Is Genetic Testing for Addiction Real or Just a Scam? There’s Still a Lot to Proove
“Any expert in the field would tell you that genetic vulnerability to addiction would involve dozens of SNPs [single nucleotide polymorphisms]. The idea that anyone would say they are currently able to definitively evaluate an individual’s genetic vulnerability to addiction testing by 1,2 or 20 variants is quite frankly absurd.”
–Dr. Mary Jane Kreek, Addiction Genetics Researcher, Rockefeller University
“We are nowhere near having any diagnostic test for a disease as complex as a psychiatric disorder. We don’t have a single group of genes to say this is the culprit, that this is what’s causing addiction.”
– Dr. Zena Samaan, Genetics Researcher, McMaster University
The above quotes are from addiction genetics researchers on the current state of our ability to use genetic testing to determine if an individual is susceptible to addiction. These quotes seem clear enough that currently we can’t test for addiction risk genetically and it will probably be a complex task, if it can ever be done. Then why are companies claiming they can provide such testing and charging thousands of dollars to do so?
There were two major companies marketing genetic testing for addiction susceptibility: Proove Biosciences and Canterbury Healthcare’s Innovative Medical Testing. In a highly unregulated market of genetic predictive testing for addiction with a host of dubious and exaggerated claims, how do you know if the test you’re taking can reliably provide the information you are seeking or is just an expensive fraud?
The federal government is beginning to share these concerns with an anxious public, if a raid on Proove Biosciences offices in August 2017 is any indication. While testing to determine if you could end up addicted to drugs or alcohol sounds helpful on the face of it, unreliable or even worthless results could actually do more harm than good. If many genetic researchers and experts are saying the science isn’t there yet to make such testing reliable, what are these companies selling and for what purposes?
In 2015 alone, 318 physicians ordered 197,000 reports from Proove, including the Proove Pain Perception Test, Proove Opioid Response, Proove Opioid Risk Profile, Proove Drug Metabolism Test, and others. When the out-of-network cost for a Proove test is $1000 and in-network of $100, without including co-pays or deductibles, it’s easy to see how Proove took in $28 million dollars in revenue last year. The questions remain: are these testing results valid and reliable and if so, what can the information tell us about the prediction of addiction risk for any individual?
Federal Raid on Proove Biosciences Forces Company into Receivership
Proove Biosciences shut down at the end of August 2017 and was placed into court-ordered receivership for restructuring and asset sale. This move comes after a raid in June by FBI and Department of Health and Human Services agents on Proove’s corporate offices in Irvine, California where truckloads of documents were seized in pursuit of a criminal investigation. Proove’s founder and CEO, Brian Meshkin, was removed and GlassRatner Advisory & Capital Group’s Michael Thatcher was appointed by the court as receiver. Meshkin started Proove in 2009 with his own funds but reached out to Leavitt Equity Partners in 2015 for an initial infusion of $3.5 million dollars of funding to expand its market reach.
Michael Leavitt, former Utah governor and former head of the U.S. Department of Health and Human Services, heads Leavitt Equity Partners. Leavitt also had a seat on Proove’s board of directors after the group’s investment. Leavitt requested the receivership after reports came to light of the company’s exaggerated scientific claims regarding its genetic testing for addiction, unethical and possibly illegal business practices to promote unnecessary testing, and kickback schemes in the form of “research fees” for participating physicians.
Was Proove Really Testing for Addiction?
It’s a fairly safe bet that the federal government will be pursuing charges against Proove regarding their business practices and validity of their testing products. Proove was providing, among other genetic prediction tests, the Proove Opioid Risk Profile, determined by a cheek swab for DNA paired with a 6-question patient survey of psychosocial factors on an individual’s past history of depression and substance abuse.
