In this module, we'll be reviewing MRO work in reviewing positive results. If a donor tests positive, the burden of proof is on the donor to provide what is called an alternative medical explanation. That means they have to provide a legitimate explanation, such as a prescription or evidence of use of a drug during a medical encounter. The only exception is for opiates below the level of 15,000 nanograms because they could be caused by the use of poppy seeds. The donor is usually given five days to provide documentation, which would either come from a pharmacist or from a prescribing physician. The regulations don't specify whether that's five calendar or business days, but I generally allow a little leeway for the donors. So if the donor can provide a prescription or a legitimate explanation, then that will be reported as a negative. Now this is a key point for new MROs. If a confirmed laboratory positive comes to an MRO, the MRO can report it as a verified negative. Not because it's a negative test in terms of the laboratory result, but it's negative because the person did not have unauthorized use. And that's a key point that every MRO has to get under their belt. Again, with a positive, you're also going to raise your ears and say, is there a potential safety consideration at the workplace? Given the ease of forgery of prescriptions, it's important that the MRO verify the prescription. And that means having a contact directly with the pharmacist or with a treating physician's office. I usually put the burden of proof on the donor and say, you have five days to contact your doctor or pharmacist. You can sign whatever release forms are needed. But I need to have faxed to my number a medical verification. Given the ease of forgery, now people are being asked to do double verification, which means maybe the donor will send you a photograph of a prescription bottle. But even though you have that, you may want to call the pharmacy and verify that it came from that pharmacy. Most important is that you cannot simply state or check a form on the CCF that says it is a negative. You have to have written documentation of your rationale and the evidence that you used. So we cannot say often enough, document exactly what you do, use the MRO checklist, and write down all the steps that you are following. So far, I have spoken of authorized medical use. But sometimes an MRO is asked to go further and decide whether there is appropriate medical use. The best example of this would be with the Department of Health and Human Services in their MRO manual, which guides the evaluation of federal employees. And there, the language, as you see here, is quite specific. Was the prescription generated in response to the donor's current medical condition? And was it used during the time period for which it was legitimately prescribed? So those are very high standards. But there is no specific guidance about the age of prescriptions. And that does not come from the Drug Enforcement Administration either. One of our faculty members, Dr. Wes Clark, is also an attorney. And he's made it very clear that in his opinion, if a prescription was written for a particular individual, for a particular drug, and it was given on a PRN basis, it doesn't make any difference how old the prescription is. MROs need to be physicians because there's a fair amount of discretion and clinical judgment that is needed. And here are some problem situations. First is if a drug was obtained legally in a foreign country. So somebody was traveling to a country where they were prescribed, let's say, amphetamines, and there was a legitimate reason for it at the time, and it was used consistently. In that case, an MRO would probably verify it as being a negative. However, if the person decided that they really liked that drug, and they kept getting those little brown pills sent from Mexico, then at that point, it is really not authorized use. Another example would be somebody who is using hashish or marijuana, let's say, in Amsterdam, where it is legal. However, it's not medically authorized. And if a person flies back, they have a test, and they test positive for marijuana, that would not be considered an authorized use. One gray area that was debated for many years was the use of a friend or a family medication, sometimes called spousal or friendal use. The federal regulations are unclear about that, but obviously, the medication of someone else was not authorized for that person. But I have gone as far as saying, if you can get your spouse's doctor to write me a note and say that you were authorized to use their medication, I will report that as a negative. That doesn't happen very often. We talked earlier about the time of medications, and the question comes up, what if a medicine was prescribed more than six months ago or a year ago? Again, the DEA is silent on this, and this is a matter of MRO discretion. One of the most heartbreaking situations was people who received a medication over the internet, and then when they went to verify it, there was no doctor to verify the questionnaire that they had filled out and the telephone interview they'd had. But fortunately, the Ryan Hate Act in 2009 has now made it illegal to dispense controlled substances by way of the internet. So how often do MROs reverse laboratory positives and report them as negatives? Well, this is quite