Cold Comfort, Chapter 2: “What is Off-label?”

Anyone who has ever picked up a prescription has seen the exhaustive labeling, even on simple, straightforward drugs. Here’s what it is, what it’s for, how often to take it, and, in the fine print, the usual long list of warnings and side effects. The bottom line: drugs are supposed to be prescribed only for what is “on label.” What they were “indicated for,” in pharma-talk. If a certain treatment was approved on the label, the drug was “indicated” for that treatment.

Sometimes, though, a drug can be effective in treating ailments or conditions that it isn’t indicated for. Prescribing drugs for treatments that the FDA has not approved them for is considered “off-label.”

Off-label prescribing by doctors is not illegal, or even unusual, in the history of the pharmaceutical industry and the practice of medicine. Doctors are allowed to prescribe off-label for their patients if they think it might help them.

A drug company sales rep’s job is to promote the company’s drugs and tell doctors who the drugs could help and how—but only within the government-approved guidelines for that drug. The government-approved guidelines for any drug are found printed on the “package insert” for that drug. The PI, as it’s known in the pharmaceutical industry, has all the scientific facts of any drug (pharmacology, pharmacodynamics, controlled studies, dosing, contraindications, and more). It is illegal for drug reps to suggest to doctors that they prescribe any drug off-label for a treatment not approved by the federal Food and Drug Administration from the PI.

The reason for this is simple: the doctor and the drug rep have different jobs. One is to treat the patient and the other is to sell the drug’s benefits from the PI.

We were sales representatives, not gangsters, though. Our role was to do good. We traveled to our assigned sales areas or territories, met with doctors, and told them about the benefits of the various drugs that our company made and sold. We made small talk with the doctors about their families. We asked about their business and talked with them about their patients, what prescriptions they were writing, and what was working and not working.

We asked what sorts of medical problems their patients were struggling with and tried to give doctors information that would provide new strategies for helping those patients. We made suggestions for new or modified treatment and left the doctors with free samples they could pass along to their patients. If a patient tried a new drug from one of our samples and it worked—if it helped—the doctor would prescribe it. The sale would be recorded through the pharmacy that filled the prescription and reported back to the pharmaceutical company.

If a doctor prescribed one of the company’s drugs, the sales rep serving that doctor got credit for the sale and got a commission from the company based on the sales for that month. When the pharmaceutical sales system worked, it worked well, and it helped everybody. Sales reps like me got their commissions, the doctors helped their patients, and—best of all—the patients themselves were healthier. They could lead better, fuller lives and have a higher quality of life. I loved being a pharmaceutical sales rep, and I was pretty good at it.

In the early 2000s, Cephalon began encouraging doctors to prescribe some of our drugs, especially the ones not selling particularly well, for some unintended, untested, unproven treatment. Sometimes the drugs worked for these unintended purposes; sometimes they didn’t. When off-label prescription drugs worked for new and different treatments, doctors looked like geniuses for coming up with this creative new way of using an old drug. The drug company got more sales, and the sales reps got more commissions. On the other hand, sometimes an off-label prescription backfired. It made the patient worse.

Off-label marketing is unethical and illegal and potentially dangerous for patients. My company seemed to be ignoring both the potential dangers to patients and legal issues. This was the second drug company I had worked for as a sales rep and manager, and there had been ethical, potential legal problems at my first employer, too. Those issues drove me away from my first company to take a better job at what I thought was a better company. But here I was, in my second company, facing another ethical dilemma.

The sales reps who worked for me—I had become an area manager—were not simply being asked to sell our drugs off-label. We were being encouraged and trained—and paid very well—to sell our drugs off-label, for medical conditions those drugs had never been expected to treat and were not designed to treat. The threats to our jobs if we didn’t cooperate were becoming less subtle. To work for this company, you needed to show off-label sales results.

I complained, first to my closest coworkers, then to my bosses. I didn’t think selling off-label was right or could ever be justified. It was wrong and not solely because of the federal regulations specifically prohibiting off-label marketing. It was dangerous to unsuspecting patients. I was afraid someone was going to die.

I was starting to be seen as a problem within the company— the one guy who was trying to rain on everybody’s parade, who was trying to squelch all these off-label sales that were helping our reps earn big salaries, often hundreds of thousands of dollars. I complained, but my complaints fell on deaf ears.

Most sales reps didn’t seem to care or shrugged it off. After all, it was the doctors doing the prescribing, not us sales reps. We were just providing information. If something bad happened, it wasn’t our fault. And, hey, did you see the sales numbers for last month? We were getting rich from selling drugs off-label, whether they worked or not. It didn’t take long for the hypocrisy to get to me. My career suffered. My sales suffered. In turn, my relationships suffered, not just at work. I took my unhappiness home with me and paid the price for it eventually.

When I stumbled into whistleblowing, it was more by accident than on purpose. I didn’t go looking for the authorities. Someone else saw what was happening and confronted me and challenged me to step up. I had no idea what it would cost me. If I had known then what I know now, things might have been different. If I had known what my life would be like as a whistleblower—the rest of my life, actually—I might have thought more carefully about that first meeting with two federal agents in a nondescript franchise hotel lobby.

Greg wasn’t an FBI agent, but he was with a comparable, parallel investigative arm within the federal Food and Drug Administration, the FDA’s Office of Criminal Investigations. The role of his agency was to investigative wrongdoing within the pharmaceutical industry. Sometimes the drug companies paid fines—often very large fines, in the tens or hundreds of millions of dollars. In especially egregious cases, the investigations led the Department of Justice to seek prison time for the people involved; they could be management and all the way up to the CEO.

In 2019, the opioid maker Insys was fined $225 million for off-label marketing of its sublingual fentanyl spray, SUBSYS, a powerful but highly addictive opioid painkiller. In this case, reps, managers, and executives were arrested for racketeering.

Nearly 20 years earlier, Cephalon’s drug Actiq, a potent opioid, a hundred times stronger than morphine and administered by a lollipop, was one of the handfuls of drugs that the company was peddling in off-label promotion that year.

“Bruce,” asked the agent, “will you wear a wire?”