The questionnaire is drawn from the Opioid Risk Tool (ORT), a widely used addiction screen, developed by Dr. Lynn Webster, a board member of Proove. While the ORT is widely used, it is a self-administered survey instrument that has the limitations of any self-survey compounded by the human predilection to underestimate or hide behavior that is negative, shameful, or displeasing to others, a behavior that can skew results. Meshkin, former CEO and founder of Proove contended the combination of the objective genetic test results would balance the subjective ORT results and produce a more reliable predictive instrument.
The DNA from the cheek swab is tested for 12 gene variants, also known as SNPs (single nucleotide polymorphisms), that may influence the brain’s reward pathway, a system thought to have some effect on an individual’s susceptibility to addiction. The test results are run through an algorithm process developed by Proove to combine the ORT data with the DNA testing results to place patients in low, moderate, or high risk category for addiction.
As Dr. Eduardo Butelman, an addiction researcher at Rockefeller University, stated,
“There are no data on how you can build a risk score by combining all of those [SNPs] together and no one has shown mathematically how you can combine that genetic information with environmental information.”
Current genetic science doesn’t establish reliably and replicably what data should be tested for and how the data should be combined to produce a predictive result of addiction susceptibility, assuming, of course, that genetic testing can test for addiction risk. The science of genetic testing for multivariate issues, like addiction, hasn’t been established when we don’t even know what we’re looking for or if it can be tested genetically at all.
Did Your Doctor Sell You Out to Proove?
Despite this lack of data, Proove testing has been in use at National Spine and Pain Centers, University of Southern California Pain Center Keck School of Medicine Pain Management Center, and Hoag Orthopedic Institute, as well as many private clinics and physicians offices nationwide. Proove has claimed a 93-96% accuracy for their predictive testing for addiction risk without producing a database of referential information to back up these claims. Supporting data cited by Meshkin for the validity of its testing process has been called into question. The data to support Proove’s research and testing was disavowed by both Dr. Eric Fung, the former chief scientific officer of Proove, and Dr. Daniel Schwartz, Proove’s former research and development director of Proove.
Former Proove employees have claimed Proove representatives in clinics and doctors’ offices were encouraged to push for unnecessary testing to increase company revenue, and that these test results were often contradictory and/or falsified. Rhonda Frantz-Smith, former senior manager at Proove, has stated Meshkin wanted all patients tested for addiction susceptibility in clinics and doctors’ offices that worked with Proove, whether they needed it or not.
Canterbury Keeping Mum on How and What They Test for Addiction
In case you’re thinking about heading to Canterbury for your genetic addiction testing, you might want to consider that Canterbury declines to disclose any of their testing process at all. Canterbury has focused their marketing on helping employers reduce the risk and cost of workmen’s compensation. Their selling point is to attempt to predict addiction risk and thus avoid prescribing narcotics to employees with a high risk for developing addiction.
The company provides no information on the gene variants it screens for nor whether it takes into account the many psychosocial and environmental factors that scientists believe contribute 40-60% of addiction risk, if it even can be predicted. Most addiction and genetic authorities agree that prediction of addiction risk is multifactoral in nature and we can’t reliably assess that risk through genetic testing now. With the complexity of factors involved, it may not ever be possible to test genetically for such risk.
LDTs: Growing Without Any Regulation- A Modern Medicine Show?
Many genetic tests, including addiction risk assessments, falls under the FDA category of laboratory-derived tests (LDT). LDTs are largely unregulated and there may be as many as 60,000 or more of these tests available commercially. The LDT category was developed in 1976 as somewhat of a catchall and long before genetic testing was viable at all.
The FDA has no real structure to follow or ability to regulate the LDT category. Historically, tests in LDT category have fallen into a hands-off observer mode. The FDA had promised that it would develop a regulatory pathway for this exploding field for 2010, but it has yet to do so. Currently, the FDA specifically regulates testing for disorders with a defined inheritance pattern and diagnostic tests to help predict patient response to drugs in terms of sensitivities and effectiveness. These tests have followed a standard device approval pathway and, since the testing issues for these tests are relatively uncomplicated, this is appropriate.
