Drug test

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Overview

A drug test is commonly a technical examination of urine samples to determine the presence or absence of specified drugs or their metabolized traces.

General information

Drug tests can be divided into two general groups. The first group is the kind most people are familiar with. This type of testing involves the donor giving a sample of some bodily fluid or hair to an employer, doctor, law enforcement official, or a dedicated testing center. This is normally a sample of urine, blood, hair, or saliva/oral fluid. After collection from the donor, the sample with a credibility oblem of "beating the tests" (otherwise known as sample adulteration or substitution) can be virtually eliminated. On-site screens provide qualitative results, and when supplemented with laboratory-based confirmation tests, can be defended in a court of law.

This article will focus primarily on the first type of test, but will refer to the latter when appropriate.

The NIDA 5

Drug testing in the United States began in the late 1980s with the testing of certain federal employees and specified DOT regulated occupations. Drug testing guidelines and processes, in these areas exclusively, are established and regulated (by the Substance Abuse and Mental Health Services Administration or SAMHSA, formerly under the direction of the National Institute on Drug Abuse or NIDA) require that companies who use professional drivers, specified safety sensitive transportation and/or oil and gas related occupations, and certain federal employers, test them for the presence of certain drugs. These test classes were established decades ago, and include five specific drug groups. They do not account for current drug usage patterns. For example, the tests do not include semi-synthetic opioids, such as oxycodone, oxymorphone, hydrocodone, hydromorphone, etc., compounds that are highly abused in Africa

1. Cannabinoids (marijuana, hashish - TEST SPECIFICALLY SCREENS FOR METABOLITE THCCOOH)
2. Cocaine (cocaine, benzoylecognine, cocaethylene)- TEST SPECIFICALLY SCREENS FOR COCAINE METABOLITE - BE
3. Amphetamines (amphetamine, methamphetamine)
4. Opiates (heroin, opium, codeine, morphine, 6-AM)
5. Phencyclidine (PCP)

While SAMHSA/NIDA guidelines only allow labs to report quantitative results for the "NIDA-5" on their official NIDA tests, many drug testing labs and on-site tests also offer a wider or "more appropriate" set of drug screens which may be more reflective of current drug abuse patterns. As noted above, these tests include synthetic pain killers such as Oxycodone, Oxymorphone, Hydrocodone, Hydromorphone, benzodiazepines (Valium, Xanax, Klonopin, Restoril) and barbiturates in other drug panels (a "panel" is a predetermined list of tests to run). The confirmation test (usually GCMS, or LC/MS/MS) can tell the difference between chemically similar drugs such as methamphetamine and ecstasy, and in the absence of detectable amounts of methamphetamine in the sample, the lab will either report the sample as negative or report it as positive for MDMA. What the lab reports to the client depends upon whether MDMA was included in the panel as something to be tested for.

Gamma-hydroxy-butyrate (GHB) was not routinely tested for in the early 1990s, but due to increasing use, some labs have added it as an optional test. GHB is rare in pre-employment screening, but is commonly checked for in suspected cases of drug overdose, date rape, and post-mortem toxicology tests. Ketamine (Special K) may or may not be tested for, depending upon the preferences of the entity paying for the test, though testing for it is uncommon. In general, the greater the number of drugs tested for, the higher the price of the test, so many employers stick to the NIDA 5 for financial reasons.

Other drugs, such as meperidine (Demerol), fentanyl, propoxyphene, and methadone are not commonly tested for in most pre-employment situations. These drugs are more likely to be included in tests for certain demographic groups (such as healthcare workers, drug rehab patients, etc.)

Hallucinogens other than cannabis and PCP, such as mushrooms (psilocybin), LSD, and peyote (mescaline) are rarely tested for.

Detection periods

The following chart from LabCorp gives approximate detection periods for each substance by test type. The ranges depend on amount and frequency of use, metabolic rate, body mass, age, overall health, and urine pH. For ease of use, the detection times of metabolites have been incorporated into each parent drug. For example, heroin and cocaine can only be detected for a few hours after use, but their metabolites can be detected for several days in urine. In this type of situation, we will report the (longer) detection times of the metabolites.

