The Food and Drug Administration, drug companies and doctors mishandled distribution of a powerful fentanyl painkiller, allowing widespread prescribing to ineligible patients despite special measures designed to safeguard its use, according to a report released Tuesday.
The unusual paper in the medical journal JAMA relies on nearly 5,000 pages of documents that researchers obtained from the government via the Freedom of Information Act, rather than a more typical controlled scientific study.
After reviewing the data, the researchers concluded that prescribers, pharmacists, drug companies and the FDA — all of whom had agreed to special rules and monitoring for use of the powerful opioid — had allowed it to fall into the hands of thousands of inappropriate patients. Over time, the FDA and drug companies became aware this was happening but took no action, the researchers found.
Using five years of insurance claims data, the researchers found that between 34.6 percent and 55.4 percent of patients shouldn’t have received the drugs.
“The whole purpose of this distribution system was to prevent exactly what we found,” said Caleb Alexander, co-director of the Center for Drug Safety and Effectiveness at the Johns Hopkins University Bloomberg School of Public Health, and one of the leaders of the study. “It should never happen. It’s a never event. And yet we found it was happening in 50 percent” of the cases.
The researchers looked at the distribution of pharmaceutical fentanyl for cancer patients experiencing “breakthrough pain” despite receiving opioids round the clock. The fentanyl, administered via lollipops, lozenges or nasal spray, marketed under several names by different companies, is about 100 times as powerful as morphine. According to the FDA, about 5,000 people in the United States receive such prescriptions at any one time.
In a statement, a spokesperson for the FDA said the agency “shares the concerns” about how the drug is being prescribed and whether its safeguards are working.
“These products are medically important for a small group of patients who are opioid-tolerant but also pose serious risks. That’s why the agency has sought to ensure that the. . . program is achieving its public health goal of assuring safe use and mitigating the risks of misuse, abuse, addiction, overdose and complications due to medication errors.”
The JAMA paper comes during the trial in Boston of Insys Therapeutics founder John Kapoor, who is accused of racketeering. Prosecutors say that the company paid doctors kickbacks to increase the use of its product Subsys, a form of fentanyl that is sprayed under the tongue for pain relief, and encouraged them to offer higher doses.
The strength of pharmaceutical fentanyl products and their quick absorption through the mucosal linings of the mouth and nose pose a serious risk of overdose, abuse and addiction for anyone who hasn’t already built up a tolerance to opioids. To guard against prescribing to such patients, the FDA created a “risk evaluation and mitigation strategy” for the products.
Under the plan, drug companies, doctors, pharmacists and patients themselves received special instruction on the use of the drugs and signed up to be part of the small, closed group allowed to prescribe, dispense and take them. Drug companies and the FDA monitored prescribing.
But the report contends that those safeguards didn’t work. In an assessment of claims data after four years, the drug industry told the FDA that 12,916 of 25,322 patients who took the drugs, or about 51 percent, had not built up tolerance to opioids, according to FDA standards.
A report after 60 months determined that 34.6 percent to 55.4 percent of patients were ineligible, depending on the product, the Hopkins researchers reported. The FDA concluded that its primary goal of keeping the drug out of the hands of ineligible patients was not being met.
The FDA responded to a few complaints that the rules tied the hands of clinical decision-makers by making the definition of opioid tolerance more specific, the report shows. Doctors have authority to prescribe medications “off-label” — for problems other than those spelled out on the drug packaging. But in this case, the drugs were specifically prohibited for patients who weren’t already tolerant of other opioids.
Drug companies were supposed to boot doctors and others who wrongly prescribed the drugs. But after two years, and in subsequent analyses, the researchers found “no reports” of the medications “being prescribed to an opioid non-tolerant individual.” No prescriber was cut from the program despite the results available in the claims data, they said.
“Manufacturers agreed to a sort of comprehensive prescriber monitoring, and clearly that broke down,” Alexander said in an interview. “If that were working, prescribers would have ben rapidly disenrolled who were prescribing inappropriately.”