Researchers develop data-driven methods for analyzing off-label drug use

February 20, 2014 by Molly Sharlach, Stanford University Medical Center

(Medical Xpress)—Physicians often prescribe drugs for unapproved indications, but current methods of tracking these off-label uses are limited in scope.

Now, a study by researchers at the Stanford University School of Medicine describes a way to extract and sort valuable information about off-label uses from . The study's authors hope their findings will help to jump-start research into off-label uses that are promising, low-risk and low-cost, as well as flag potentially risky uses for further review.

Drugs prescribed for unapproved conditions, dosages or age groups account for 21 percent of all U.S. , according to a 2006 investigation published in the Archives of Internal Medicine. But only 27 percent of such uses are supported by robust science.

These statistics are not as alarming as they seem at first glance. The lengthy, costly drug-approval process makes a certain amount of off-label drug use inevitable. Off-label prescriptions are legal in most cases and can be an important source of innovation to accelerate new uses for drugs.

Nigam Shah, MBBS, PhD, assistant professor of medicine and senior author of the new study, believes better tracking and investigation of off-label use can help patients, physicians and regulators, but should also appeal to drug companies, who will benefit from new approved uses for their products. "Just as detection of abnormal spending is now a routine feature of credit card services, someday off-label use detection could be a routine part of health-care systems," Shah said.

The National Disease and Therapeutic Index relies on physician surveys to monitor off-label prescriptions, but the index is far from comprehensive. "We wanted to describe the whole universe of off-label use," said Kenneth Jung, a graduate student in biomedical informatics and the lead author of the study, published Feb. 19 in PLOS ONE.

For an extensive view of off-label drug use, Jung, Shah and their colleagues turned to STRIDE, the Stanford Translational Research Integrated Data Environment, which hosts a comprehensive warehouse of de-identified clinical notes, diagnoses and prescriptions for nearly 2 million patients treated since 1994 at Stanford Hospital & Clinics and Lucile Packard Children's Hospital Stanford.

The researchers built a program to run 9.5 million clinical notes from the STRIDE warehouse through the National Center for Biomedical Ontology Annotator, a tool funded by the NIH and designed to pick out names of drugs, diseases and from any text. After filtering their results and checking them for scientific support in the medical literature, they generated a final list of 403 off-label drug uses.

To prioritize these uses for further study, the researchers took into account the cost of each drug and its risk of causing adverse reactions. They used these two parameters to rank each drug use. "Then we placed them into good and bad buckets," Shah said. The "bad bucket" of high-cost, high-risk uses should raise red flags that prompt re-evaluation by physicians and regulators.

For indications in the "good bucket," Shah hopes to expedite tests in cell lines and mouse models. Positive results from these experiments may ultimately lead to clinical trials and new approvals. "The combination of and molecular evidence can make a stronger argument for agencies to fund clinical trials," said Shah, who is also a member of the Stanford Center for Biomedical Informatics Research.

Among the highest-risk drugs were immunosuppressants and anti-tumor agents. One of these was rituximab, an antibody that destroys the B cells of the immune system. It's approved for leukemia and lymphoma, but records show it's also used to treat purpura, a bleeding disorder that causes red or purple patches to appear on the skin. The study suggests that the high cost and considerable risk of severe reactions warrant further study before pursuing this use of the drug.

On the other hand, folic acid appeared to be a low-risk, low-cost treatment for a range of conditions, including mental depression, diarrhea and high cholesterol. Also known as vitamin B9, folic acid is found in some fruits, vegetables and whole grains, but patients often need a supplement to get enough to treat their condition. Also in the "good bucket" was the use of megestrol for patients with non-small cell lung carcinomas; the drug has traditionally been used to relieve symptoms in breast and endometrial cancer patients.

Jung was surprised by how many of the novel uses were predictable based on prior knowledge. "A lot of it actually made sense," he said. "We should have known about some of these uses already. This gives us confidence that the method we developed works."

However, this method cannot yet detect unapproved drug uses by age, sex, dosage or other contraindications. The researchers caution that some adverse reactions to drugs and co-morbidities—patient conditions unrelated to the prescribed drug—could have muddled their results. The team members said they will gain more confidence if they see similar outcomes when they apply the same methods to analyze electronic medical records from other hospitals.

Explore further: Novel chemotherapies more often used on- than off-label

Related Stories

Novel chemotherapies more often used on- than off-label

February 26, 2013
(HealthDay)—In contemporary practice, medical oncologists use novel anticancer agents on-label more often than off-label, according to a study published online Feb. 19 in the Journal of Clinical Oncology.

Off-label drug use common, but patients may not know they're taking them, study finds

August 6, 2012
Many people have probably heard of off-label drug use, but they may not know when that applies to prescriptions they are taking, a Mayo Clinic analysis found. Off-label drug use occurs when a physician prescribes medication ...

Research suggests off-label prescribing of medications is common

April 16, 2012
A study evaluating off-label prescribing of medications in a primary care network in Canada suggests the practice is common, although it varies by medication, patient and physician characteristics, according to a report published ...

Problems continue with inappropriate prescription of antipsychotic drugs

November 7, 2013
Low-dose, antipsychotic medications are continuing to be widely prescribed, a new analysis suggests, even though it's likely many of the prescriptions are for conditions where there's weak evidence of their effectiveness ...

Mining information contained in clinical notes could yield early signs of harmful drug reactions

April 10, 2013
Mining the records of routine interactions between patients and their care providers can detect drug side effects a couple of years before an official alert from the U.S. Food and Drug Administration, a Stanford University ...

Recommended for you

In most surgery patients, length of opioid prescription, number of refills spell highest risk for misuse

January 17, 2018
The possible link between physicians' opioid prescription patterns and subsequent abuse has occupied the attention of a nation in the throes of an opioid crisis looking for ways to stem what experts have dubbed an epidemic. ...

Patients receive most opioids at the doctor's office, not the ER

January 16, 2018
Around the country, state legislatures and hospitals have tightened emergency room prescribing guidelines for opioids to curb the addiction epidemic, but a new USC study shows that approach diverts attention from the main ...

FDA bans use of opioid-containing cough meds by kids

January 12, 2018
(HealthDay)—Trying to put a dent in the ongoing opioid addiction crisis, the U.S. Food and Drug Administration on Thursday slapped strict new restrictions on the use of opioid-containing cold and cough products by kids.

Taking ibuprofen for long periods found to alter human testicular physiology

January 9, 2018
A team of researchers from Denmark and France has found that taking regular doses of the pain reliever ibuprofen over a long period of time can lead to a disorder in men called compensated hypogonadism. In their paper published ...

Nearly one-third of Canadians have used opioids: study

January 9, 2018
Nearly one in three Canadians (29 percent) have used "some form of opioids" in the past five years, according to data released Tuesday as widespread fentanyl overdoses continue to kill.

Growing opioid epidemic forcing more children into foster care

January 8, 2018
The opioid epidemic has become so severe it's considered a national public health emergency. Addiction to prescription painkillers, such as oxycodone and morphine, has contributed to a dramatic rise in overdose deaths and ...


Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.