The Association Between State-Level Prenatal Substance Use Policies and Rates of Maternal Mortality in the United States: A Legal Epidemiology Study.

Little research has explored relationships between prenatal substance use policies and rates of maternal mortality across all 50 states, despite evidence that prenatal substance use elevates risk of maternal death. This study, utilizing publicly available data, revealed that state-level mandated testing laws predicted maternal mortality after controlling for population characteristics.

Structural Racism in Newborn Drug Testing: Perspectives of Health Care and Child Protective Services Professionals.

PURPOSE: Black birthing parents and their newborns disproportionately experience newborn drug testing for prenatal substance exposure by health care professionals (HCPs), which contributes to Child Protective Services (CPS) reporting, family separation, and termination of parental rights. This qualitative study aims to interrogate dominant power structures by exploring knowledge, attitudes, and experiences of HCPs and CPS professionals regarding the influence of structural racism on inequities in newborn drug testing practices. METHODS: We conducted semistructured interviews with 30 physicians, midwives, nurses, social workers, and CPS professionals guided by an explanatory framework, and conducted inductive, reflexive thematic analysis. RESULTS: We identified 3 primary themes: (1) levels of racism beyond the hospital structure contributed to higher rates of drug testing for Black newborns; (2) inconsistent hospital policies led to racialized application of state law and downstream CPS reporting; and (3) health care professionals knowledge of the benefits and disproportionate harms of CPS reporting on Black families influenced their decision making. CONCLUSION: Health care professionals recognized structural racism as a driver of disproportionate newborn drug testing. Lack of knowledge and skill limitations of HCPs were barriers to dismantling power structures, thus impeding systems-level change. Institutional changes should shift focus from biologic testing and reporting to supporting the mutual needs of birthing parent and child through family-centered substance use treatment. State and federal policy changes are needed to ensure health equity for Black families and eliminate reporting to CPS for prenatal substance exposure when no concern for child abuse and neglect exists.

Cannabinoids detected in exhaled breath condensate after cannabis use.

Cannabinoids can be detected in breath after cannabis use, but different breath matrices need to be explored as studies to date with filter-based devices that collect breath aerosols have not demonstrated that breath-based measurements can reliably identify recent cannabis use. Exhaled breath condensate (EBC) is an unexplored aqueous breath matrix that contains condensed volatile compounds and water vapor in addition to aerosols. EBC was collected from participants both before and at two time points (0.7 ± 0.2 h and 1.7 ± 0.3 h) after observed cannabis use. Eleven different cannabinoids were monitored with liquid chromatography tandem mass spectrometry. Five different cannabinoids, including Δ9-tetrahydrocannabinol (THC), were detected in EBC collected from cannabis users. THC was detected in some EBC samples before cannabis use, despite the requested abstinence period. THC was detected in all EBC samples collected at 0.7 h post use and decreased for all participants at 1.7 h. Non-THC cannabinoids were only detected after cannabis use. THC concentrations in EBC samples collected at 0.7 h showed no trend with sample metrics like mass or number of breaths. EBC sampling devices deserve further investigation with respect to modes of cannabis use (e.g, edibles), post use time points, and optimization of cannabinoid recovery.

Challenges encountered in the enantioselective analysis of new psychoactive substances exemplified by clephedrone (4-CMC).

In this study we report on efforts to develop an enantioselective method for the detection of the drug of abuse clephedrone (1-(4-chlorophenyl)-2-(methylamino)-1-propanone (4-chloromethcathinone, also known as 4-CMC or para-chloro-methcathinone)) and its phase-1 metabolites in human biological fluids. The major goal is not to only report results, but primarily to emphasize the various challenges encountered when developing a reliable analytical method for the detection and quantification of novel psychoactive substances (NPS) and their metabolites in the matrix of interest. Such challenges start with the lack of chemical stability of some NPS in biological matrices. Additionally, most often metabolites are unavailable in pure form to serve as analytical standards, just as deuterated standards for native drugs and metabolites are frequently not commercially available. Furthermore, if the NPS is chiral, enantiomerically pure standards with known absolute stereochemistry are required, as well as a stereochemical stability of a drug and its metabolites becomes an issue. In addition, the chirality of a NPS significantly increases the number of species to be detected in the sample and thus challenges the development of an adequate separation method. These issues are shortly addressed, and some solutions offered in this manuscript.

