(InvestigateTV) - The Food and Drug Administration knew for years that rogue doctors were wrongly prescribing the most potent opioids on the market by subverting the agency’s oversight program.
Yet the FDA accepted the word of pharmaceutical companies administering the program that they were properly policing the doctors. But they weren’t, and patients died.
Nearly 5,000 documents, obtained by InvestigateTV through a Freedom of Information Act request to the FDA, paint a picture of lax oversight and missed opportunities to clamp down on the fentanyl prescription abuses.
The records show the FDA knew the dangerous drugs intended only for cancer patients who were already taking opioids were also prescribed by the doctors for non-cancer patients.
The FDA ceded virtually all control of the oversight program to the drugmakers of transmucosal immediate-release fentanyl (TIRF) opioids that are as much as 100 times stronger than morphine.
The drugmakers, in turn, failed to ban doctors with repeated violations from prescribing the drugs, the records show. Even the FDA noted in 2016, the industry group’s policy was unclear on what actions would lead to suspension or removal. One doctor continued in the program even after he was indicted by a federal grand jury for healthcare fraud and distributing controlled substances.
The oversight program, known as Transmucosal Immediate Release Fentanyl-Risk Evaluation and Mitigation Strategy or TIRF-REMS, was created by the FDA in 2012 to add an extra level of safety protection to fentanyl drugs because of the high risk of abuse, misuse and overdose.
Doctors are required to take an 11-question-test about the restricted use of TIRF drugs; patients have to sign a form stating that they understand the risks associated with the drugs and that they were intended only for patients taking opioids round-the-clock for at least a week.
In May, InvestigateTV revealed how the FDA handed over control of the program to drug distributor McKesson Corp. and pharmaceutical companies that manufacture fentanyl products. Under the companies’ watch, TIRF prescriptions were given to non-cancer patients who weren’t opioid tolerant. While not illegal, these prescriptions to unqualified patients goes against the intentions of the regulatory program.
Representatives from McKesson, FDA and TIRF-REMS drug makers declined interview requests. “We are confident that McKesson fulfills its role as a third-party service provider for the TIRF-REMS program in an independent and professional manner,” a McKesson representative wrote in an email.
Documents and interviews show the FDA set up the program to take a hands-off regulatory approach, relying instead on the drugmakers to enforce the protocols of the oversight program.
The lax enforcement had consequences: the majority of patients prescribed the potent subdrugs didn’t qualify and some of them died. The drugmakers prospered from sales of the high-priced drugs.
“I really don't know how Big Pharma got involved in managing a program that is designed to basically control Big Pharma,” said Bill Renton, a former agent with the U.S. Drug Enforcement Agency.
Stephanie Lopez had a litany of serious health ailments: traumatic brain injury, chronic obstructive pulmonary disorder, sleep apnea and complex regional pain syndrome.
What she didn’t have was cancer.
Even so, a Saginaw, Michigan, doctor prescribed her one of the most potent TIRF drugs on the market – the fentanyl spray Subsys.
Dr. Gavin Awerbuch began prescribing Subsys to his patients almost as soon as it hit the market in 2012. The drug industry overseers, who were supposed to watch for abuses among prescribers, knew he was a problem by March of 2013, FDA records show.
That month Awerbuch failed to file the required paperwork for 62 patients, meaning those people received fast-acting fentanyl without the signed agreement forms stating they understood the risks.
TIRF-REMS safety protocols require a warning letter if a doctor fails to file five patient forms. According to the records, Awerbuch didn’t receive the first warning until the group discovered it was missing more than five dozen forms.
Even after two warning letters and protocol counseling, Awerbuch continued to prescribe TIRF drugs without the proper patient paperwork.
What’s more, the oversight regulators closed Awerbuch’s non-compliance case despite his lacking agreement forms from 53 patients.
Less than a month later, Lopez was dead. The numerous drugs Awerbuch prescribed for her, including Subsys, turned out to be a “lethal cocktail,” according to court records.
“It’s outrageous. It’s very disturbing,” Detroit attorney Brian McKeen said of the lack of action to stop Awerbuch. “These are red flags waving in the wind that any responsible government organization or pharmaceutical company should be heeding.”
McKeen represents Lopez’s estate and her mother in a malpractice lawsuit filed against Awerbuch.
He said Lopez, who long suffered from chronic-pain problems, sought out Awerbuch, who promoted himself as a specialist in chronic pain. He was trained as a neurologist.
Even if Lopez had cancer, she should never have been on Subsys. Warning labels on the box explicitly said the fast-acting fentanyl drug should not be given to patients with respiratory problems because the drug depresses breathing.
With COPD and sleep apnea, Subsys was a ticking bomb for Lopez.
“I don’t think she was aware that this was a drug that was not appropriate for her,” McKeen said. “She trusted her physician to select the appropriate drug. There are too many doctors in this country who are injudiciously prescribing dangerous narcotics . . . resulting in preventable deaths.”
In late 2013 and early 2014, TIRF regulators continued to contact Awerbuch for the same offense: prescribing without the required paperwork.