old data, but it shows a very definite trend and gives you a sense of how frequently. In 2006, for federally regulated test panels, about 10% of the time, a test was reported as a negative, and by 2009, that had gone up to 24%, so almost one in four. For non-federally regulated drug panels, which would include drugs such as benzodiazepines, you can say that during the same period, it went from about a quarter of the cases up to 43%. So the take-home is that it's not unusual for an MRO to reverse a laboratory positive. The real question is, what was the specific drug for? So here you have your answer. In the case of fencyclidine, on the bottom row, you see that none of the laboratory positives were reported as verified negatives. In the case of cocaine, 99.9% of the laboratory positives were verified as positive, and similarly for marijuana, 99.5% of the time, they were verified as positives. That's about one out of 200 cases. However, when you look up above at the semi-synthetic opioids, you see that in two-thirds of the cases, oxymorphone was reported as a verified negative, so there was a legitimate prescription for that. And in the case of hydrocodone, it went up as far as 85%. Let's go through the five classes of drugs, starting with the easy ones for the MRO. So you see that for PCP and MDMA, there is never a medical explanation, never a legitimate use. So why communicate with the donor? Well, obviously, as MROs, we are required to offer an interview to donors of non-negative results, and that includes these drugs. But remember, we're also offering the first opportunity to talk with the person about their drug use, and that may sensitize them to the fact that they have a drug problem and that they really ought to get some medical help. In the case of cocaine, we know that there are many legitimate explanations for ENT and bronchoscopy, for example, or to shrink the nasal mucosa to be able to visualize the sinuses. Departments use cocaine to shrink blood vessels and receive a better view of the eye. And emergency departments used to use a liquid called TAC, tetrakane, adrenaline, and cocaine, as a way of shrinking blood vessels and therefore allowing the debriding of abrasions and rough wounds. But very seldom are you going to be reversing a cocaine positive. In the case of marijuana, quite the opposite is true. Most of the time, a marijuana positive will be reported as marijuana. So let's be clear. The only acceptable explanation for tetrahydrocannabinol is an authorized prescription of Marinol or one of the other Schedule III drugs. Under federal regulations, otherwise, you would always call this a positive. Now in the non-federally regulated situation, then it depends on the company policy. And you're working as an agency for the company, so you need to know their policy. And it also depends on state laws, which can be quite detailed. We do know, though, that the use of marijuana and the THC definitely increases the risk of motor vehicle crashes. This has certainly been shown in the states where recreational marijuana is permitted. And for that reason, commercial motor vehicle drivers are not allowed to use medically recommended marijuana. Now that medical marijuana is authorized in a majority of states, the question repeatedly comes up, is medical marijuana an acceptable medical explanation? And I've just told you that under the federal regulations, which always supersede state regulations, a Schedule I drug is not considered an acceptable explanation. So there's no question of debate there. But in the non-federally regulated drug testing, there are a lot of different opinions. The Medical Review Officer Certification Council and its counterpart, the American Association of Medical Review Officers, says an MRO is an agent of the employer, and so their actions should be guided by the employer's policy. I think that makes a lot of sense. ACOM and the American Academy of Occupational Health Nurses collaborated in a report, and they said the MRO should report these as positive, and then provide an explanation that there was a medical marijuana recommendation. So basically, put the monkey onto the employer's back and let them make the determination, since they know the nature of the work and the safety hazards. At one time, the ACOM MRO section, that is a group of MROs within ACOM, actually said, well, the MRO could determine whether the medical facts corroborate valid medical marijuana use. But here, I think you're going beyond being an MRO, and you're getting into clinical medicine and clinical judgment. And I think it's very problematic, during a very brief telephone interview, to be able to have enough discernment to make a good call on that. The Federation of State Medical Boards, which governs the licensing of physicians in different states, has looked long and hard at the issue of medical marijuana. And they have published what they call a set of expectations for physicians who are recommending marijuana. They're not absolute rules, they're expectations. And remember, physicians cannot prescribe marijuana. They can only recommend it, in which case a person can take that recommendation and go and get a marijuana card, and then receive marijuana at a legal dispensary. So FSMB has recommended that a physician first look at a variety of alternative measures to ease symptoms, and not use marijuana as sort of the