toxicology testing is it a good fit for your …toxicology testing… is it a good fit for your...

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CRI and COLA do not endorse, directly or indirectly, the presentations given at this conference or the products or services provided by the exhibiting vendors. Presentations are intended to be free of bias. The use of any particular product is for demonstration purposes only, and does not imply an endorsement of the product by the presenter or the sponsors of the symposium. © 2017 CRI

Toxicology Testing… Is it a Good Fit for Your Laboratory?

Rebecca Kenner, BA, MT, DLM(ASCP)

Leigh Ann Smith, BS, MLS(ASCP), CLS

Global Analytical Development

DESCRIPTION:

Are you considering expanding your lab services into toxicology testing? With the epidemic of overdoses from Opioid abuse and the recommendation by the CDC to screen and monitor patients prescribed opioid pain medication, Urine drug testing is being implemented across the country. Urine drug testing is being utilized by not only pain management and substance abuse clinics but by physician office laboratories to meet the monitoring standards. This presentation will briefly point out the need for drug testing. It will describe how the facilities use urine drug testing to meet best practice standards. The difference between POCT, immunoassay screening and LCMS/MS testing will be discussed. And finally, this presentation will explain the implementation process focusing on the compliance standards from personnel to validation.

OBJECTIVES:

At the end of the session, participants will be able to:

Describe toxicology testing

Summarize important needs for drug screening

Outline how the lab fits into best practices in pain management and substance abuse monitoring

Describe how the testing is done using immunoassay testing and LCMS/MS confirmation testing

Focus on compliance when implementing toxicology services

Thursday April 6, 2017

FOR EXTERNAL USE. PRINT & DISTRIBUTION PERMITTED.

Toxicology Testing…Is this a good fit for your laboratory?

Presented by Rebecca Kenner BA, MT, DLM(ASCP) and Leigh Ann Smith BS, MLS(ASCP), CLS

CRI Symposium 2017


Who We Are

Global Analytical Development has a proven track record of establishing and supporting successful licensed laboratories operating within compliance guidelines. We provide consulting services to support sustainable, compliant-driven lab operations.

Credentialed technical consultants

Application, licensure, and accreditation

Laboratory set up

Quality control procedures

Audit and inspection support

1

Graph created by Alere Toxicology.


Objectives

Define toxicology testing

Describe the need for urine drug testing

Understand the differences between various testing methodologies

Compliance requirements for high complex testing

2

FOR EXTERNAL USE. PRINT & DISTRIBUTION PERMITTED.FOR EXTERNAL USE. PRINT & DISTRIBUTION PERMITTED.

What is Toxicology Testing?

It is the measurement and interpretation of concentrations of drugs and other toxic substances in human biological fluids for the purpose of patient care.


History


History

For thousands of years, opiates have been used to relieve pain. It was originally derived from the opium poppy.

Morphine is the active substance. It was named after Morpheus, the Greek god of dreams.

5

Papaver somniferum


History (cont’d)

During the 16th century, early chemists created laudanum, an opium tincture prepared in an alcoholic solution (brandy).

By the 19th century, it was available in the pharmacy or general store.

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Graphic: Library of Congress, http://www.loc.gov/pictures/item/92512903/


History (cont’d)

Infants were introduced to opiates through breast milk.

Harassed babysitters and overworked parents found opium-based preparations were a dependable way to keep their children happy and docile.

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Graphic created by Alere Toxicology.


History (cont’d)

In 1830 codeine, a naturally-occurring methylated morphine, was first isolated to replace raw opium for medical purposes. It was primarily used as a cough remedy.

Later in the 19th century, morphine was extracted in its pure form.

In 1874 chemists also developed heroin in an effort to create something less addictive than morphine — but they ended up developing something with twice the addictive qualities.

In 1898, heroin was marketed as a non-addictive cough suppressant.

The U.S. banned opium in 1905, and the following year the Pure Food and Drug Act was passed, requiring content labeling on all food and drug products.

In 1924 the Heroin Act banned the manufacture, importation, and possession of heroin.

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Recent History

By the late 20th century, a new breed of painkillers hit the market —synthetic opiates which mimic the body’s natural painkillers. Common names include Vicodin (1984), OxyContin (1995), and Percocet (1999).

Since 1999, prescriptions for opioid pain medication have quadrupled.

This leads us to where we are today…

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The Opioid Epidemic


Statistics

From 2000 to 2015, more than half a million people died from drug overdoses.

Since 2000, the rate of deaths from overdoses has increased 137%.