• NOTE 1: Oral fluid or saliva testing results for the most part mimic that of blood. The only exception is THC. Oral fluid will likely detect THC from ingestion up to a maximum period of 18-24 hours
• NOTE 2: Urine can not detect current drug use. It takes approximately 6–8 hrs. or more post-consumption for drug to be metabolized and excreted in urine. Similarly, hair requires two weeks, and sweat, seven days.

approximate values for detection periods

Substance	Urine	Hair	Blood
Alcohol	3–5 days via Ethyl Gluconoride(EtG) metabolite or 10–12 hours via traditional method	up to years	12 hours
Amphetamines (except meth)	1 to 2 days	up to 90 days	12 hours
Methamphetamine	2 to 4 days	up to 90 days	24 hours
Barbiturates (except phenobarbital)	2 to 3 days	up to 90 days	1 to 2 days
Phenobarbital	7 to 14 days	up to 90 years	4 to 7 days
Benzodiazepines	Therapeutic use: 3 days. Chronic use (over one year): 4 to 6 weeks	up to 90 days	6 to 48 hours
Cannabis	Single Use: 14 days Chronic Use: Up to 30 days, sometime longer	up to 90 days	2 days
Cocaine	2 to 4 days	up to 90 days	24 hours
Codeine	2 days	up to 90 days	12 hours
Cotinine (a break-down product of nicotine)	2 to 4 days	up to 90 days	2 to 4 days
Morphine	2 days	up to 90 days	6 hours
Heroin	2 days	up to 90 days	6 hours
LSD	2 to 24 hours	Up to 3 days	0 to 3 hours
Methadone	3 days	Up to 30 days	24 hours
PCP	14 days; up to 30 days in chronic users	up to 90 days	24 hours

Common types of drug tests

Urine drug screen

Also known as urinalysis, this procedure requires that one provide a sample of urine. Either a test card is used on site for immediate results (see "General" section), or the sample is sent away to a lab to undergo gas chromatography/mass spectrometry (also known as GCMS), high performance liquid chromatography or immunoassay analysis. The majority of tests administered in pre-hire and even most probate scenarios are of the immediate, and less accurate "at home" variety. Most "dip stick" type tests have higher thresholds for a postive than do the GCMS tests. If a positive result (drug presence indicated) is found, the sample is usually sent to a lab for GCMS confirmation. This is largely due to the costliness of GCMS labaratory testing and time it takes to process and receive results.

The efficacy of urine testing is debatable. It is widely reported that sample substitution and adulteration occur frequently, and both are effective methods of avoiding would be positive tests. There are numerous online retailers of synthetic urine and even prosthetic penises for men to use to excrete this substance under direct supervision. Heat pads are used to keep the substitute sample at a temperature comparable to that of the human body. There are also a number of adulterant "masking" agents that are sold, though they are often nothing more than a simple diuretic and are rarely more effective than caffeine. Some people drink copious amounts of water to successfully dilute the concentration of drug metabolites in their urine below detectable thresholds. Often times this results in clear samples that may be rejected on the grounds of being too dilute, although a complex B vitamin will make urine yellow despite this practice of waterloading. Specific Gravity testing can be done to identify whether or not the sample is of dilute nature, though this is a costly laboratory procedure that is used infrequently on otherwise inconspicuous samples. The substance Niacin is also frequently used for its reported "flushing" effect, though this is also of disputable adeptness. Some types of urinalysis can detect the use of these "detox" product, though they are rarely used unless some facet of the sample is suspicious. Also, the wide availability of at home drug screens allows one to take their own test before they receive one, thus knowing the results ahead of time- giving the user further opportunity to dilute the sample or to find a substitute.

Hair drug testing

Hair testing is quite accurate and can go back normally 3 months (6 months or longer possible with specialty tests), showing any drugs of abuse used in the detection window. As hair grows out, any drugs used are encased in the hair shaft, so the longer the hair, the longer back in the individual's drug history the lab can detect. Accredited hair drug testing labs, however, only use hair within about 2.5–4 cm of the scalp, and discard the rest. With head hair each 0.5 inch (1.27 cm) corresponds to about 30 days. This limits the detection history to about 90 days, depending upon the rate at which the individual's hair grows. Some people attempt to circumvent this through shaving their heads. In the absence of the required amount of hair on the scalp, body hair can be used as an acceptable substitute.

