Proove claims its test can predict, with 93 percent accuracy, which patients will become addicted to or misuse prescribed opioid pain pills.
That’s been an irresistible sales pitch for many physicians, who struggle to treat pain patients compassionately but fear adding to the national epidemic of opioid addiction.
The Irvine, Calif., company has recruited 400 doctors, who have used the test to guide their treatment of more than 100,000 patients in the last five years.
Genetics and addiction experts — including one of Proove’s medical advisers — said genetic testing isn’t able to predict addiction, and questioned the evidence used to back up the company’s accuracy claim.
Erroneous results could misinform doctors and lead them to unnecessarily refuse opioids to patients suffering severe pain, the experts warned.
Tests represented as authoritative and scientific without convincing evidence smack of “opportunism” and exploit understandable alarm about opioid addiction, said Leigh Turner, a bioethicist at the University of Minnesota. “If the company says ‘trust us,’ and provides no peer-reviewed data, it’s important to be wary.”
Rockefeller University’s Dr. Mary Jeanne Kreek, a leading researcher on genetic links to addiction, said Proove’s test — which combines a standard patient questionnaire with genetic data — was “hogwash.”
How refreshing to hear a knowledgeable person give an informed opinion in such pain language.
That hasn’t kept Proove, which is paid an average of $300 for each test, from taking in an estimated $28 million in revenue this year for that genetic test and others, most of them related to pain drugs or pain perception. It has been ranked among the nation’s fastest growing firms by Deloitte Consulting and Inc. magazine.
Proove is one of an expanding number of players in the multibillion-dollar genetic testing market that promote tests unsupported by hard data to doctors and consumers — and because of a regulatory loophole, it’s all legal.
These tests have proliferated with the emergence of personalized medicine and its promise to tailor treatments to patients, and the rapid drop in the price of sequencing genes.
Beyond the immediate impact on patient care, unreliable predictions based on inherited addictive traits, once entered in a patient’s electronic medical record, might cause future problems, said Wayne Hall, an addiction ethics expert at Queensland University in Australia.
“If patients are hospitalized with severe pain after something like a [heart attack], and are being treated for post-operative pain, physicians might be reluctant to prescribe opioids that they really need,” said Hall. “If a family member was diagnosed by this test as being at a high risk of opioid dependence, then physicians may well be reluctant to prescribe to other family members, to children.”
After an attempt to strike it rich with web marketing during the dot-com boom, then a stint in pharmaceutical marketing, in 2007 Meshkin started Salugen, a “nutrigenomics” company. It sold “GenoTrim” — a genetic test to customize weight-loss supplements — through Las Vegas spas and directly to consumers.
In 2008, California health authorities sent Salugen and other direct-to-consumer genomics firms a cease-and-desist letter for improper marketing. Salugen shifted to working with doctors who ordered tests for patients, and the company was later sold.
Meshkin started Proove in 2009 based on the Haveos concept: Given the hazards of a pill-popping era, he thought personalized pain care could be the next big market.
Rust, who operated one of the study sites, said Proove had requested only insured patients adding, “They signed me up to do a study, when really what they were wanting was to get more business. … I saw it as more of a marketing effort.” Rust said Proove dropped him from the study for unstated reasons after it became clear that not all of his patients were insured.
Hall, the medical ethicist, questioned the adequacy of Proove’s informed consent form signed by trial volunteers, because it fails to mention the risks of being judged genetically susceptible to opioid dependence.
Veneer of science
Proove’s opioid risk test incorporates a questionnaire similar to one widely used by clinicians who rely on patient histories and symptoms to guide their prescribing practices for pain patients. That widely used tool, developed by Dr. Lynn Webster, a member of Proove’s medical advisory board and a past president of the American Academy of Pain Medicine, uses questions about a patient’s personal and family history with drugs and mental health to help doctors identify patients at risk of possible misuse of drugs or addiction
Meshkin discounted the value of such questionnaires by themselves, however, because drug-seekers often lie about their history, and patient reports about how opioids affect them can be hard to interpret.
Proove sales materials describe clinical judgments as “no better than flipping a coin.”
Webster strongly disagreed. “[M]ost physicians know, if a patient has a history of opioid abuse, they are at a much greater risk of abusing opioids when prescribed for pain,” he said. “Their personal history, their family history of substance abuse, mental health disorders … all increase the risk. It is not a coin flip.”
Leading researchers said the science of predicting behavior involving opioids and other addictive substances is still in its infancy.
“It’s not time yet. We don’t have enough information” to make accurate predictions about genetic causes for addiction, Rockefeller’s Kreek told STAT.
“We have identified 110 gene variants that are highly significantly associated with severe opiate addiction,” but even if a patient had all 110 — instead of just the 12 that Proove checks — it would not necessarily predict behavior, she said.
“Genetic testing is informative. It can help. But we’re not at a point where we can use genetic testing to predict addiction.”
Author: Dr. Lynn Webster, Proove medical adviser