“That everyone shall exert himself in that state of life in which he is placed, to practice true humanity towards his fellow men, on that depends the future of mankind.” – Albert Schweitzer 

“By and by never comes” –St Augustine

“A day’s impact is better than a month of dead pull”-Justice Oliver Wendell Holmes, Jr.

---

 I am looking for a few honest and credible statisticians, biostatisticians or epidemiologists who want to make a difference in the spirit  of service and helping others.  I can’t pay you but you would be combating injustice, corruption and dishonesty.   You would be doing your part in helping the Medical Profession, honest and decent doctors, our country and  perhaps our future.  

It is only a few public policy steps and minor changes in state regulatory statutes before what is described in the ASAM White Paper on Drug Testing comes to fruition.  Before we know it the Drug and Alcohol Testing Industries “New Paradigm” as described here by Robert Dupont will be ushered in as it did with doctors; not with a bang but a whimper.  From the ASAM white Paper:

“THIS WHITE PAPER ENCOURAGES WIDER AND “SMARTER” USE OF DRUG TESTING WITHIN THE PRACTICE OF MEDICINE AND, BEYOND THAT,BROADLY WITHIN AMERICAN SOCIETY. SMARTER DRUG TESTING MEANS INCREASED USE OF RANDOM TESTING* RATHER THAN THE MORE COMMON SCHEDULED TESTING,* AND IT MEANS TESTING NOT ONLY URINE BUT ALSO OTHER MATRICES SUCH AS BLOOD, ORAL FLUID (SALIVA), HAIR, NAILS, SWEAT AND BREATH WHEN THOSE MATRICES MATCH THE INTENDED ASSESSMENT PROCESS. IN ADDITION, SMARTER TESTING MEANS TESTING BASED UPON CLINICAL INDICATION FOR A BROAD AND ROTATING PANEL OF DRUGS RATHER THAN ONLY TESTING FOR THE TRADITIONAL FIVE-DRUG PANEL.”

To prevent this future drug testing dystopia, that includes testing schoolchildren, we need to take a step back and analyze the reliability and credibility of the “evidence-base” behind these multiple non-FDA approved forensic drug and alcohol tests and testing devices the ASAM proposes be used on the population at large utilizing the Medical Profession as a urine collection agency and bypassing forensic drug testing protocol by calling this “evaluation” and treatment rather than “monitoring” and punishment. New definitions, loopholes, secrecy and subterfuge are the bread and butter of these prohibitionist profiteers.

Amazingly, there has been no Academic review of these tests, let alone a Cochrane type critical analysis.  It is essentially untapped territory.  In addition there has been no Institute of Medicine type Conflict of Interest Analysis.  And that is why I am asking for help from statisticians, biostatisticians and epidemiologists.  The task would entail a review of the literature prior to the introduction of these tests for evidence base of forensic applicability (there essentially is none) and a review of the literature peri-and post marketing of these devices to assess the reliability and credibility of the underlying methodology and ascertain the evidence-base.  The goal would be publication in both academic journals and presentation to the general public through media publication with the assistance of investigative journalists and other writers. The goal is to get the truth out about these tests and allow both the medial profession and public at large to awaken to the menace this presents to medicine, our society and our future.

 Lack of Evidence-Base, Bias and Conflicts of Interest:  Making the Data Fit the Hypothesis

I am no epidemiologist or statistician but as with pornography I know junk-science when I see it.  Almost all of these tests were introduced with little or no evidence-base and, as with most of their endeavors, they did it below board via loopholes and cutting corners.

The overwhelming majority of papers are small, methodologically flawed, non-randomized, non-blinded  retrospective studies in that appear to make the data fit the hypothesis.   The authors can invariably be linked to those profiting from the tests of the testing process ( the patent holder, doctors associated with the drug testing labs, ASAM or FSPHP, Robert Dupont, Greg Skipper, etc.)

 

Ethyl Glucuronide (EtG) was introduced in 1999 as a biomarker for alcohol consumption,¹ and was subsequently suggested as a tool to monitor health professionals by Dr. Gregory Skipper because of its high sensitivity to ethanol ingestion.²   

Described as the  “innovator of EtG as an alcohol biomarker,” Skipper and  Friedrich Wurst,  “convinced” NMS labs in Pennsylvania “to start performing EtG testing in 2002.

