'Sheriff' Cardiologist Sounds the Alarm on Ineffective Generics

James F. Sweeney

October 28, 2019

CLEVELAND ― Harry Lever, MD, doesn't look like a crusader.

The 74-year-old cardiologist slumps in the chair in his office at the Cleveland Clinic, sleeves rolled up and glasses on top of a head of gray hair. The office is comfortably cluttered, with pictures of family, files, and other papers. An inscribed Louisville Slugger, a gift from grateful patients, is mounted on the wall.

But when he gets started on the subject of harmful generic drugs, his voice rises along with his indignation.

"Look at this," he says, getting to his feet and opening a cabinet to reveal a row of prescription bottles. "This is medicine I've taken from patients because I didn't think it worked."

Lever, who is director of the Clinic's Hypertrophic Cardiomyopathy Center, was one of the first in this country to raise the alarm about ineffective and even harmful generic drugs, largely imported from India and China.

"I wish it was more commonly known. Everybody thinks everything is OK, but it's not," he said. "We're treating sick people. It's important this stuff works."

Dr Harry Lever, director of the Cleveland Clinic's Hypertrophic Cardiomyopathy Center, wrote to the US Food and Drug Administration about his concerns that generic versions of Toprol XL were ineffective. Some versions were later recalled. Source: Cleveland Clinic

It's not been an easy fight. Generic drugs have been a blessing for millions of patients, insured and uninsured alike, because of their relative affordability. Doctors like them; patients like them; and insurance companies like them to the point of usually insisting upon them when they're available.

Raising warnings that some generics do patients more harm than good is problematic, even unwelcome. Lever doesn't care.

"We've got to worry about sick people. We can't just worry about money," he said. 

Lever's crusade began in 2007 on a morning commute to the Clinic when he heard an NPR report about contaminated food and drugs imported from China. He ordered the transcript of the story, then began checking the origins of the generic drugs he'd been prescribing patients.

He found that many drugs or their active ingredients were being made in China or India for American drug manufacturers. Generic versions of one beta-blocker in particular, metoprolol (Toprol XL), concerned him.

For years, his patients who'd switched from the brand name Toprol XL to a generic version had complained about chest pains and other symptoms. When Lever put them back on the brand drug, the symptoms disappeared.

He wrote the Food and Drug Administration in 2012 about his concerns and traveled to Washington in 2014 to raise the alarm. He was proven right that year when two Indian manufacturers recalled their versions of the beta-blocker because the pills were not dissolving properly.

"I felt vindicated because I called it right," he said. "I recognized it was a problem and I called it."

He has not let up. He researches generics, where they are manufactured, where their ingredients come from, and the results of FDA inspections of foreign factories. And he has continued to amass anecdotal information from his own practice about patients who did poorly with foreign-made generics, then improved when they were switched to brand names or domestic generics. 

"I didn't have any data; I just had observations," he said. "It became my hobby, I guess. The more we looked, the more we found."

What he's discovered is that the FDA does not do enough, in his view, to inspect foreign manufacturers and that domestic drugmakers fight efforts to make public the origins of their ingredients.

"If I go to the fish market, I know where my fish is coming from because it's all labeled," Lever said. "I know where my salmon is coming from, but I can't know where my drugs are coming from. The FDA says it's confidential information. It should not be confidential information, not at all. That's wrong."

He's a zealot on this and a sheriff, and I've been deputized. Randall Starling, MD, Dr Lever's colleague at Cleveland Clinic

The medical community is beginning to pay attention to the danger. A 2019 book, Bottle of Lies: The Inside Story of the Generic Drug Boom by investigative journalist Katherine Eban, has been getting widespread attention.

Lever was a source for Eban in her reporting and she credits him with leading the fight against dangerous generic drugs.

"Dr Lever has been tireless in raising the alarm publicly, and with the FDA, about those generics that he felt were actively harming his patients," she wrote in an email. "And remarkably, in case after case, he has been correct in his clinical judgments, and often far ahead of the FDA in detecting problematic drugs. His patients, many of whom I interviewed for Bottle of Lies, are grateful to him, as we all should be."

In January, Bloomberg published the results of a year-long investigation that found widespread problems with the consistency and quality of generics and the FDA supervision of manufacturing, particularly overseas, where the number of factories it inspects has been on the decline. Lever is infuriated that life-saving drugs aren't subject to the same oversight as, say, a bottle of ketchup.

"Have you ever had a bad bottle of Heinz ketchup?" he asked. "No. We need to test the drugs more. Every batch needs to be tested. We've got to know about these active ingredients — who's making them under what conditions? All factories have to submit to inspections without knowing they're coming."

Lever has been busy spreading the word at the Clinic, said colleague Randall Starling, MD, MPH, and past president of the Heart Failure Society of America.

"He's a zealot on this and a sheriff, and I've been deputized," said Starling, who thanks Lever for opening his eyes to the problem. Now, like Lever, he routinely checks the origins of generic medications.

"Five years ago, it never entered my thought process. Now, it consistently enters my thought process," he said. "I really credit Dr Lever for informing my own personal behavior."      

The uncertainty over generics has given physicians an unwelcome complication to the problem of solving why a patient does not respond to a medication. Is it the wrong medication, or is there something wrong with the medication?

"There used to be one unknown — the patient," said Lever. "Now, I've got two unknowns; I've got the patient and I've got the drug. And it can be very difficult sometimes. I'm sitting in my office trying to take care of people and I don't know if I've got some inconsistent batches or if they're making mistakes making it or what."  

Despite all his misgivings, Lever still prescribes generic drugs. Brand name drugs are simply too expensive, or patients' insurers will cover only generics. However, he does try to specify that the generics come from American companies that manufacture in this country under the eye of the FDA. 

"If we have an American company at least I have a feeling they're going to test it, and if it's not right, they're going to do something about it," he said.

He's fully aware of the long odds facing his crusade, but, as a doctor, he owes it to his patients.

"Who's responsible for them?" he asked. "Me! If it doesn't go good, it's my problem."

James F. Sweeney is a freelance writer in Cleveland, Ohio.

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