Drugs in blood and urine samples from victims of suspected exposure to drink spiking: A prospective observational study from Oslo, Norway.

OBJECTIVE: People regularly contact emergency medicine services concerned that they have been exposed to drink spiking, i.e., exposure to drugs without their knowledge or permission. We identified drugs in blood and urine samples from patients suspecting exposure to drink spiking, with special consideration for drugs not reported taken by the patient (unreported drugs). METHODS: From September 2018 to May 2019, we collected blood and urine samples from patients 16 years or older presenting at an emergency clinic in Oslo, Norway, within 48 hours of suspected exposure to drink spiking. We also collected information on ethanol ingestion and drugs taken. Blood samples were analyzed for 20 classical recreational drugs using ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) and an automated enzymatic method for ethanol. Urine samples were analyzed using immunoassay methods and a specific gas chromatography mass spectrometry (GCMS) method for gammahydroxybutyrate (GHB). RESULTS: From 100 included patients (median age 24 years, 62 females), we collected 100 blood samples and 72 urine samples. Median time since exposure was 5 hours. Unreported drugs were found in 15 patients. Unreported drugs in the blood samples were clonazepam in 3, methylenedioxymethamphetamine (MDMA) in 3, amphetamine in 2, tetrahydrocannabinol (THC) in 2, tramadol in 1, cocaine in 1, and methamphetamine in 1. Unreported drugs in the urine samples were cocaine in 5, amphetamine in 4, ecstasy in 3, and cannabis in 2. Ethanol was found in 69 patients, all reporting ethanol ingestion. Median blood ethanol concentration was higher in patients with no unreported drugs detected, 1.00‰ (interquartile range (IQR) 0-1.52) vs. 0‰ (IQR 0-0.46) (p<0.001). GHB was not detected. CONCLUSION: Unreported drugs, possibly used for drink spiking, were found in 15% of patients. Blood ethanol concentration was higher when no unreported drugs were found. GHB was not detected in any patient.

Psychometric properties of the modified Drug Abuse Screening Test Sinhala version (DAST-SL): evaluation of reliability and validity in Sri Lanka.

BACKGROUND: Psychoactive drug use is an important public health issue in Sri Lanka as it causes substantial health, social and economic burden to the country. Screening for substance use disorders in people who use drugs is vital in preventive health care, as it can help to identify problematic use early. Screening can aid in referring those in need, for the most appropriate treatment and care. Thus, preventing them from developing severe substance use disorders with complications. The Drug Abuse Screening Test (DAST-10) is an evidence-based tool widely used to assess the severity of psychoactive drug use. This study aimed to culturally adapt and evaluate the validity and reliability of the Drug Abuse Screening Test (DAST-10) in Sri Lanka. METHODS: The DAST-10 was culturally adapted, and the nine-item Sinhala version (DAST-SL) was validated using exploratory and confirmatory factor analysis. The validation study was conducted in the Kandy district among people who use drugs, recruited using respondent-driven sampling. Criterion validity of the questionnaire was assessed by taking the diagnosis by a psychiatrist as the gold standard. Cut-off values for the modified questionnaire were developed by constructing Receiver Operating Characteristic (ROC) curves. The reliability of the DAST-SL was assessed by measuring its internal consistency and test re-test reliability. RESULTS: The validated DAST-SL demonstrated a one-factor model. A cut-off value of ≥ 2 demonstrated the presence of substance use disorder and had a sensitivity of 98.7%, specificity of 91.7%, a positive predictive value of 98.8% and a negative predictive value of 91.3%. The area under the curve of the ROC curve was 0.98. A cut-off score of ≤ 1 was considered a low level of problems associated with drug use. The DAST-SL score of 2-3 demonstrated a moderate level of problem severity, a score of 4-6 demonstrated a substantial level of problems, and a score of ≥ 7 demonstrated a severe level of drug-related problems. The questionnaire demonstrated high reliability with an internal consistency of 0.80 determined by Kuder-Richardson Formula-20 and an inter-class correlation coefficient of 0.97 for test re-test reliability. CONCLUSION: The DAST-SL questionnaire is a valid and reliable tool to screen for drug use problem severity in people who use drugs in Sri Lanka.