Additionally, for pre-employment hair testing, the inability to obtain a sample may be grounds for not hiring the individual. Hair Testing labs are regulated by CLIA or SAMHSA (not FDA). There is a growing trend in major companies and law enforcement agencies to utilize hair analysis on account of its efficiency and reputation as the gold standard when considering test accuracy. This technology makes use of radioimmunoassay technology with subsequent confirmation by mass spectrometry.

In recent years hair testing has been the subject of a number of law suits. Studies have shown that different ethnic groups have different hair structure leading to false-positives..

Hair alcohol testing

As the hair grows, it absorbs special markers called fatty acid ethyl esters (FAEE’s) and ethyl glucuronide (EtG) into its structure, which remain in the hair indefinitely. These patented markers are only produced when there is alcohol in the bloodstream, and the more markers there are, the more alcohol you drink.

What makes this analysis revolutionary is that it gives a history going back month-by-month or even years if required. No other method can do this. Afterwards, an alcoholic’s treatment can be monitored periodically as their hair grows.

Ethyl glucuronide or EtG is a metabolite only produced when alcohol is in the bloodstream. It is identified as a marker in alcohol hair testing, through a patented analytical process that provides forensic evidence of the pattern of alcohol abuse - or absence of it. The more alcohol a person consumes the greater amount of EtG markers are present in the hair. EtG alcohol testing is unique compared to other alcohol tests in that it allows you to segment testing results into months instead of only days.

The process and test was commercialised for the first time by Trimega Laboratories Limited of London.

Saliva drug screen / Oral fluid-based drug screen

Saliva / oral fluid-based drug tests can generally detect use during the previous few days. Saliva or oral fluid based drug tests are becoming more prevalent because of their convenience and the fact that they can not be adulterated. Furthermore, on-site oral based tests in particular enable the implementation of random testing programs, proven to be the most effective type of drug screening. Oral fluid based tests are as accurate as urine and can be obtained from quality suppliers in the United States. Testing is usually performed by employers, for either pre-employment, random, post-accident, reasonable suspicion, or return-to-duty testing. Oral fluid based testing most closely mimics results found with blood and is preferable for detecting on-the-job drug use or in post-accident applications in this case because the degree of intoxication can be approximated based on the amount of substance

Detection in saliva tests begins immediately upon use:

• marijuana and Hashish (THC): From time of ingestion, up to 24 hours.
• Cocaine (including crack): From time of ingestion up to 2 to 3 days.
• Opiates: From time of ingestion up to 2 to 3 days
• Methamphetamine and Ecstasy (MDMA, "Crank," "Ice"): From time of ingestion up to 2 to 3 days.
• Benzodiazepines: From time of ingestion up to 2 to 3 days.

Sweat drug screen

Sweat tests are patches attached to the skin to collect sweat over a long period of time (10–14 days). These are almost exclusively used by child protective services, parole departments, and other government institutions concerned with drug use over long periods, when urine testing is not practical. The patches have security features that keep them from being covertly removed and then reapplied without the knowledge of the testing agency. At the end of the test period, the patch is removed by a social worker or parole officer and sent to a lab for analysis. If the person has used any drugs during the period that the patch was in place, they will test positive for that drug. This type of testing has fallen out of favor with government agencies due to documented problems with certain drugs.

Drug testing methodologies

The different types of drug tests are tested in very similar ways. Before testing the sample, the tamper-evident seal is checked for integrity. If it appears to have been tampered with or was damaged in transit, the lab rejects the sample and does not test it.

One of the first steps for all drug tests is to make the sample testable. Urine and oral fluid can be used "as is" for some tests, but other tests require the drugs to be extracted from urine beforehand. Strands of hair, patches, and blood must be prepared before testing. Hair is washed in order to eliminate second-hand sources of drugs on the surface of the hair, then the keratin is broken down using enzymes. Blood plasma may need to be separated by centrifuge from blood cells prior to testing. Sweat patches are opened up and the sweat collection component is soaked in a solvent to dissolve any drugs present.

Laboratory-based drug testing is done in a two-tiered fashion using two different types of detection methods. The first is known as the screening test, and this is applied to all samples that go through the lab. The second, known as the confirmation test, is only applied to samples that test positive during the screening test. Screening tests are usually done by immunoassay (EMIT, ELISA, and RIA are the most common). A "dipstick" drug testing method which could at some future time provide screening test capabilities to field investigators has been developed at the University of Illinois. Screening tests are typically less sensitive and more prone to false positives and false negatives than the confirmation test.

