October 3, 2002
Mr. Robert L. Stephenson, II, MPH
Director, Division of Workplace Programs
CSAP
5600 Fishers Lane
Rockwall II, Suite 815
Rockville, MD 20857
Dear Mr. Stephenson:
The Drug and Alcohol Testing Industry Association (DATIA), an 1,100+ member national trade association representing the entire spectrum of service providers in the drug and alcohol testing industry, has become concerned about the number of challenges to drug test results in regards to the specimen validity testing guidelines. These challenges have been made by persons who appear to have naturally provided a specimen that meets the “substituted” criteria (creatinine < 5mg/dl and specific gravity <1.002 or > 1.020) established by your agency. DATIA has researched this issue and believes that there is sufficient information warranting the need for further studies to establish the criteria for a “substituted” specimen. Furthermore, we are disheartened that much of this information was presented to your office during the formal comment period by numerous organizations, however, no further studies were conducted, and your office continues to push for the release of the final guidelines.
In your agency’s February 14, 2000 NLCP: State of the Science Update #1 – Urine Specimen Validity Testing: Evaluation of the Scientific Data Used to Define a Urine Specimen as Substituted, you state that “Our extensive review of the scientific literature has shown that there were no cases meeting the substituted specimen creatinine/specific gravity criteria in both the medical evaluation population and substance abuse population. Additionally, there were only a small number of either low creatinine or specific gravity test values even in the substance abuse population. These findings, taken together provide the realistic, scientific basis for the selected substituted specimen criteria.” It was not mentioned, however, that only a few of the studies actually studied both creatinine and specific gravity, and that only a small sampling of the studies were designed to study water loading.
DATIA believes that the “substituted” criteria needs to be reevaluated for the following reasons: (1) the clinically accepted reference ranges for normal urine referenced in your basis for the “substituted” criteria were disproved by the studies you referenced and by a study performed by the Department of Transportation (DOT); (2) studies exist, but were not evaluated by your office, on the effects of factors such as altitude, menstrual cycle, etc. on the body’s fluid balance and urine output, (3) it has been shown that the variance in creatinine and specific gravity measurements by HHS certified laboratories can vary as much as 0.001 for specific gravity and 2.2 for creatinine – a variance that could have caused specimens in the referenced studies to be reported as “substituted”. I will elaborate on each of these reasons illustrating the faults with the current “substituted” criteria.
According to the document NLCP: State of the Science Update #1 – Urine Specimen Validity Testing: Evaluation of the Scientific Data Used to Define a Urine Specimen as Substituted the clinically accepted reference ranges for normal random urine specimens are listed as 1.002 – 1.030 for specific gravity and 37 – 300 mg/dl for creatinine in women and 44 - 250 mg/dl in men. However, in the data listed in Table 1 of the Department of Transportation’s (DOT) study entitled Paired Measurements of Creatinine and Specific Gravity After Water Loading, only 3 creatinine measurements out of 56 within this range. Of the 95% below the “clinically accepted reference range”, 31% were well below the level within 1 – 3 hours after the study was initiated. For example, in the first hour a female gave a specimen with a creatinine measurement of 12.6 mg/dl, which is just one-third of the lowest clinically accepted range.
The data results in Table 1 of the DOT study also show that 27% of the measurements were below the clinically accepted range for specific gravity. Again, 13% of these reported measurements were from specimens provided within the first three hours of the study. Since drinking up to 40 ounces of water is not considered high by any standards (recognized minimum recommended daily water intake is eight 8oz glasses or 64 oz.), it would seem that any results obtained within the first three hours of the study would be considered “normal”. The same would apply to all results obtained in the study since 80 oz. (the full amount consumed over the study’s six hour period) is only two 8oz. glasses of water above the recognized minimum recommended amount of daily fluid intake.