Observations on the effects of buprenorphine and methadone on illicit drug use.

OBJECTIVE: To determine if the agonistic effects of buprenorphine and methadone affect drug use. METHOD: Quantitative examination of urine drug concentrations of patients treated with buprenorphine and methadone. RESULTS: Patients on buprenorphine had less opioid and methamphetamine drug use than those on methadone. CONCLUSION: Patients on buprenorphine therapy appear to use less illicit drugs.

An urgent need for community lot testing of lateral flow fentanyl test strips marketed for harm reduction in Northern America.

BACKGROUND: Fentanyl test strips (FTS) are lateral flow immunoassay strips designed for detection of ng/mL levels of fentanyl in urine. In 2021, the US Centers for Disease Control and the Substance Abuse and Mental Health Administration stated that federal funds could be used for procurement of FTS for harm reduction strategies approved by the government such as drug checking. The market for FTS has expanded rapidly in the US and Canada. However, there is no regulatory oversight by either government to ensure proper function of FTS that are being marketed for drug checking. MAIN BODY: Many brands of FTS have rapidly entered the harm reduction market, creating concerns about the reproducibility and accuracy of their performance from brand to brand and lot to lot. Some examples are provided in this Comment. Similar problems with product quality were observed in the mid 2000's when lateral flow immunoassays for malaria were funded in many countries and again in 2020, when COVID-19 tests were in huge demand. The combination of high demand and low levels of regulation and enforcement led some manufacturers to join the goldrush without adequate field testing or quality assurance. We argue that the harm reduction community urgently needs to set a lot checking program in place. A set of simple protocols for conducting the tests and communicating the results have been developed, and are described in the following Perspectives paper in this issue. CONCLUSION: In the absence of governmental regulation and enforcement, the harm reduction community should implement a FTS lot checking program. Based on previous experience with the malaria diagnostic lot checking program, this inexpensive effort could identify products that are not suitable for harm reduction applications and provide valuable feedback to manufacturers. Dissemination of the results will help harm reduction organizations to ensure that FTS they use for drug checking are fit for the purpose.

Broad-spectrum and sensitive screening of more than 1000 compounds in equine urine using liquid chromatography/high-resolution mass spectrometry.

RATIONALE: To uphold the integrity of horseracing and equestrian sports, it is critical for an equine doping control laboratory to develop a comprehensive screening method to cover a wide range of target substances at the required detection levels in equine urine. METHODS: The procedure involved the enzymatic hydrolysis of 3 mL urine samples followed by solid-phase extraction using HF Bond Elut C18 cartridge. The resulting extracts were then separated on a C18 reversed-phase column and analyzed using liquid chromatography/high-resolution mass spectrometry (LC/HRMS) in both electrospray ionization positive and negative modes in two separate injections. The analytical data were obtained in full scan and product ion scan (PIS) modes in an 11 min LC run. RESULTS: The method can detect 1011 compounds (in both positive and negative ion modes). Over 95% of the target compounds have limits of detections (LODs) ≤10 ng/mL, and more than 50% of the LODs are ≤0.5 ng/mL. The lowest LOD can reach down to 0.01 ng/mL. The applicability of the method was demonstrated by the successful detection of prohibited substances in overseas and domestic equine urine samples. CONCLUSIONS: We have successfully developed a regular screening method for equine urine samples that can detect more than 1000 compounds at sub-ppb levels in both positive and negative ion modes with full scan and PIS using LC/HRMS. Furthermore, this method can theoretically be expanded to accommodate an unlimited number of prohibited substances in full-scan mode.