Once a suspected positive sample is detected during screening, the sample is flagged and tested using the confirmation test. Samples that are negative on the screening test are discarded and reported as negative. The confirmation test in most labs (and all SAMHSA certified labs) is performed using mass spectrometry, and is extremely precise but also fairly expensive to run. False positive samples from the screening test will be negative on the confirmation test. Samples testing positive during both screening and confirmation tests are reported as positive to the entity that ordered the test. Most labs save positive samples for some period of months or years in the event of a disputed result or lawsuit.

D.O.T. mandated tests require a Medical Review Officer, an M.D. or a D.O., to contact the donor to determine if an alternative medical explanation justifies the presence of the drug identified by the lab. Doctors need not be licensed in the state where the donor resides nor where the test was administered. They must be a licensed physician in one state within the U.S. to participate as an MRO. This substantially limits the degree of influence from out of state medical review boards. In addition, many courts do not allow a private cause of action against MROs, labs, collectors, etc. If an MRO and a D.O.T. participating employer conspire to falsify drug test results, the innocent donor has little if any recourse. The perception that American citizens are "innocent until proven guilty" is just that. Specific mandated drug testing regulations which entitle access to drug testing chain of custody and procedural evidence from the commercial sector may be discounted or ignored by the ODAPC and government agencies. In other words, the government may chose not to enforce their own regulations. To address negligence and abuse, agencies may utilize a PIE (Public Interest Exclusion) to restrict doctors, labs, hospitals and others from participating in D.O.T. testing. Since the implementation of this kind of testing over a decade ago with tens of millions of tests performed, a PIE not has been issued. [needs citation as to accuracy of tests]

Types of testing

Pre-employment drug testing

This is by far the most common type of drug test used by businesses. It has the advantage of being inexpensive, since only one test per employee needs to be paid for by the company. However, since most pre-employment drug testing is urine-based and subject to sample adulteration or substitution, the effectiveness of this approach has been questioned by federal legislators. Some organizations have a witness in the room at the time of the testing, but the privacy implications of this, as well as the potential for shy bladder syndrome has limited the use of witnesses outside jails and drug treatment programs. Companies and testing centers that do not use witnesses normally disconnect sources of water from the testing room to discourage dilution, and if there is water in the toilet, it is dyed blue. Other countermeasures, such as making the donor change into a gown, may also be used.

Random drug testing

This is both the most effective drug deterrence method and the most controversial type of drug testing. Random drug testing is mandated by the U.S. Department of Transportation, which means that many employers in the USA have no choice but to implement random drug testing programs. Even when random drug testing is not legally required, many organizations use small scale random drug testing as an effective deterrence. Random drug testing is not a violation of the Fourth Amendment to the United States Constitution which protects the right of citizens "to be secure in their persons, houses, papers, and effects, against unreasonable searches and seizures." The United States Supreme Court ruled in Skinner v. Railway Labor Assn., 489 U.S. 602 (1989) that random drug testing is permissible for employees in safety sensitive positions. Justice Kennedy, speaking for the majority, wrote:

[T]he Government interest in testing without a showing of individualized suspicion is compelling. Employees subject to the tests discharge duties fraught with such risks of injury to others that even a momentary lapse of attention can have disastrous consequences based on the interest of the general public [...] While no procedure can identify all impaired employees with ease and perfect accuracy, the FRA regulations supply an effective means of deterring employees engaged in safety-sensitive tasks from using controlled substances or alcohol in the first place.

The dissenting opinion by Justices Marshall and Brennan illustrates the other side of the controversy:

The issue in this case is not whether declaring a war on illegal drugs is good public policy. The importance of ridding our society of such drugs is, by now, apparent to all. Rather, the issue here is whether the Government's deployment in that war of a particularly Draconian weapon - the compulsory collection and chemical testing of railroad workers' blood and urine - comports with the Fourth Amendment. Precisely because the need for action against the drug scourge is manifest, the need for vigilance against unconstitutional excess is great. History teaches that grave threats to liberty often come in times of urgency, when constitutional rights seem too extravagant to endure. The World War II relocation-camp cases, Hirabayashi v. United States, 320 U.S. 81 (1943); Korematsu v. United States, 323 U.S. 214 (1944), and the Red scare and McCarthy-era internal subversion cases, Schenck v. United States, 249 U.S. 47 (1919); Dennis v. United States, 341 U.S. 494 (1951), are only the most extreme reminders that when we allow fundamental freedoms to be sacrificed in the name of real or perceived exigency, we invariably come to regret it.