Genetics Experts Say Don’t Fall for Addiction Testing
Multifactorial testing for issues like addiction potentially could include several variants that may correlate with addiction risk, probable unknown variants, and the interpretation and integration of psychosocial factors into the test results to even approximate a valid outcome. At present, several factors complicate the validity and reliability of such testing, including a lack of data on such testing’s ability to accurately predict addiction risk and a lack of replicable results for this type of testing.
Another concern with genetic testing for addiction susceptibility involves how the information is interpreted and used by the doctor and patient, especially as the testing at present has limited reliability and may not even be accurate. Jehannine Austin, past president of the National Society of Genetic Counselors and associate professor of psychiatry and medical genetics at the University of British Columbia, has stated concerns with using genetic testing currently to predict opioid addiction:
“Opioid addiction, like most behavioral traits, is a very complex issue that is hugely unlikely to be comprehensively explained by a small set of genetic variations. Most human behaviors and common conditions like addictions seem to result from the combine effects of genes and experiences working together…I worry that this is too simple of a strategy to address the real issue.”
In addition, Dr. Austin expressed concerns that people would misinterpret the genetic role in addictions, if it exists, and that receiving any result, whether false negative or false positive, might overly influence their life decision making,
“There is a danger associated with people assuming that any problems that they have with addictions are entirely genetically determined. It can lead to fatalism or overestimation of risk for children experiencing similar problems.”
The American Association for the Advancement of Science (AAAS) put out a press release in May of 2014 touting research on a new test to predict an individual’s risk for alcoholism. It was composed of testing 11 genes reportedly linked to individuals who were having problems with alcohol use.
Cecile Janssens, a leading expert on risk prediction with DNA testing and researcher in translational epidemiology at Emory University, exposed the press release for inflating the value of the test. The actual predictive value of the test was the equivalent accuracy of a coin toss for predicting alcoholism as the difference between the alcoholic and control groups were so slight. The researchers were clear on this point in their article but the press release heralded a test that “may be possible someday for young people to take a blood test and learn if they’re susceptible to alcoholism.”
In fact, the collection of 11 genes does not predict alcoholism for groups or individuals. The test was an attempt to gather testing for genetic variations that were thought to occur in correlation with alcohol abuse. When the testing was analyzed, the differences between the control group with no alcohol issues and individuals with reported alcohol use problems were insignificant. The predictive ability of the test was negligible but the correct interpretation just wasn’t exciting enough to override the desire for a quick, simple test to predict addiction risk. The press release shamelessly promoted an inflated outcome and it was, of course, picked up by media as a step closer to addiction testing. When we prefer to print our desires rather than the science, as Dr. Janssens concludes, “that is pretty bad news”.
Diagnostic Accuracy and Innovation Act- Help Is Still in the Distant Future, If at All
In effort to rein in this unregulated field of LDTs, including genetic testing for addiction susceptibility, Representatives Diana DeGette of Colorado and Larry Bucshon, MD, of Indiana proposed the 215-page draft of the Diagnostic Accuracy and Innovation Act (DAIA) on March 21, 2017. Both representatives serve on the House Committee on Energy and Commerce and are co-sponsoring the bill.
The bill would serve to create a new category of In Vitro Clinical Tests (IVCTs) as well as a new center for their regulation under the FDA. The bill’s potential is far reaching and could have a dramatic effect on many industries so it is moving with slow deliberation and extensive public comment. The fact that real regulation is being contemplated for this area for the first time since 1976 is, in itself, a move in the right direction.
The current bill excludes testing related to forensic, genealogical, and drugs of abuse (DOA) results and formulates a new structure where LDTs would be classified as high, moderate, and low risk testing. Some have expressed concerns that requiring significant oversight could slow down innovations and price small labs without substantial capital out of the LDT market in providing novel and unique testing.