first drug of choice. They also detailed 10 expectations of physicians involving marijuana in medical care. And they involve having a doctor-patient relationship, having a formal medical record, doing an appropriate history and physical examination. There needs to be a treatment agreement, so that the patient understands the consequences of the treatment. And also, there needs to be ongoing monitoring. They also have, as one of their strong points, that physicians recommending marijuana should personally abstain from marijuana, either medically recommended for them, or for recreational purposes. The last thing I'm going to say about marijuana is that there is a test called THCV, a test for tetrahydrocannabivarin, which is performed at a few laboratories, and might be used in discerning the use of marijuana versus prescription Marinol. THCV is a metabolite produced by the burning of THC. So it's not going to be found in the prescribed medication. So it often can be used to differentiate whether a person actually smoked marijuana, or did they take a pill of dronabinol. If THCV is present, it's consistent with the smoking, but it's not always present. So if you have a negative THCV, that doesn't mean that you were not smoking. The problems are that it's an additional cost. It's only done at two laboratories. And if you're going to use it, I would say you should be discussing this with the employer, and they should have good reasons to want to pursue this further. So this is the end of our discussion of marijuana. Now let's move on. The second drug class in the federal panel are the amphetamines. And here you see amphetamine and methamphetamine. So I know Dr. Pete has gone through this in detail, but I want to say as an MRO, I try to simplify the complex. So in my simple brain, I think of methamphetamine as amphetamine that's had a methyl group added to it. So in the metabolism of methamphetamine, the methamphetamine is lopped off, and it becomes amphetamine. And that's why there always needs to be the presence of a certain amount of measurable amphetamine in order to confirm that it is a valid laboratory positive for methamphetamine. Dealing with a confirmed positive methamphetamine is not as difficult as it might initially appear. What is important is the D and L isomers of methamphetamine. So I know Dr. Pete spoke about them as the dextro, or right-handed rotation, and the levo, or left-handed rotation of the isomers. But again, as an MRO, I tend to simplify the complex. So I think of the D isomer as representing the use of a drug and an L isomer as representing a legal prescription medication. You'll need to remember that 100 nanograms per ml of amphetamine has to be present for a laboratory to report a positive methamphetamine to you. We know that the cutoff level for amphetamine is 250 nanograms per milliliter and therefore, if it's less than 250, the lab will report it as a positive methamphetamine, but a negative amphetamine. And it's important for an employer to follow Dr. Peet's recommendation and have a routine characterization of D and L isomers whenever the laboratory has a positive methamphetamine. Otherwise, it's going to be much more costly to do the DL separation. It's going to slow things down and so it's important to know what the protocol is with a particular employer and laboratory. So in your interview with a donor, you're going to want to explore the use of prescription medication or over-the-counter medication that might contain D methamphetamine. You'll probably want to ask about the use of nasal inhalers. Dr. Peet has indicated that the current formulation of Vicks inhaler does not include methamphetamine, but the older forms do, and they're going to be sitting on people's medicine cabinets or drugstore shelves for quite a long time. And you need to, again, know your prescription drugs. For example, selegiline, which is used in the treatment of Parkinson's disease, definitely will test positive for methamphetamine. So this is why the characterization of D and L is so important. Laboratory analysis of people taking Vicks inhaler will show a large percentage of L or legal methamphetamine and little or no D or drug methamphetamine. And there's what's called the 80-20 rule, which is very, very helpful here. There is some cross-reactivity between the L and the D form of methamphetamine, but if there is at least 80% of L methamphetamine, then I will verify that as a negative. However, if it exceeds 20% of the D form, then I'm going to assume that the person was using D methamphetamine, a drug form, and they tried to mask it then by taking Vicks inhaler to try to cover it up. Notice that selegiline will give you equal amounts of amphetamine and methamphetamine, but those are both in the L or legal form. So here's an important study tip for you, and that is to know the prescription medications that can cause a confirmed positive test. And there's two lists that you should find useful to study as an MRO and also to study for the MROC exam. The first is in Dr. Peet's tab, and it was a list prepared by officials at SAMHSA of drugs that could cause a positive test. The second one is at the back of this tab, and it's a table from Robert Switinsky's MRO manual, and it goes through each class of drug and shows which ones can cause a positive result. So this is where I would concentrate my effort if I were