Saturday, September 11, 2010

Another UDT Study Distorts Opioid Noncompliance

UDTA newly-reported investigation found via urine drug testing (UDT) that up to a third of patients are noncompliant with prescribed opioid regimens. However, rather than elucidating the causes of noncompliance or supporting the value of UDT, the validity of this sort of “pseudo-research” needs to be questioned.

Despite some limitations regarding the clinical utility and validity of UDT [previously noted here and here], it remains an important tool for many practitioners in assessing whether patients are compliant with prescribed opioid therapy regimens. Writing in the July/August 2010 edition of the Journal of Opioid Management (JOM) investigators describe a retrospective comparison of analgesics prescribed for chronic pain and corresponding UDT findings [West et al. 2010]. Data were derived from UDT results of 20,457 patients recorded during an unspecified time period. Noncompliance was defined as absence of the parent drug and/or metabolite determined by high-sensitivity liquid chromatography-mass spectrometry (LC-MS/MS) assays that allowed for very low drug-detection cutoff levels.

Reported noncompliance rates for various analgesics were: methadone 9%, morphine 14%, oxycodone 23%, hydrocodone 24%, and carisoprodol 33% (muscle relaxant/analgesic). The authors conclude that noncompliance was prevalent in this extensive patient population and varied with the prescribed drug; however, there are a number of profound limitations and biases of this research that must be considered.

COMMENTARY: First, all 8 coauthors of this report were employees of Millennium Laboratories, a commercial UDT facility in San Diego, CA. Claiming high rates of noncompliance, as revealed only by UDT, is good for generating further business; so, this article seems like more of an infomercial than genuine research. Frankly, we were surprised that the editors of JOM — which usually features substantive and less biased articles — would even consider this paper for publication.

Second, this study is unhelpful for understanding the true extent or basis of noncompliance. The greatest concern would be that absence of a prescribed drug in urine denotes diversion for illicit purposes. However, the authors did not have information on the prescribed dosing regimens and concede that many of the drugs might have been for occasional breakthrough pain or only short term use. Plus, the timing of urine sample collection following the last dose of the drug in question could have made a difference (eg, in cases of rapid drug metabolism). Therefore, many (or most?) drug-negative UDT results could have been in completely compliant patients.

Third, in many cases, as has been found in other research, patients may not be regularly taking their analgesics due to cost concerns; in a sense they are being noncompliant with the prescribed regimen but their motives are economic; not mischievous. It is interesting in this regard that methadone, the least expensive analgesic tested, had the lowest rate of noncompliance. The authors cite other recent research that found up to 22% of patients do not even fill their medication prescriptions. In sum, this research overall tells us nothing of truly practical clinical value, other than the sponsoring laboratory was very good at detecting the presence or absence of the drug(s) in question.

This is not the first time we have observed spurious and biased research concerning UDT for therapeutic monitoring of analgesic compliance. About a year ago, we reported [here] on a study claiming three-quarters of patients prescribed opioids for chronic pain were noncompliant. It was presumed that the absence of pain medications, in 39% of all samples, indicated substantial drug diversion. In another 27% of patients classified as “noncompliant” opioid levels were actually higher than expected. This particular research was sponsored by Ameritox, another UDT laboratory, and the authors claimed that their study confirmed “the importance of periodic drug screening for the population prescribed long-term opioid therapy” — which might be interpreted as a rather self-serving conclusion.

In our opinion, so-called “research” reports of large-scale opioid noncompliance are scare tactics; not clinically valid or helpful evidence. Noncompliance can have several meanings and different etiologies; most of which do not signify misbehavior or drug diversion. In select cases, prescribers may indeed find UDT helpful for confirming an unexpected absence of drug in the patient’s system. However, it takes a skillful and caring healthcare provider to consult with the patient in discerning the underlying causes of this and arriving at appropriate therapeutic solutions.

REFERENCE: West R, Pesce A, West C, et al. Observations of medication compliance by measurement of urinary drug concentrations in a pain management population. J Opioid Management. 2010(Jul/Aug);6(4):253-257 [journal TOC here].