A Review of Wastewater-Based Epidemiology Studies for the Assessment of Over-the-Counter Medicines Used as Recreational Drugs: The Example of Dextromethorphan.

The 'recreational use' of selected over-the-counter (OTC) medicines is an unofficial activity. The traditional surveys assessing the use of drugs are affected by the bias of underreporting and are thus unreliable. The development of analytical techniques helps to monitor the substances at trace levels, such as in wastewater, and might be applied to estimate the consumption of an analyte of interest and ensure additional, evidence-based information complementary to population surveys. We reviewed studies focused on evaluating the estimated consumption of drugs as a reliable and unbiased source of evidence-based information (called wastewater-based epidemiology, WBE) to monitor the scale of this phenomenon. We found there is a need to test not only narcotics in the environment but also medicines that may be abused or recreationally used. The reviewed studies show methods that might provide reliable information about consumption of drugs, narcotics, and OTC medications for proposing targeted, preventive actions. Moreover, as all the selected studies were based on mass spectrometry, there is a potential to include the dextromethorphan and/or related compounds as part of the screening for narcotics and OTC drugs that can be socially harmful, overused, or misused. This article reviews the analytical methods for detecting dextromethorphan and/or its transformation products in environmental water samples.

Dilute-and-shoot approach for the high-throughput LC-MS/MS determination of illicit drugs in the field of wastewater-based epidemiology.

The determination of illicit drugs in urban influent wastewater (IWW) enables the monitoring of spatial and temporal drug usage trends and assessment of community lifestyle habits. The increasing number of wastewater surveillance studies has emphasized the necessity for the development of rapid, high-throughput methods that maintain high quality data. This work evaluates the use of a dilute-and-shoot methodology, based on direct injection (DI) of centrifuged samples, as an alternative approach to the widely applied sample pre-treatment based on solid-phase extraction, for the liquid chromatography-tandem mass spectrometry determination of seven widely consumed illicit drugs and their metabolites in IWW (amphetamine; cocaine metabolite, benzoylecgonine; ketamine; 3,4-methylenedioxymethamphetamine (MDMA); methamphetamine; cannabis metabolite, 11-nor-9-carboxy-delta-9-tetrahydrocannabinol (THCCOOH); heroin metabolite, 6-acetylmorphine (6-MAM)). Comparison of both approaches in terms of matrix effects, sensitivity and accuracy, demonstrates the DI method suitability to correctly quantify these analytes in IWW, with a limit of quantification lower than 30 ng L-1 for most compounds. After validation of the method and participation in an interlaboratory exercise, the DI method was applied to the analysis of 54 IWW samples collected from different Spanish wastewater treatment plants. Additionally, quality controls were incorporated in each analysis batch to support the DI method applicability and robustness. The use of a 10 µL-DI reduces time-consuming sample preparation, analysis time and measurement uncertainty. Moreover, it supports green chemistry by reducing the consumption of organic solvents and it facilitates logistics by collecting, transporting, and storing less sample volume. The methodology is therefore especially appropriate for monitoring illicit drugs in large wastewater-based epidemiology sampling campaigns or when fast near real-time results are needed.

Sensitivity, specificity, and discordance with self-report of nail sample testing for alcohol and cannabis.