studying for an examination. Now we've dealt with amphetamines. The situation becomes a little more complicated with opioids, and that's where we'll head next. The classical opiates include these three drugs on the federal panel. After we've reviewed them, then we will look at the semi-synthetic opioids. For a donor with a positive 6-acetyl or 6-monoacetylmorphine analysis, there will be no discussion about alternative medical explanations. This is considered to be pathognomonic of using heroin, so you will verify this as a positive after talking with a donor. However, for the other two opiate drugs, things are a little more complex, there's a 15,000 level cutoff, which represents the threshold between possible use of poppy seeds and prescription medications. So if the level is at or above 15,000 nanograms, then, as with the other drugs, the donor has the burden of proof of providing you with a documented medical explanation. However, if the morphine or the opiate However, if the morphine or codeine is between 2,000 and 15,000, then you will call this a negative unless there is some what is called independent clinical evidence of unauthorized opiate use. You can tell that was written by attorneys. So what is clinical evidence? Well, clinical evidence could include something that you learned in the examination or the interview. We all know that the medical history is probably the most important and the most underrated aspect of clinical care. So if a person tells you that they were using an opiate, if they were using someone else's medication, then that is considered clinical evidence. Otherwise, you'll need to look for physical exam signs of needle tracks or abnormal behavior, signs of acute intoxication or withdrawal, et cetera. And that will probably not stand up in court if the documentation was done by a non-medical profession specimen collector, but if a nurse or a physician observed that behavior, then you're on stronger ground. Now, the federal regulations are silent on what can be called spousal use or friendly use. Here's a situation where somebody, let's say, was traveling. They had a severe headache. They were with a wife or a friend. They took their opiate medication to relieve the pain. And then after being tested, it was positive. I think I mentioned that in this case, it's a matter of your clinical judgment as an MRO, but I have gone so far as to tell an individual that if they could get their own doctor to write a note saying that they authorized you to use this as a spouse or a friend, then I will consider that a legitimate explanation. In talking to people, it's also important to realize that people may tell you that they were using other medication, like oxycodone or hydrocodone, to explain an opiate positive. And that is not gonna be an adequate explanation for those laboratory values, but it will, again, raise the question of workplace safety. Here's a slide that summarizes the reporting of opiate results. You can report a verified positive if you are unable to contact the donor through either the three or the 10-day clock. You can report a positive for a donor who refuses to speak with you. You will automatically report a positive for a 6-acetylmorphine. You'll report a positive for a opiate at or above 15,000 nanograms, and there was no documentation of authorized use. And finally, in rare situations, you would report a positive if there were independent clinical evidence of unauthorized use. Otherwise, you would call a negative opiates that are at or above 15,000, and there was a documented prescription or medical procedure that explained the result, and for opiates between 2,000 and 15,000 where there was no independent clinical evidence. So if somebody says, doc, I don't know what a poppy seed looks like. I have no idea why this is negative. You are going to call this a negative. Turning to the semisynthetic opioids, you see that these four specific drugs were added to the federal panels in 2017 and January of 2018, and you should know their screening and their confirmation levels. This means that MROs are going to need to become familiar with the brand names of many of the different opioids. So here you see a number of them containing hydrocodone, and I've bolded Vicodin. The same is true with hydromorphone. Some of the most commonly used oxycodone products are Percocet, Percodan, and OxyContin. So Dr. Peet showed a complex metabolic pathway for various opiates and opioids, but again, as an MRO, I try to simplify things. So in my mind, what's important to remember is that the codones are metabolized to the morphones. So hydrocodone becomes hydromorphone, oxycodone becomes oxymorphone, and this has important implications, which we'll cover. Frequently, the parent compounds disappear more quickly than their metabolites. So a person who's taking oxycodone and has a prescription for that could test positive only for oxymorphone. And the same is true with hydrocodone, which could only test positive for hydromorphone. At some point, people were trying to rely on parent metabolite ratios, but because they change throughout the metabolic cycle, that is not something that MROs can use for guidance. Let's apply what we just learned in three actual real-world case studies. We had a case where a laboratory reported a morphone at 11,000 nanograms and a methamphetamine at 3,000 nanograms and an amphetamine