Including a 200% increase in the rate of overdose death involving opioids.

In 2014, an estimated 1.9 million people had an opioid use disorder related to prescription pain relievers and an estimated 586,000 had an opioid use disorder related to heroin use.

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Statistics

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die everyday from an opioid overdose (that includes prescription opioids and heroin).

91Americans



Statistics

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Centers for Diseases Control and Prevention, IMS, National Prescription Audit (NPA™), 2012. https://www.cdc.gov/vitalsigns/opioid-prescribing/infographic.html/


Overdose Death Rates

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1999 2014

Centers for Diseases Control and Prevention, National Vital Statistics System. https://blogs.cdc.gov/nchs-data-visualization/drug-poisoning-mortality/


Increase in Regulatory Support and Funding

Protecting Our Infants Act of 2015

CARA – Comprehensive Addiction Recovery Act

Medicaid expansion for Substance Use Disorders (SUD)

New guidelines for testing and monitoring

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$


Federal Support

The Centers for Disease Control and Prevention (CDC) released new opioid guidelines on March 15, 2016.

This new guideline is for primary care providers—who account for prescribing nearly half of all opioid prescriptions—treating adult patients for chronic pain in outpatient settings. It is not intended for guiding treatment of patients in active cancer treatment, palliative care, or end-of-life care.

Urine Drug Testing (UDT) plays import role in managing prescription opioid use.

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CDC Recommendations

When prescribing opioids for chronic pain, clinicians should use urine drug testing before starting opioid therapy.

Consider urine drug testing at least annually to assess for prescribed medications as well as other controlled prescription and illicit drugs.

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New Guidelines

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Pain management Addiction treatment

The National Academy of Clinical Biochemistry

Presents LABORATORY MEDICINE PRACTICE GUIDELINES

Using Clinical Laboratory Tests to Monitor Drug Therapy

in Pain Management Patients



Why is Drug Testing Necessary?

19

Statistics

National drug epidemic

Changing regulations

Increased government support

National organizations: new guidance and recommendations:CDC1, ASAM2, SAMSHA3, NIDA4, and AACC5

1. Centers for Disease Control and Prevention (CDC)2. American Society of Addiction Medicine (ASAM)

3. Substance Abuse and Mental Health Services Administration (SAMSHA)4. National Institute on Drug Abuse (NIDA)

5. American Association for Clinical Chemistry (AACC)


Where is Drug Testing Relevant?

Primary care

Pain management

Substance abuse– Rehabilitation

– Detoxification

– Addiction medicine

Other– Rural health clinics

– Obstetrics (OB)

20FOR EXTERNAL USE. PRINT & DISTRIBUTION PERMITTED.


Use of UDT in Primary Care

Unexplained symptoms or unexpected response to treatment

Evaluating patient in psychiatric care for substance abuse issues before prescribing psychoactive medications

Identification of potential substance abuse problems in women who are pregnant or planning on becoming pregnant

Identifying patients with possible substance abuse issues

Monitoring patients in substance abuse programs

Ensuring patient safety prior to surgery or other invasive procedure, to prevent medication interactions

Managing patients with prescribed opioids for chronic pain

Monitoring potentially addictive prescription use (sedatives, tranquillizers and medication for attention deficient disorders)

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Use of UDT in Pain Management

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Drug testing in pain management clinics is used to determine:– Whether the patient is taking the pain medication as prescribed

– Whether the patient is abusing other substances

Opioids are drugs that produce analgesia through interaction with opioid receptors found in the central nervous system.

Benzodiazepines are psychoactive drugs that are often taken by chronic pain patients to improve sleep, relax musculature, and relieve anxiety that may be attributed to or exacerbate the sensation of pain.


Substance Use Disorders (SUD)

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SAMSHA’s recommended treatment plan for drug testing in Substance Use Disorders (SUD):

– Baseline drug levels are a component of the initial assessment of a patient being evaluated for a diagnosis of an SUD

– Screen to prevent potential adverse effects of pharmacotherapy (e.g., opioid screen prior to starting naltrexone)

– A way to monitor the patient’s use of illicit substances (including illegal drugs and non-medical use of prescription drugs)

– Adherence to pharmacotherapy treatment for SUDs and a way to assess the efficacy of the treatment plan (i.e., level of care)


Types of Opioid Pain Medications

Natural (derived from the opium poppy):

– Codeine and Morphine

Semi-Synthetic:

– Hydromorphone, Hydrocodone, Oxycodone, Oxymorphone, and Heroin

Synthetic:

– Fentanyl, Methadone, Tramadol, Propoxyphene, Buprenorphine, and Meperidine

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Examples of Metabolism of Opioids

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Codeine

Hydrocodone

Oxycodone

Morphine

Hydromorphone

Oxymorphone

6-AM Heroin

Not comprehensive pathways, but may explain presence of apparently unprescribed drugs

t ½ = 25-30 mins t ½ = 3-5 mins



Major Opioid Metabolites

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Opioid Inactive metabolitesAcive metabolites indenticalto pharmaceutical opioids

Active metabolites that are not pharmaceutical opioids

Morphine Normorphine Hydromorphone1 Morphone-3-G glucuronideMorphone-6-G glucuronide

Hydromorphone Minor metabollites None Hydromorphone-3-glucuronide

Hydrocodone Norhydrocodone Hydromorphone None

Codeine NorcodeineHydrocodone

MorphineNone

Oxycodone None Oxymorphone Noroxycodone

Oxymorphone Oxymorphone-3-glucuronide None 6-Hydroxy-oxymorphone

Fentanyl Norfentanyl None None

Tramadol Nortramadol None O-desmethyltramadol

Methadone2-Ethylidene-1,5-dimethyl-3,3-

diphenylpyrrolidine2-Ethyl-5-methyl-3,3-diphenylpyrroline

None None

Heroin Normorphine Morphine 6-Monoacetylmorphine

1. Only very low levels are seen in the urine: less than 11% for hydrocodone after codeine administration and less than 2.5% for hydromorphone after morphine administration.



Major Benzodiazepines Metabolites

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Benzodiazepines(generic name)

Trade name exampleDuration of parent

drug activityMetabolite examples

found in urine

Alprazolam Xanax® Intermediate Alpha-hydroxyalprazolam

Chlordiazepoxide Librium® Pro-drug Nordiazepam

Clonazepam Klonopin® Intermediate 7-aminoclonazepam

Diazepam Valium® Long-actingNordiazepam and Temazepam, both of

which metabolize into Oxazepam

Flunitrazepam Rohypnol® Intermediate 7-aminoflunitrazepam

Flurazepam Dalmane® Short-actingDesalkylflurazepam,

2-hydroxyethylflurazepam

Lorazepam Ativan® Short-acting Lorazepam glucuronide

Midazolam Versed® Short-acting Alpha-hydroxymidazolam

Nordiazepam Long-acting Oxazepam

Oxazepam Serax® Short-actingOxazepam glucuronide

(liberated by hydrolysis treatment)

Prazepam Centrac® Long-acting Nordiazepam

Temazepam Restoril® Intermediate Oxazepam

Triazolam Halcion® Short-acting Alpha-hydroxytriazolam




Use and Detection

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methodone3-6 days

oxycodone2-4 days

codeine/morphine2-3 days

chronic use20-30 days

beginning2-4 days

6-AM4-12 hours

methamphetamine3-4 days

long-acting30 days

long-acting21 days

Ethyl glucuronide> 72 hours

single use2-8 days

hours

heroin40 mins

amphetamine1-2 days

short-acting3 days

short-acting1 day

7-12 hours

Marijuana metabolite

Cocaine

Opioidmetabolites

Amphetamine

Benzodiazepines

Barbiturates

Alcohol


If It Could Only Be This Easy…

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Drug Screening


Overview of Drug Testing

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Drug screening

– Detects chemical classes in a drug sample

– Qualitative or semi-quantitative

– Performed using immunoassay principles

– Screening can be performed as POCT cup or by instrumentation

Confirmation and Quantitation

– Detects and identifies the actual drug compound present in a sample

– Quantifies the amount of target compound present in the sample

– Performed using gas chromatography mass spectrometry (GC-MS) or liquid chromatography tandem mass spectrometry (LC-MS/MS)


Why Bother with Drug Screening?

Provides timely results for clinicians.

Which improves patient care and communication by managing the misuse and diversion risks associated with select medications.

To verify patient self-report of medication history.

– Is a prescribed drug present?

– Is anything else unexpectedly present?

To encourage or reinforce healthy behavioral change, or sometimes as a requirement of continued treatment.

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Drug Screening Tests

Screening tests are based on immunoassay techniques.

The majority of POC screening tests use test strips.

– Higher incidence of false positives

– Limited test panel availability

– Inconsistent interpretation of result

Instrument screening tests use liquid reagents.