BACKGROUND: Nails accumulate the alcohol metabolite, ethyl glucuronide (ETG), and the cannabis metabolite, carboxy- delta-9-THC over 3-6 months. Few studies have examined nail toxicology testing's sensitivity and specificity and the agreement between nail testing and self-reported alcohol and marijuana use. METHODS: In an ongoing clinical trial, 1101 veterans completed initial telephone questionnaires and were then asked to mail nail clippings for substance use analysis. We examined sensitivity and specificity of ETG and carboxy- delta-9-THC in nails compared to self-report of alcohol use patterns (the AUDIT-C) and substance-related harms (alcohol and THC subscales of the ASSIST). We then examined factors associated with discordance between nails and self-report. RESULTS: Almost two-thirds (707/1101) of respondents mailed in nail clippings. Those with returned nails were disproportionately married, white race, older, and less depressed. At a threshold of 8pg/mg, sensitivity was only.50 to detect risky alcohol use and.49 to detect alcohol-related issues. Sensitivity for marijuana issues was only.61. Specificity was greater than.77 for all measures. Factors associated with positive nails/negative self-report (i.e. false positives) for risky alcohol use on the Audit-C included more pain and being unmarried; false positive nails for alcohol-related issues on the ASSIST were associated with being unmarried and non-Hispanic ethnicity. False positive nails for THC-related issues on the ASSIST were associated with being African American, Hispanic, and having had legal issues. CONCLUSIONS: At standard cut-offs, nail measures had low sensitivity and higher specificity. The groups who disproportionately submit positive nails/negative self-report could have substance use patterns not adequately captured by self-report, inaccurate self-report due to social pressures, or distinct drug metabolism.

Assessment of a Single Quadrupole Mass Spectrometer Combined with an Atmospheric Solids Analysis Probe for the On-Site Identification of Amnesty Bin Drugs.

The surging number of people who abuse drugs has a great impact on healthcare and law enforcement systems. Amnesty bin drug analysis helps monitor the "street drug market" and tailor the harm reduction advice. Therefore, rapid and accurate drug analysis methods are crucial for on-site work. An analytical method for the rapid identification of five commonly detected drugs ((3,4-methylenedioxymethamphetamine (MDMA), cocaine, ketamine, 4-bromo-2,5-dimethoxyphenethylamine, and chloromethcathinone)) at various summer festivals in the U.K. was developed and validated employing a single quadrupole mass spectrometer combined with an atmospheric pressure solids analysis probe (ASAP-MS). The results were confirmed on a benchtop gas chromatography-mass spectrometry instrument and included all samples that challenged the conventional spectroscopic techniques routinely employed on-site. Although the selectivity/specificity step of the validation assessment of the MS system proved a challenge, it still produced 93% (N = 279) and 92.5% (N = 87) correct results when tested on- and off-site, respectively. A few "partly correct" results showed some discrepancies between the results, with the MS-only unit missing some low intensity active ingredients (N-ethylpentylone, MDMA) and cutting agents (caffeine, paracetamol, and benzocaine) or detecting some when not present. The incorrect results were mainly based on library coverage. The study proved that the ASAP-MS instrument can successfully complement the spectroscopic techniques used for qualitative drug analysis on- and off-site. Although the validation testing highlighted some areas for improvement concerning selectivity/specificity for structurally similar compounds, this method has the potential to be used in trend monitoring and harm reduction.

Simultaneous chemo- and enantio-separation of 2-, 3- and 4-chloro-methcatinones by high-performance liquid chromatography-tandem mass spectrometry and its application to oral fluid samples.

A method of analysis was developed for the simultaneous chemo- and enantioseparation of 2-, 3-, and 4-chloromethcathinones by high-performance liquid chromatography tandem mass-spectrometry. The fast method enables the reliable identification of positional isomers of chloromethcathinones in biological samples. In addition, the same method can be used for the enantioselective quantitative determination of one of these compounds and its major phase-1 metabolites in biological fluids. The developed method was applied to oral fluid samples collected by police during routine random traffic control in Belgium from January to November, 2023. It was found that 3-CMC was more frequently abused compared to 4-CMC. Although some differences were observed between the concentrations of enantiomers in OF, most likely the drugs were abused in the racemic form. No abuse of 2-CMC was detected at the timepoint of sample collection.

Ambient ionization mass spectrometry provides screening of selective androgen receptor modulators.