The study most often cited as 100% proof that there is 100% accuracy in EtG testing proving alcohol consumption involved a mere 35 forensic psychiatric inpatients in Germany that was published in 2003.³  

Shortly thereafter the Physician Health Programs began using it in monitoring doctors and other professional monitoring programs soon followed.

Laboratory Developed Tests -A Loophole to Avoid FDA Approval and Accountability

Up until the birth of the EtG tests used for forensic drug and alcohol monitoring had to go through the arduous, expensive and necessary FDA approval process.   The LDT pathway was designed to develop simple tests with little risk that have  low market potential (i;e. the cost of the normal FDA approval process would prohibit them from coming to market).  The LDT pathway was designed to improve patient care and help improve diagnosis and treatment. It was not designed for forensic tests.  LDT approval does not require in vivo testing.  It is essentially an honor system and to develop an LDT it is not even necessary to prove that the test is actually testing what it is purportedly testing for (validity).

So with little to no evidence base they introduced the EtG, had it developed and marketed as a LDT in collusion with unscrupulous labs, and then began using it on physicians being monitored by State PHPs. This then spread to other monitoring organizations in which there was a large power-differential between those ordering the tests and those being tested (criminal-justice, other professional monitoring programs).  These biomarkers have never been used in Federal Drug Testing, SAMHSA approved, DOT, and other organizations where unions or other organizations are present and looking out for the best interests of those being tested.

Another example of how this group removes accountability.  There has been essentially no oversight or regulation of LDTs.  Although there was a recent push for regulation of these tests the Drug and Alcohol Testing Industry Association lobby made sure that forensic tests would be exempt.

They then began publishing “research” on the EtG using the physicians being monitored as subjects. Many of the studies promoting the EtG and other biomarkers can be found  in  Journals that are linked to organizations that are linked to AA and were organized to educate the medical community.

 

These small, methodologically flawed studies amount to little more than opinion pieces but   This “evidence-base” is predominantly in biased journals published by biased medical “societies.  

The EtG was subsequently found to be so sensitive that it could measure incidental exposure to alcohol in foods, over the counter cold medications, mouthwash^4,5, hand sanitizer gel⁶, nonalcoholic beer⁷, and nonalcoholic wine.⁸  Sauerkraut and bananas have even been shown to cause positive EtG levels.⁹

The United States Substance Abuse and Mental Health Services Administration warned against using a positive EtG as primary or sole evidence of drinking for disciplinary or legal action.¹⁰  The Wall Street Journal in 2006 reported the problems with the EtG to the general public.¹¹   

As any rational authority would do, the majority of monitoring agencies abandoned the EtG after these flaws were revealed. The PHPs did not.  They continued to use the EtG on doctors uninterruptedly by telling them to avoid any products that could potentially contain alcohol; a ubiquitous substance in the environment. Since that time they have justified and rationalized (EtG)^{2,12 13}  use by sequentially raising cutoff levels from 100 to 250 to 500 to 1000 to 2000 to now unknown and adding other LDTs as “confirmation tests such as Ethyl Sulfate (EtS)^14,15 Phosphatidyl-Ethanol ( Peth)^{16 17} and other devices such as the Subcutaneous Remote Alcohol Monitoring Bracelet (SCRAM) and, their newest device the Cellular Photo Digital Breathalyzer (CPDB) that has recently been launched, just like the EtG with little to no evidence base other than a pilot study done by Greg Skipper and Robert Dupont.¹⁸ 

A  2013 article published in an ASAM incubated journal Alcoholism: Clinical and Experimental Research promotes the Phosphatidyl-ethanol (PEth ) test to confirm drinking.¹⁶  The study was done on physicians being monitored by the Alabama Physician Health Program who tested positive for EtG/EtS alcohol biomarkers. It is co-authored by Robert Dupont, Greg Skipper, and Friedrich Wurst and involved 18 subjects who tested positive for EtG/EtS of whom 7 claimed they did not drink.  After finding that 5 of the 7 tested negative for PEth they concluded that “positive PEth testing following positive EtG/EtS results confirms recent drinking.  Hard to wrap your head around the science in that one.Skipper is also using both Scram ankle bracelets and the CPDB monitoring in pilots in the Human Interventional Motivational Study (HIMS) Program that was developed in 2009 to “identify, treat and, eventually, re-certify airline pilots with substance abuse problems. 

