The FDA said Merck’s original animal studies were “quite limited and cannot provide any definitive information about the montelukast levels and activity in the brain.” The agency acknowledged that its reviewer’s description that drug levels declined over time in all tissues “did not fully reflect the data.”

As for Marschallinger’s finding that a “substantial amount” of the drug had reached the brain, the FDA called it “a subjective characterization that is not necessarily incompatible with the ‘minimal’ descriptor in other contexts.” The researchers’ 2015 study, the FDA said, provided additional evidence that the drug reached the brain but did not show any specific harm.

Marschallinger said it would have been logical for the FDA to require Merck to investigate the brain impacts more thoroughly once reports of mental-health problems emerged.

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