Furthermore, HHS states that none of reviewed studies used to determine the specimen validity criteria contained specimens meeting both of the criteria for a substituted specimen. It should be noted, however, that many of the studies that examined only creatinine levels included specimens that had a creatinine reading of 5.1 mg/dl or lower, and many studies that studied only specific gravity included specimens that had a specific gravity reading of less than 1.002. The fact that the studies did not measure both criteria is not evidence enough to say, “our extensive review of the scientific literature has shown that there were no cases meeting the substituted specimen creatinine/specific gravity in both the medical evaluation population and substance abuse population”.
The second reason warranting additional studies before implementing “substituted specimen” criteria is that many studies exist, but were not evaluated by your office, on the effects of factors such as altitude, menstrual cycle, diet, etc. on the body’s body fluid balance and urine output. Studies have been published on the decline of creatinine and urea clearances in women during mid-menstrual cycle. (Mid-menstrual cycle decline in creatinine and urea clearances. Nephron 67: 158-66 (1994)). In addition, creatinine levels are related to muscle mass, and therefore would be considered to be lower in women with low levels of muscle mass and smaller weights.
Of important notice in relation to the numerous number of airline flight attendants that have submitted normal urine specimens, which have been reported as “substituted” are the published studies on the effect of high altitude on body fluid metabolism. (Body fluid and energy metabolism at high altitude. Handbook of Physiology 1277-1285) Specifically, body responses to high altitude (cabin pressure on airplanes is equivalent to the air pressure for altitudes between 5,000 M and 8,000 M) include increased water loss and diuresis. Combine this phenomenon with the decreased humidity (10-20%) in airline cabins and the increased water intake by those on board to counteract the dry atmosphere, and a unique situation is created whereby multiple factors, all of which are normal, can lead to an exceptionally dilute specimen.
The final reason to be considered is that of a laboratory’s coefficient of variation. Since it has been shown through scientific studies that a person can legitimately provide a specimen that has a creatinine of 5.1 mg/dl and a specific gravity of 1.001, to set the criteria at < 5.0 mg/dl and <1.002 leaves no room for laboratory error. Since the accepted error rate for the National Laboratory Certification Program (NLCP) proficiency testing is 20%, it is hard to believe that the accepted error rate for specimen validity testing is 0%. In comments received through the comment period, at least one laboratory reported that their error rate for creatinine testing is between 2.5% and 5%. Using these error rates, three specimens in the DOT study would have been reported as “substituted” even though collected as part of a controlled study. Other comments show that specific gravity measurements can vary as much as 0.001 and creatinine measurements can vary as much as 2.2 mg/dl. Again, these small variations in accuracy will mean the difference between a legitimate specimen being considered normal or being reported as “substituted”.
We hope that your office decides to do the right thing and further evaluate the criteria for “substituted” specimens before proceeding with implementing the guidelines. While only a small percent of specimens are reported as “substituted” each year, for those employees that are incorrectly categorized as a “cheater” this means their loss of a job and their livelihood. Sacrificing some for the better good of the whole should not be acceptable and all possible reasons for legitimately submitting a specimen categorized as “substituted” under the specimen validity guidelines should be explored so that criteria will be established that does not mistakenly report a legitimate specimen as “substituted”.
Due to the fact that it has been shown that a normal person can submit a specimen that is on the threshold of the ?substituted? criteria, and that with the documented laboratory coefficient of variation such a specimen could be incorrectly categorized as ?substituted?, we implore you to further research the issue before proceeding with publishing your final Validity Testing Guidelines. DATIA fears that, should you proceed with the publishing and implementation of the Validity Testing Guidelines, additional drug-free employees will be incorrectly categorized as ?cheaters? and suffer the consequences without any means of clearing their names. Such an action would be irresponsible and extremely detrimental to the public’s perception of drug testing programs. Should you have any questions on these comments, I can be reached at 800-355-1257 or lshelton@datia.org.
Sincerely,
Laura E. Shelton
Executive Director
CC: Secretary Tommy G. Thompson, HHS
Secretary Norman Y. Mineta, DOT
Kenneth Edgell, DOT
Members of the Senate Committee on Health, Education, Labor, and Pensions
Members of the House Committee on Education and the Workforce