– More selective, i.e. fewer false positives

– Larger number of drug classes available, including “newer” drugs such as carisoprodol (SOMA®), fentanyl, zolpidem (Ambien®), and Spice/K2

– Consistent results

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Point of Care Testing (POCT)


Point of Care Testing (POCT)

POCT refers to any testing performed outside the traditional laboratory, such as a physician office, rehabilitation facility, emergency department, or urgent care.

Many clinical rapid screening devices are categorized as CLIA-Waived and may be used by laboratories with a CLIA certificate.

Instrumentation is available and can be considered point of care:– It is not considered waived.

– It follows non-waived compliance criteria.

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Pros Cons

Convenient and portable Cost is higher

Reduced wait time and immediate clinician consultation

Minimum use of quality assurance and control processes

Fast turnaround time Less sensitive & less specific than analyzer with reagents, resulting in false positive or false negative

No special personnel requirements Some drugs have higher cutoffs on the waived method

Minimal CLIA requirements Limited test panel to 12 drug classesLimited data management systems


Pros and Cons of Using Waived Drug Screening Systems


Screening Instrumentation


Advantages of Screening Instrumentation

Consistency of patient results.

Standardization of testing procedure:– Same sample size

– Instrument monitored timing

– Daily quality control

Higher sensitivity and specificity.

Broader test menu.

Pertinent patient cutoffs.

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Test Menu Available

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Sample Validity pH

Chromate

Creatinine

Oxidant

Nitrite

Specific Gravity

Drug Screening 6-AM

Alcohol

Amphetamine

Barbiturates

Benzodiazepines

Benzoylecgonine(Cocaine Metabolite)

Buprenorphine

Cannabinoids (THC)

Carisoprodol

EDDP (Methadone Metabolite)

Ethyl Glucuronide

Fentanyl

Ketamine

Meperidine

Methadone

Methamphetamine

Opiates

Oxycodone

Phencyclidine (PCP)

Propoxyphene

Synthetic Cannabinoids

Tapentadol

Tricyclic Antidepressants (TCA)

Tramadol

Zolpidem


Enzyme Immunoassays (EIA)

EIAs are biochemical tests that measure the concentration of a substance in a biological liquid (typically serum, plasma, saliva and urine) using the reaction of an antibody or antibodies in the reagent to its antigen (target drug) in the sample.

“Lock and Key” type model reaction.

In drug screening, antibodies target a specific analyte(or drug class).

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Adulteration


Adulterants

A substance a patient adds to the specimen to mask the presence of the drug or drug metabolite in the specimen.

Usually people try to cheat drug testing by three different ways:

Substituting their urine with synthetic urine or drug-free urine purchased from a clandestine source.

Drinking a commercially available product to flush out drugs (overhydration rapidly fills the bladder with water to dilute the drugs and metabolites).

Adding an adulterant in vitro to the urine specimen after collection.

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Specimen Validity Tests

Specimen validity tests determine whether a urine specimen has been diluted, adulterated or substituted to obtain a negative result.

It is not required in the clinical settings, but in their recent publication LABORATORY MEDICINE PRACTICE GUIDELINES: Using Clinical Laboratory Tests to Monitor Drug Therapy in Pain Management Patients, The National Academy of Clinical Biochemistry suggests validity testing be performed prior to testing for drugs in the urine sample. Do not test sample if adulteration is suspected.

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Types of Validity Testing

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pH: specimen adulteration should be suspected if the pH level is less than 3.0 or greater than 11.0

Creatinine: If the creatinine is less than 20 mg/dL, specific gravity testing should be performed

Specific gravity: Only specimens whose urine creatinine is less then 20 mg/dL need to be reflexively tested. Specimens with a low creatinine and an abnormal specific gravity may be reported as dilute, invalid or substituted depending on the laboratory’s reporting policy

Oxidants: detects the presence bleach, nitrite, chromate, iodate and peroxidase. These are common ingredients of commercially available adulterants used to inhibit or mask the screening results

Nitrite: a sample is considered adulterated if the nitrite concentration is > 500 mg/L

Urine temperature: 90.5 – 98.9 °F


Confirmation Instrumentation


When to Confirm

46

To detect specific drugs that cannot be identified on standard immunoassays

The presence of “unexpected urine drug test results,” according to the new CDC guidance

To be able to identify between drugs in a class


Confirmation Testing

47

Generally performed using LC-MS/MS technology

Turnaround time is usually 3-5 days from collection

Results are specific for the drug and drug metabolite

High specificity and sensitivity

Results are quantitative, high complex, and considered laboratory-developed testing