at 500. So it was positive for three different substances. Interestingly, the donor admits to taking suboxone, which is a treatment for people who have been addicted, but he totally denied taking amphetamines. He also said he was taking a large number of nutritional supplements, and he texted me photographs of those that had been recommended by the doctor. So think for a moment. What are the actions that you should take? In this case, the two things that I did were to order a DL separation for methamphetamine. We've covered that that is recommended as a routine measure. And in terms of the supplements, I had the benefit of being able to talk with Dr. Pete about the nutritional supplements. So three results came back. First of all, Dr. Pete confirmed that none of the ingredients in the nutritional supplements could explain the laboratory findings. Secondly, the laboratory did report 88% of the methamphetamine in the D isomer. So that exceeded the 80-20 rule. And therefore, I would say that that's highly likely that he's taking a drug and not a medication. And finally, the donor did want a split specimen sent to a different lab. So what should you do now? Do you wait for the split specimen results? That's a mistake I only made once in my career. But once you have a confirmed and verified positive, you can go ahead and report that before you get the split sample results. Do you call it positive for methamphetamine or do you call it positive for methamphetamine and amphetamine? And there you need to remember what the cutoff levels were. The amphetamine was 500 and it had to be at least 250 to be reported. So I would call that a positive for both methamphetamine and amphetamine. I would definitely not call it a negative even though there would be safety concerns. And I would not cancel the test. Our second case study is positive for amphetamine. And in speaking with the donor, he was full of information. He said he was eating poppy seed bagels, he'd been drinking health Inca tea, and he had a prescription for Ritalin that he could document and he was also taking Cipro for diverticulitis. He did want the split to be analyzed. So what does the MRO report? Well, in this case you can see that donors can often give you lots of reasons why a drug test might be positive. But of course the poppy seed bagels would be for morphine, the health Inca tea would be for cocaine, Ritalin does not cause a positive amphetamine and that's something important to remember. And Cipro for diverticulitis deals with people who sometimes have a reported invalid result. So these are the kinds of red herrings that you will hear when you talk with people as an MRO. So do you wait until the split result was received? Well, we just said in the last case, you do not wait once you have your verified result. It's definitely not a negative and therefore not a negative with safety concerns, you're not gonna cancel it. So this is a positive case for amphetamine. If the donor had had a valid prescription, which of the following medications could explain a positive amphetamine? And here's where I said earlier, you need to really know your medications and which ones can cause positive drug test results. So I'm not gonna answer this for you, but I'm gonna suggest that you look it up and know this information. Our final case study deals with the semisynthetic opioids. So here's a donor who tested positive for hydromorphone at 225 nanograms per milliliter and his hydrocodone was negative, but he denied use of morphine or hydromorphone and he did present a valid prescription for hydrocodone. So here's the question, what are the possible reasons why the hydrocodone was negative? Was it A, because it was present, but below the cutoff? Well, that certainly could have been true. Or B, was the hydrocodone metabolized more quickly than the metabolite? I've already said that that frequently happens. So that also could be true. And third, perhaps he took Dilaudid, but he submitted a hydrocodone prescription. That also would be a true answer. So all of those would be possible explanations. So in this case, what do you report to your employer? Is it positive for opioids? Is it positive for hydromorphone? Is it a negative or is it an invalid? And the correct answer is it's a negative because the prescription for hydrocodone could explain the presence of hydromorphone. So that resolves the classic MRO decision. Now, the next question that arises is, would this cause you to have concern about a workplace safety issue? And we're gonna be talking about that more in the fourth module in this segment. In closing this module on the reporting of positives and legitimate medical explanations, I just wanna point out two additional resources. The first is the list that I spoke about earlier of medications sold in the U.S. that can cause confirmed positive results. And this includes both over-the-counter medications as well as prescription drugs. It comes from Robert Swietynski's Medical Review Officer's Manual and it's Exhibit 11.3, which we have reprinted with permission. The second is the expectations and guidelines for physicians recommending marijuana in patient care. I mentioned that earlier and these are both included in your syllabus.

Medical Review Officer

drug test results

positive results

legitimate medical explanation

alternative medical explanation

opiates

documentation