 

The Cochrane Collaboration does systematic reviews of the literature using conscientious, explicit, and judicious criteria to in order to produce and disseminate only high quality and evidenced based health care, exclude bias, and enhance transparency. The Cochrane database is a current and evolving database that includes the accuracy of diagnostic tests and is internationally recognized as the standard in evidence based health care.  This benchmark for evidence based health care and systematic reviews, records just 5 controlled trials under the topic ethyl glucuronide.^8,19-21 These 5 studies represent the only high-quality evidence regarding EtG applying to EtG. Information provided by the five studies suggests the following, and only the following:

1. EtG and EtS measurements increase with alcohol ingestion.
2. The window of detection is shorter than what is commonly proposed (80 hours).
3. Individual values are variable both within and between subjects.
4. Non alcoholic wine can cause positive levels.

Notably, there are no studies that fit Cochrane Criteria, other than non-alcoholic wine, that look at the pharmacokinetics of EtG or EtS in terms of dose-response curves, cut-off levels, specificity drug and food interactions, or modes of ingestion.

SAMHSA notes that there is little research on PEth and that EtG, EtS, and PEth “do not have a strong research base,” and that “it is not known at this time how the test results might be affected by the presence of physical diseases, ethnicity, gender, time, or the use of other drugs. Until considerable more research has occurred, use of these markers should be considered experimental.”

Phosphatidylethanol (PEth), SCRAM, and the  yields no data as a test in the Cochrane library.

SAMHSA notes that there is little research on PEth and that EtG, EtS, and PEth “do not have a strong research base,” and that “it is not known at this time how the test results might be affected by the presence of physical diseases, ethnicity, gender, time, or the use of other drugs. Until considerable more research has occurred, use of these markers should be considered experimental.”

Evidence based medicine (EBM) can be defined as the conscientious, explicit, and judicious use of current best evidence in making decisions about the care of individual patients.²²

Medical progress and scientific advancement is occurring so fast that the volume of medical literature is expanding at a rate of greater than 7% per year.²³

Evidence based medicine is not restricted to randomized trials and meta-analyses. It involves tracking down the best external evidence with which to answer our clinical questions.²²  

Expert opinion is the lowest level of evidence available in the EBM paradigm.^24,25

Fortunately, the scientific method is a tool to help people progress toward the truth despite their susceptibilities to confirmation bias and other errors.²⁶

Unfortunately, due to a confluence of factors (including political) this has not been done.  But, unless we want a  future as envisioned by Robert Dupont and explained in the the ASAM White Paper on Drug Testing we need to act now.  This is not a “New Paradigm” but a “New Inquisition.”