Regulatory Compliance


Compliance Requirements

49

Personnel standards– High complexity requirements

Validation standards– Lab developed testing


Personnel


High Complexity – Personnel

51

PositionLaboratory Director

Requirements

1. Licensed MD1/ DO2/ DPM3 AND certified in anatomic or clinical pathology OR 1 year of lab training during medical residency OR 2 years experience directing or supervising high complexity testing

2. Doctoral degree in laboratory science AND certified by an HHS4-approved board OR prior to 02/24/2003, served as Lab Director AND 2 years lab training or experience AND 2 years experience supervising or directing high complexity testing

1. Doctor of Medicine (MD)2. Doctor of Osteopathic Medicine (DO)

3. Doctor of Podiatric Medicine (DPM)4. U.S. Department of Health & Human Services (HHS)



52

PositionTechnical Supervisor

Requirements

1. Licensed MD/DO/DPM or PhD AND certified in clinical pathology OR 1 year lab training or experience in the high complexity testing specialties performed

2. Master’s degree in lab science AND 2 years lab training or experience in the high complexity testing specialties performed

3. Bachelor’s degree in lab science AND 4 years lab training or experience in the high complexity testing specialties performed

4. Additional COLA requirement:must have 1 year of LC-MS/MS hands-on experience



53

PositionGeneral Supervisor

Requirements

1. Qualified Lab Director or Technical Supervisor of high complexity testing

2. Licensed MD/DO/DPM, or have a Doctoral, Master’s, or Bachelor’s degree in lab science AND 1 year laboratory training or experience in high complexity testing

3. Qualified as Testing Personnel for high complexity testing AND at least 2 years laboratory training or experience in high complexity testing

4. Previously qualified as General Supervisor on or before 02/28/1992



54

PositionTesting Personnel

Requirements

1. Licensed MD/DO/DPM

2. Doctoral, Master’s, Bachelor’s or Associate’s degree in laboratory science

3. Have education equivalent to an Associate’s degree AND graduated from a clinical laboratory training program OR have 3 months experience in each specialty of high complexity testing performed

4. Prior to 04/24/1995, High School graduate or equivalent AND graduated from an HHS-approved lab training program OR completed military Medical Lab Specialist (50 week) course

5. Prior to 04/24/1995, High School graduate or equivalent AND documentation of training for high complexity testing AND if training before 01/19/93, on-site supervision is required when high complexity testing is performed


Validation Requirements


CLIA1 Standard

56

D5423

493.1253 (b)(2) Establishment of performance specifications. Each laboratory that modifies a test system cleared for U.S. market, or introduces a test system not subject to clearance or approval (including methods developed in-house and standardized methods such as text book procedures), or uses a test system in which performance specifications are not provided by the manufacturer must, before reporting patient test results, establish for each test system the performance specifications for the following performance characteristics, as applicable.

1. Clinical Laboratory Improvement Amendments (CLIA)


CLIA Validation Requirements

57

Requirements Accuracy

Precision

Reportable Range

Sensitivity

Specificity

Any other performance characteristics required for verifying test performance

Reference Range (not applicable for drug detection)

Determination of calibration and QC frequencies

COLA Criteria VER1 5

VER 6

VER 7

VER 9

VER 10

VER 11

VER 8

VER 12

1. Verification of performance standards (VER)


CLIA Validation Requirements

58

Must start with a

writtenvalidation

plan


Validation Plan

59

A validation plan should include: All experiments required for method validation

Detailed instructions describing how the experiments will be performed

Supplies and reagents needed

Calibrator and QC number and concentrations

Acceptability criteria for evaluation of raw data (this should be based on appropriate guidelines)


Method Validation:High Complexity Testing – Qualitative


Validation Requirements – Qualitative

AccuracyVerified by testing samples with known values and comparing results

PrecisionVerifies that results can be repeated on day-to-day, run-to-run, and within runs

Analytical sensitivity The lowest concentration that can be differentiated from the cutoff point for a positive result

SpecificityThe ability to find the presence of a target compound in a sample

Sample storage stability (room temp, refrigerated, frozen)

Interfering substances

Carryover assessment

61


Method Validation:High Complexity Testing – Quantitative LC-MS/MS


Specific Components of the LC-MS/MS1

Method Validation

63

AccuracyVerified by testing samples with known values and comparing results

Precision

LOQ2 and LOD3 Determinations (S/N ratio of the LLOQ 10:1)

Linearity

Carryover Assessment

Matrix Effect (Ion suppression)