In the United States today, random drug testing is used by a growing number of corporations, drug rehab centers, prisons, the military, police and fire departments, government agencies, and more recently, schools. This method may also be used on teens by their parents, or mandated to be performed on teens at school. The point of a random drug test is deterrence, as the threat of detection is much higher versus other testing methods. Various questionable methods are utilized to determine who gets tested, ranging from drawing names out of a hat, (Government mandated testing requires a scientifically provable method of selection.) to using more defensible methods such as robust random number generators. However, many random drug testing selection systems are legally indefensible because there is nothing to prevent users from targeting individuals by regenerating names with the random generator until the desired result is produced. (Computer generated random selection should have traceable data to validate the legitimacy of the selection.) Most systems have no tamper-proof audit trail (database records are easy to change, so employers or their testing agents must not have access to the audit trail records for the random selection to be defensible). Finally, hiring third parties to randomly select drug testing subjects is not legally defensible because there is no way of proving that there was no collusion to select a specific individual. (I don't believe this is true. A scientifically random selection process is legally defensible.) You are correct that many loopholes plague this system and many people have lost their jobs, reputations, college savings and their homes without as much as an apology from the drug testing giants and the government.

Many apparent conflicts-of-interest exist among service providers and government authorities. In fact, forbidden relationships thrive. The firewalls assuring separation and impartiality don't work. By cultivating relationships forbidden by the regulations the credibility of the entire government sponsored testing program is jeopardized.

While a goal of random drug testing may be to discourage illegal drug use among employees, etc. a goal of so-called "random" testing may be to destroy the career of the tested person, or to prevent the reunification of a family, too. The goals of drug testing vary depending on the motives of those conducting the tests. D.O.T. mandated testing, as codified in CFR 49 parts 40 and 382, define and establish thousands of specific, highly detailed and requisite protocol which must be followed. However, without an effective governing body to monitor, to investigate allegations of non-compliance, and to enforce these regulations, the stated goals of the government are meaningless. Unfortunately, courts throughout the United States are divided on the issue of the right of individuals to bring lawsuits regarding violations of these regulations. In other words, if a laboratory failed to maintain quality controls and your specimen was contaminated at the lab, (this happens) resulting in your termination, many courts deny you and me a legal remedy. Some courts hold that the government created and published strict criteria for laboratories and all other service providers to follow to prevent this kind of failure, thereby giving us substantial "built-in" protection. Through the denial of a private cause of action in these kinds of cases, someone could sabotage your test intentionally with complete impunity. In Drake, after 10 years of legal battles, mostly pro-se, a New York appeals court concluded recently that the language of the 1991 Omnibus Employee Testing Act does not bar common law torts. This is a significant break through for the tested, at-will employee. It is just a beginning, but it is an important legal step in the direction of protecting innocent workers.

Eisenhower warned America of the dangers of a "military industrial complex." The same dynamics have created a collaboration between our government and the commercial drug testing industry.

The goal of random testing is to discourage drug use among employees, inmates, or students by not telling anyone who or when they are to be tested in advance. However, critics claim that random testing introduces a presumption of guilt, and is a violation of privacy if the user is not actually intoxicated during working hours. In addition, random testing is more likely to catch cannabis users, since THC metabolites are fat soluble and have a longer duration in the body than those of many other drugs. Many people believe that this indirectly encourages the use of much more dangerous and harmful drugs that are excreted from the body faster.

Post-incident drug testing

This is not a very commonly administered test compared to the other two, but the financial ramifications of not testing employees after an accident (or other incident) on the job makes this test worthwhile for most businesses. The point of this test isn't necessarily to cause the employee to lose his or her job, but rather to protect the company from liability in the event that the individual is under the influence at the time of the accident. If drugs or alcohol are detected in any significant quantity, the argument can be made in court that the individual was intoxicated on the job, and for that reason, the company should not be held liable for injuries sustained by the employee. This argument, however, can only reasonably be made if blood or oral fluid / saliva testing is used. Urine, hair, or sweat based testing can only detect past drug use. Depending upon the facts of each case, this may help a company avoid litigation completely or may do nothing to help their case. DUI testing would also fall into this category. Another time this type of test may be used is if an employee shows up for work intoxicated, has alcohol on his or her breath, or appears to be impaired in some other way. The goal of these tests is to protect the entity from litigation, so they are only given on an as needed basis.

