Drugs Used Off-Label Need More Research
Newswise — Many prescription drugs are valuable in treating diseases for which they were not approved, but doctors, insurers and drug-makers have little to guide them in how to evaluate the safety, efficacy and cost-effectiveness of these drugs in their "off-label" uses.
A new study by the Chicago-area Developing Evidence to Inform Decisions about Effectiveness (DEcIDE) Center at the University of Illinois at Chicago provides a way of identifying which drugs are most in need of study for their off-label use -- and offers a top-priority list of 14 candidates.
Once a prescription drug receives approval from the U.S. Food and Drug Administration, physicians may prescribe the medication for conditions other than those for which it was approved. Off-label use is widespread even though it is unlawful for drug companies to promote such use.
The new study, led by Surrey Walton, UIC associate professor of pharmacy administration, provides a prioritized list of drugs being used off-label and most in need of targeted research into the effectiveness and safety of those off-label uses.
Walton led a nine-member panel of university researchers, representatives from the FDA and the health insurance and pharmaceutical industries in developing a "weighted model" of which off-label drugs should get priority for further study.
The model weighs three factors -- the amount of a drug's off-label use; concern about the drug's safety; and a combination of cost, length on the market and past advertising.
"Our findings identified a high volume of off-label prescribing -- in the absence of good evidence -- for a substantial number of drugs, particularly antidepressants, antipsychotics and anxiolytics/sedatives," Walton said.
Thirty months of prescribing patterns were analyzed in the study. The model excluded pediatric off-label use, vaccines, non-drug products and over-the-counter medications. Also excluded were cancer-related drugs, which have received more attention regarding their off-label use, Walton said.
Among the drugs found most in need of further study were six antidepressants, including two serotonin reuptake inhibitors (escitalopram and sertraline), two serotonin- and norepinephrine-reuptake inhibitors (venlafaxine and duloxetine), and two of another class (bupropion and trazodone).
Three antipsychotics (quetiapine, risperidone and olanzapine) were also among the high-priority drugs, Walton said.
"The most common conditions prompting their use were bipolar disorder, depression and dementia," he said. "This may result from the lack of entirely acceptable and effective treatments, as well as overlapping clinical characteristics."
The remaining drugs on the list were the anticoagulant warfarin; montelukast, used for the treatment of asthma; celecoxib, for arthritis; lisinopril, an ACE inhibitor; and epoetin alfa, to treat anemia.
Walton said the study was not intended to determine whether the use of prescription drugs off-label was good or bad, as some drugs have been used effectively this way. Others have not worked as well.
"Physicians may have a clinical insight into the drugs they are recommending to patients that are not indicated for their condition, and they may think that it will be helpful. This can lead to learning, or it may be risky," he said. "The most important finding from our study is that more research would be valuable before using these drugs off-label."
Prior studies of off-label prescribing have focused on children and on psychiatric disorders, bacterial infections and "orphan" clinical conditions. Those studies demonstrated that off-label use is frequent, even with varying evidence supporting such uses, Walton said. The studies also identified disease- and patient-specific situations where off-label use may be beneficial.
The new study, published in the December issue of the journal Pharmacotherapy, was funded by the U.S. Agency for Healthcare Research and Quality. Co-authors include Dr. Randall Stafford of Stanford University, Drs. G. Caleb Alexander and David Meltzer of the University of Chicago, Ky-Van Lee, formerly of Stanford and currently at Gilead Sciences, Inc., and Glen Schumock, director of UIC's Center for Pharmacoeconomic Research.
For more information about UIC, visit http://www.uic.edu.