Cross Talk Evaluation of structurally-related molecules

Interference Testing

Ion Ratio Monitoring

Stability

1. Liquid chromatography tandem mass spectrometry (LC-MS/MS) 2. limit of quantitation (LOQ)

3. limit of detection (LOD)


Primary References for LC-MS/MS Method Validation

64

CLSI1 Guidelines Liquid chromatography

tandem mass spectrometry (LC-MS/MS) methods

Mass spectrometry in the clinical lab

Stability of in-vitro diagnostic reagents

CLSI Document C62-A

C50-A

EP25-A

1. Clinical & Laboratory Standards Institute (CLSI)


Primary References for LC-MS/MS Method Validation (cont’d)

65

CLSI Guidelines Precision

Accuracy

Analytical measurement range

LoB, LoD, LLoQ

Total analytical error

Interference testing

CLSI Document EP05-A3

EP09-A3

EP06-A

EP17-A2

EP21-A

EP07-A2


Additional References for Method Validations

66

FDA Guidance for Industry: Bioanalytical Method Validation, May 2001

CLIA-Compliant Analytical Method Validation Plan and Template for LRN-C Laboratories, December 2013

Scientific Working Group for Forensic Toxicology (SWGTOX) Standard Practices for Method Validation in Forensic Toxicology, 2013


Evaluation of the Validation Data

67

Once the validation experiments have been completed you must evaluate the data and compile it in a format that demonstrates you have met your acceptability criteria that is stated in your validation plan, for all components of the plan.

The validation must be approved by your Technical Supervisor and Lab Director.


Additional Compliance Requirements

68

Must have detailed procedures for reagent preparation. Include: controls, calibrators, solvents, internal standard working solutions, and hydrolysis reagent. (APM 6, MA 1)

Procedure for the validation of new lots of in house prepared reagents, controls, and calibrators. (APM 6)

Documentation process to record validations of reagents and standards use. (APM 7)

Instructions for performing calibrations. Must include acceptability limits. Criteria for dropping calibration points. (APM 7)


Additional Compliance Requirements (cont’d)

69

QC procedure defines limit of acceptability, number, type, frequency of performance. Review criteria. (APM 8)

Procedure for corrective actions for QC or calibration failure. (APM 9)

Establish a maintenance program and documentation process to record required daily function checks and required maintenance. (MA 17)

Step by step instructions for performing testing. Must include sample prep and criteria for interpreting test results. (APM 10)


Additional Compliance Requirements (cont’d)

70

Written instruction for specimen collection, labeling and conditions regarding specimen transport available for your clients. (PRE 11)

Written policies and procedures for collection, handling, transportation, and storage of specimens. (PRE 12)

Proficiency Testing. Enrollment in a module that is consistent with type of testing performed. If performing quantitative testing don’t enroll in a qualitative module. Split sample testing procedure to cover drugs not included in PT. (PT 4)


Summary

71

The opioid overdose epidemic is real.

Pain management and rehabilitation are not the only practices that monitor drug use. Any practitioner who prescribes drugs is required to monitor.

The laboratory testing is a integral component in monitoring patient compliance. This can be done through screening and confirmation testing.

All testing must follow CLIA guidelines.

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Anyquestions?


References

73

CDC Morbidity and Mortality Weekly Report (MMWR): Increases in Drug and Opioid Overdose Deaths — United States, 2000-2014https://www.cdc.gov/mmwr/preview/mmwrhtml/mm6450a3.htm

SAMSHA https://www.samhsa.gov/disorders/substance-use

SAMSHA Technical Assistance Publication 32

CDC Guidelines for Prescribing Opioids for Chronic Pain, US 2016http://www.cdc.gov/mmwr/volumes/65/rr/rr6501e1.htm

American Society of Addiction Medicinehttp://www.asam.org/docs/default-source/public-policy-statements/1drug-testing---clinical-10-10.pdf

AACC: How People Try to Beat Drug Testing https://www.aacc.org/publications/cln/articles/2015/february/drug-testing.aspx

The National Academy of Clinical Biochemistry, Laboratory Medicine Practice Guidelines: Using Clinical Laboratory Tests to Monitor Drug Therapy in Pain Management Patients, July 2016.


Waived Testing References

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For a list of waived tests sorted by analyte name, visit the FDA website at: http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfClia/analyteswaived.cfm

For a list of waived tests sorted by the test categorization date and by the test system name, visit the FDA website at: http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfClia/testswaived.cfm


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toxicology testing is it a good fit for your …toxicology testing… is it a good fit for your...

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