It should be noted that in most areas, blood testing is the only legally defensible means for detecting drug use after an incident, although saliva testing is gaining acceptance. The sample should follow chain of custody requirements and should always be sent to a lab after collection. Positive on-site tests that may affect an employee's position or situation should always be followed up with a laboratory test before any action is taken against the employee. Laboratory tests (urine or blood) are the only legally recognized tests in most states as well as in most non-U.S. countries.

Pros and Cons of Drug Testing Methods

There is no perfect drug testing method. Each method has some advantages and disadvantages. What makes a drug testing method good or not so good is more related to the needs of the person.

Urine Drug Testing

Pros: Urine drug test kits are available as on-site tests, or laboratory analysis. Referred to as "the gold standard", urinalysis is the most common test type and used by federally mandated drug testing programs.

Cons: The main disadvantages of urine-based drug test kits is are (1.) the ease at which they can be "cheated" via sample adulteration or substitution, unless specimen collection is directly observed, (2.) inability to detect current / on-the-job drug abuse, (3.) the need for bathroom facilities, and (4.) with respect to SAMHSA-5, or NIDA-5, the inability to test for drugs used in current society.

Saliva Drug Testing

Pros: Saliva (Oral) drug test kits are very donor friendly, non-invasive and easy to collect the specimen. There is no need for a bathroom to administer the tests. Saliva drug testing is great at detecting very recent drug use. Also these drug tests are harder to adulterate than the urine drug tests since the sample can be obtained under direct supervision. Results can be read in minutes and there is no need for a lab. Depending on the test, up to 8 (5 or 6 at a time) different drugs could be detected. This method is the best method for determining current use and impairment.

Cons: The main disadvantage of saliva based drug testing is lack of awareness in the market, as well as misinformation spread largely by laboratories and TPAs (third party administrators), who stand to lose money as saliva testing continues to replace traditional urine-based techniques.

Spray (Sweat) Drug Testing

Pros: Spray (Sweat) drug test kits are non-invasive and donor friendly. It is very easy to collect the specimen and no bathroom is needed for taking the specimen. The detection window is long and usually can detect drug use up to a couple of weeks. These drug tests are relatively tamper proof since they are hard to manipulate. There is no need for a lab and you can get results in minutes.

Cons: The main disadvantage of spray or sweat based drug testing is the fact that they are open to contamination. Also large variations of sweat production rates of possible donors make some results inconclusive. There is not much variety in these drug tests since they are not as popular as urine or saliva drug testing kits. Their prices tend to be a little higher per test conducted. One main disadvantage of this testing method is the limited number of drugs that can be detected.

Hair Drug Testing

Pros: Hair Alcohol Testing can provide a much longer window of detection.

Cons: Costs more than urine testing. Cannot be used if a donor has no hair.

Legality and ethics of mandatory drugs testing

United Kingdom

The legal position of drug tests on the UK is not clear. A recent study by the independent Inquiry into Drug Testing at Work found that attempts by employers to force could be challenged as a violation of privacy under the Human Rights Act 1998 and Article 8 of the European Convention of Human Rights. However, this may not extend to industries where drug testing is a matter of safety rather than productivity.

See also

• Urinalysis
• School district drug policies

External links

• HealthWorks-WNY Drug and Alcohol Screening Services
• US National Institute on Drug Abuse (NIDA) Website
• US Substance Abuse and Mental Health Services Administration (SAMHSA) Website
• Oral fluid test developer
• Erowid Drug Testing Vaults: The Basics
• Marijuana Detection Time Shorter Than Previously Assumed
• What You Need to Know about Drug Testing Methods
• Daily news about drug testing
• A Political History of White House Drug Policy
• Ronald Reagan's Executive Order 12564
• The (US) National Clearinghouse for Alcohol and Drug Information
• The (US) National Institute on Alcohol Abuse and Alcoholism
• European Workplace Drug Testing Society
• The Drug and Alcohol Testing Industry Association