Considering that available testing is being promoted as having validity and reliability with little or no data to substantiate these claims and is being used for significant medical treatment and lifestyle decision making, the free for all atmosphere of LDTs simply can’t continue.
Genetic Testing Today—We’re Preparing to Take Baby Steps
Genetic testing is a valuable tool and will likely grow in its reliability to predict and diagnose diseases, illnesses, and conditions of all sorts. Despite our advances, we are still working mainly in the dark. The genetic difference between any two random people is 99.9% the same. That 0.1% difference involves 3 million possible differences between each individual’s 3 billion base pairs of the DNA sequence. Currently, genetic researchers have only determined 5% of the variances that may prove to have an influence on addiction risk. Or, put another way, “more than 95 percent of the genetic variance remains unaccounted for, indicating that most of the genetic risk factors for addiction have not been discovered yet.”
We know that DNA encodes many physical traits, illnesses, and diseases. We also surmise that certain conditions and diseases may have a susceptibility or trigger built into our genetic code. What those conditions and diseases are that have genetic influences and what constitutes the environmental and psychosocial triggers that may influence whether a condition or disease presents itself is largely speculative at the present.
When we consider that genetic testing beyond the relatively easy diagnostics for specific known mutations that lead to specific known outcomes is largely unknown, we realize we are in the prenatal stage of our genetic understanding. We are very unlikely to find ‘the’ addiction gene. If addiction can be predicted genetically, it will more likely be a mix of SNPs that may form very individual profiles along with the influence of personal and environmental factors.
At best, genetic researchers today feel genetic coding may have some influence on whether an individual experiences addiction in their life. The far greater influence-likely 40-60% of the influence- as to whether a person experiences alcohol or drug addiction remains environmental and psychosocial factors, including the influence of personal and cultural belief systems.
Would Knowing You Had the Addiction Gene Help? Study Shows Probably Not
If there were a test that could reliably tell you if you had a genetic predisposition to addiction, would you take it? Would knowing the results of addiction testing help you to control your behavior and avoid addiction entirely? Or would knowing the results make you feel doomed to a life of addiction and even disable any preventative behaviors and beliefs you held that protected you? Would you use the information to make life decisions that steered you away from addiction or plunge headlong into addiction with fatalistic abandon?
Having the knowledge of addiction through genetic testing may not even be useful to patients. A study at the University of Sydney found that telling people they possessed a gene for alcoholism resulted in an increase in their negative emotional feelings as well as feeling less in control of their drinking behavior (Dar-Nimrod, Zuckerman, and Doberstein, 2012). Prevention may actually be circumvented by genetic testing results if the individual forms or believes in a fatalistic view of genetic information over their own self regulation of behavior. These predictive test results shared with patients could actually disrupt their natural protection against addiction and their control of self-destructive behaviors.
At the present time, genetic testing to predict addiction risk is, at best, unreliable. There is evidence that knowledge of such risk could be damaging to some individuals if they have a fatalistic view of their ability to control their behavior and overly subscribe to the influence of genetics on complex life experiences like addiction. Rather than thinking of addiction as a binary choice of yes or no, our current knowledge of addiction shows we are heavily influenced by our environment and psychosocial factors. What we know and believe of substances and addiction, both personally and culturally, has far more influence on our relationship with substance use than genetics alone.
As humans, it is an almost universal wish to find simple, quick solutions to complex issues. Taking a blood test or a cheek swab and getting a quick result of how addiction may present in our lives sounds desirable at first. In reality, such information would paint a poor portrait. Our ability to assimilate accurate information on substances, cast aside addiction mythology, and ultimately utilize our self-awareness, behavioral control, and personal accountability will always trump any genetic variations that are merely a potential starting point in a chain of complex decisions and desires that form the heart of addiction behavior. Addiction is simply too complex a set of behaviors to be governed completely by genetics alone, if it is governed at all.