1. Wurst FM, Kempter C, Seidl S, Alt A. Ethyl glucuronide–a marker of alcohol consumption and a relapse marker with clinical and forensic implications. Alcohol Alcohol. Jan-Feb 1999;34(1):71-77.
2. Skipper GE, Weinmann W, Thierauf A, et al. Ethyl glucuronide: a biomarker to identify alcohol use by health professionals recovering from substance use disorders. Alcohol Alcohol. Sep-Oct 2004;39(5):445-449.
3. Wurst FM, Vogel R, Jachau K, et al. Ethyl glucuronide discloses recent covert alcohol use not detected by standard testing in forensic psychiatric inpatients. Alcohol Clin Exp Res. Mar 2003;27(3):471-476.
4. Costantino A, Digregorio EJ, Korn W, Spayd S, Rieders F. The effect of the use of mouthwash on ethylglucuronide concentrations in urine. J Anal Toxicol. Nov-Dec 2006;30(9):659-662.
5. Reisfield GM, Goldberger BA, Pesce AJ, et al. Ethyl glucuronide, ethyl sulfate, and ethanol in urine after intensive exposure to high ethanol content mouthwash. J Anal Toxicol. Jun 2011;35(5):264-268.
6. Rosano TG, Lin J. Ethyl glucuronide excretion in humans following oral administration of and dermal exposure to ethanol. J Anal Toxicol. Oct 2008;32(8):594-600.
7. Thierauf A, Gnann H, Wohlfarth A, et al. Urine tested positive for ethyl glucuronide and ethyl sulphate after the consumption of “non-alcoholic” beer. Forensic Sci Int. Oct 10 2010;202(1-3):82-85.
8. Hoiseth G, Yttredal B, Karinen R, Gjerde H, Christophersen A. Levels of ethyl glucuronide and ethyl sulfate in oral fluid, blood, and urine after use of mouthwash and ingestion of nonalcoholic wine. J Anal Toxicol. Mar 2010;34(2):84-88.
9. Musshoff F, Albermann E, Madea B. Ethyl glucuronide and ethyl sulfate in urine after consumption of various beverages and foods–misleading results? Int J Legal Med. Nov 2010;124(6):623-630.
10. Administration SAaMHS. The role of biomarkers in the treatment of alcohol use disorders. In: Advisory SAT, ed2006:1-7.
11. Helliker K. A test for alcohol–and its flaws. The Wall Street Journal2006.
12. Wurst FM, Skipper GE, Weinmann W. Ethyl glucuronide–the direct ethanol metabolite on the threshold from science to routine use. Addiction. Dec 2003;98 Suppl 2:51-61.
13. Wurst FM, Alling C, Aradottir S, et al. Emerging biomarkers: new directions and clinical applications. Alcoholism, clinical and experimental research. Mar 2005;29(3):465-473.
14. Anton RF. Commentary on: ethyl glucuronide and ethyl sulfate assays in clinical trials, interpretation, and limitations: results of a dose ranging alcohol challenge study and 2 clinical trials. Alcoholism, clinical and experimental research. Jul 2014;38(7):1826-1828.
15. Hernandez Redondo A, Schroeck A, Kneubuehl B, Weinmann W. Determination of ethyl glucuronide and ethyl sulfate from dried blood spots. International journal of legal medicine. Jul 2013;127(4):769-775.
16. Skipper GE, Thon N, Dupont RL, Baxter L, Wurst FM. Phosphatidylethanol: the potential role in further evaluating low positive urinary ethyl glucuronide and ethyl sulfate results. Alcoholism, clinical and experimental research. Sep 2013;37(9):1582-1586.
17. Hahn JA, Dobkin LM, Mayanja B, et al. Phosphatidylethanol (PEth) as a biomarker of alcohol consumption in HIV-positive patients in sub-Saharan Africa. Alcoholism, clinical and experimental research. May 2012;36(5):854-862.
18. Skipper GE, Thon N, DuPont RL, Campbell MD, Weinmann W, Wurst FM. Cellular photo digital breathalyzer for monitoring alcohol use: a pilot study. European addiction research. 2014;20(3):137-142.
19. Hoiseth G, Bernard JP, Stephanson N, et al. Comparison between the urinary alcohol markers EtG, EtS, and GTOL/5-HIAA in a controlled drinking experiment. Alcohol Alcohol. Mar-Apr 2008;43(2):187-191.
20. Wojcik MH, Hawthorne JS. Sensitivity of commercial ethyl glucuronide (ETG) testing in screening for alcohol abstinence. Alcohol Alcohol. Jul-Aug 2007;42(4):317-320.
21. Sarkola T, Dahl H, Eriksson CJ, Helander A. Urinary ethyl glucuronide and 5-hydroxytryptophol levels during repeated ethanol ingestion in healthy human subjects. Alcohol Alcohol. Jul-Aug 2003;38(4):347-351.
22. Sackett DL, Rosenberg WM, Gray JA, Haynes RB, Richardson WS. Evidence based medicine: what it is and what it isn’t. BMJ. Jan 13 1996;312(7023):71-72.
23. Norwitz ER, Greenberg JA. Promoting evidence-based medicine. Rev Obstet Gynecol. Summer 2008;1(3):93-94.
24. Shaneyfelt TM, Centor RM. Reassessment of clinical practice guidelines: go gently into that good night. JAMA. Feb 25 2009;301(8):868-869.
25. Straus SE, Green ML, Bell DS, et al. Evaluating the teaching of evidence based medicine: conceptual framework. BMJ. Oct 30 2004;329(7473):1029-1032.