In May 2014, the regulators became aware that Awerbuch had been arraigned on federal charges of health care fraud and distribution of controlled substances.
Even then, he was not banned from the oversight and safety program.
Two days later, Awerbuch resigned as a TIRF prescriber.
The program’s oversight is run by McKesson and the pharmaceutical companies making the fentanyl drugs. They serve as the primary communicators with the FDA.
They also serve as the enforcement arm, making sure that doctors and pharmacists who prescribed and dispensed TIRF drugs are in compliance with the rules of the safety program.
Today, there are nine drugs in the program, including six brand-name products: Abstral, Actiq, Fentora, Lazanda, Onsolis and Subsys. All are absorbed through saliva.
In 2012, the pharma industry group told the FDA it wanted to stop requiring patient phone numbers on agreement forms.
According to FDA documents, the group claimed that doctors said collecting phone numbers “is affecting their practice of medicine.” McKesson Corp., the large national distributor of drugs, called the phone numbers unnecessary information.
The FDA did not object.
But the group’s main source of communications with the FDA centered on annual assessments of the program, including how many patients and doctors were enrolled and other key metrics.
For years, the FDA raised no major concerns, according to reports.
A letter from one FDA official shows that after five years of reading these assessments, the agency didn’t have a clear picture of how the oversight and safety program was working.
“We conclude it is not possible to determine whether the overarching goal of the REMS - to mitigate the risk of misuse, abuse, addiction, overdose and serious complications due to medication errors – is being met,” wrote Dr. Judith A. Racoosin, deputy director of safety at the FDA’s Center for Drug Evaluation and Research.
Multiple data studies question the ability of TIRF-REMS to prevent patients who don’t qualify for receiving fentanyl prescriptions.
This was highlighted at an August FDA public advisory committee hearing that was called after InvestigateTV’s first story on McKesson’s handling of the TIRF-REMS oversight program. U.S. Sen. Bill Cassidy contacted the FDA after watching the report.
“It is only because of our inquiry that they agreed to hold this public advisory committee hearing and that is a result of your good investigative reporting,” said Cassidy, a Republican from Louisiana.
The FDA and drugmakers require that doctors sign an agreement stating that they understand the TIRF drugs are restricted to opioid-tolerant cancer patients.
But at the FDA hearing, the Centers for Medicare and Medicaid Services testified 72 percent of Medicare patients who were prescribed TIRF fentanyl drugs did not have a cancer diagnosis in the same year. A study by the drugmakers themselves concluded 42 percent of TIRF patients were not opioid tolerant.
“Are doctors lying on the form? Why do we have this disconnect? And if we have this disconnect how can we be concluding that the REMS program is operating and functioning as designed?” asked Steven Meisel, director of patient safety at Fairview Health Services.
The FDA responded that the form asks if the doctor understands that TIRF medicines are for opioid-tolerant cancer patients. “We don’t make certain that the patients are opioid tolerant,” said Doris Auth, FDA associate director of risk management. “There’s also no information about whether the patient has cancer pain or pain related to another source.”
Critics of the program, such as New York lawyer Richard J. Hollawell, compare the agency’s TIRF-REMS oversight and safety program to the fox watching the henhouse.
“The FDA conceded all control to the drug industry and it’s disgusting,” he said.
Hollawell represents parents who lost their 32-year-old daughter to a Subsys overdose and a New Jersey mother who became addicted to the drug. Neither had cancer. Neither was protected by the oversight program.
“The FDA holds itself out that it is the gatekeeper for the protection of the consumer. The FDA is doing the opposite,” Hollawell said. “They are allowing the industry to dictate how these drugs get to consumers, and it’s all in the interest of the drug industry.”
In 2017, the FDA finally flexed its muscle with TIRF drugs.
It instructed the pharma industry group to clearly state that the drugs are intended only for cancer patients and “are not to be used for acute, post-operative, emergency room or dental pain,” FDA records show.
By then, the most popular TIRF drug, Subsys, had left a trail of dead and injured patients and indictments against doctors and company insiders.
At the end of the 8-hour hearing last month, FDA committee members urged more education for prescribers. Currently, doctors must read a nine-page PDF every two years. The FDA has instructed drugmakers to analyze outcomes, such as death of non-opioid tolerant patients taking TIRF drugs.
It all comes too late for those patients who lost their lives.
Within six months of Stephanie Lopez’s death, federal investigators had zeroed in on Awerbuch, her Michigan doctor.
He was arrested in May 2014 on charges of health care fraud and illegally prescribing controlled substances. He eventually pleaded guilty and, in February this year, was sentenced to 32 months in prison.
Though he has sued Awerbuch for Lopez’s death, attorney McKeen said the FDA is not without blame because of its lax oversight.
“It seems like they were acting as Dr. Awerbuch’s enabler,” he said. “It’s very, very concerning.”
On Nov. 10, 2013, Lopez posted on her Facebook page, “simply trusting God ...some days that's all I can manage.”
She laid down for a nap. She never woke up.
“Unfortunately, Dr. Awerbuch did not put their best interests first,” McKeen said. “As a consequence, unfortunately, Stephanie lost her life.”
She was just 30.