Ambient ionization mass spectrometry allows for analysis of samples in their natural state, i.e., with no sample pre-treatment. It can be viewed as a fast, simple, and economical analysis, but its main disadvantages include a lower analytical performance due to the presence of complex sample matrix and the lack of chromatographic separation prior to the introduction of the sample into the mass spectrometer. Here we present an application of two ambient ionization mass spectrometry techniques, i.e., Desorption Atmospheric Pressure Photoionization and Dielectric Barrier Discharge Ionization, for the analysis of known Selective Androgen Receptor Modulators, which represent common compounds of abuse in professional and semiprofessional sport. Eight real samples of illegal food supplements, seized by the local law enforcement, were used to test the performance of the ambient mass spectrometry and the results were validated against a newly developed targeted LC-UV-MS/MS method performed in multiple reaction monitoring mode with an external calibration for each analyte. In order to decide whether or not the compound can be declared as present, we proposed a system of rules for the interpretation of the obtained spectra. The criteria are based on mass spectrum matching (5-10 ppm accuracy from the theoretical exact mass and a correct isotopic pattern), duration of the mass signal (three or five consecutive scans, depending on the instrumentation used), and intensity above the background noise (threefold increase in intensity and absolute intensity above 5E4 or 1E5, depending on the instrumentation). When applying these criteria, good agreement was found between the tested methods. Ambient ionization techniques were effective at detecting SARMs at pharmacologically relevant doses, i.e., approximately above 1 mg per capsule, although they may fail to detect lower levels or isomeric species. It is demonstrated that when adhering to a set of clear and consistent rules, ambient mass spectrometry can be employed as a qualitative technique for the screening of illegal SARMs with sufficient confidence and without the necessity to perform a regular LC-MS analysis.

Racial Disparities in Newborn Drug Testing After Implementation of Question-Based Screening for Prenatal Substance Use.

OBJECTIVE: To examine the association of universal question-based screening for prenatal substance use on racial inequities in prenatal and newborn drug testing. METHODS: We conducted a retrospective cohort study of 32,802 live births of patients receiving prenatal care at an academic medical center in the midwestern United States from 2014 to 2022, before and after implementation of question-based screening in 2018. Primary outcomes included prenatal and newborn drug test orders. Logistic regression models using a generalized estimating equation framework assessed associations with question-based screening and results, birthing parent age, race, ethnicity, marital status, and insurance type. Charts of patients who indicated difficulties stopping substance use were audited for guideline-directed care. RESULTS: A total of 12,725 of 14,992 pregnant people (85.3%) received question-based screening. Implementation of question-based screening was associated with a decrease in prenatal urine test orders (5.0% [95% CI, 4.6-5.3%] before implementation, 3.1% [95% CI, 2.8-3.4%] after implementation; P <.001), with Black birthing parents having the largest reduction in prenatal urine drug testing (10.3% [95% CI, 9.0-11.7%] before implementation, 4.9% [95% CI, 3.9-5.9%] after implementation). However, rates of newborn drug testing did not change (4.7% [95% CI, 4.4-5.0%] before implementation, 4.5% [95% CI, 4.2-4.8%] after implementation; P =.46), and clinicians continued to order significantly more newborn drug tests for newborns of Black birthing parents compared with other race and ethnicity groups. CONCLUSION: Implementation of question-based screening for substance use in pregnancy was associated with decreased prenatal urine drug testing but no change in overall newborn drug testing or racial inequities in newborn drug testing for Black birthing people. Further policy efforts are warranted to improve substance use treatment and to eliminate racial inequities in punitive policies such as newborn drug testing and subsequent child protective services reporting.

A Retrospective Cohort Study of Disparities in Urine Drug Testing During the Perinatal Period in an Urban, Academic Medical Center.

The purpose of this study was to evaluate disparities in urine drug testing (UDT) during perinatal care at a single academic medical center. This retrospective cohort study included patients who had a live birth and received prenatal care at our institution between 10/1/2015 and 9/30/2020. The primary outcomes were maternal UDT during pregnancy (UDTPN) and UDT only at delivery (UDTDEL). Secondary outcomes included the number of UDTs (UDTNUM) and the association between a positive UDT test result and race/ethnicity. Mixed model logistic regression and negative binomial regression with clustering based on prenatal care locations were used to control for confounders. Of 6,240 live births, 2,265 (36.3%) and 167 (2.7%) received UDTPN and UDTDEL, respectively. Black (OR 2.09, 95% CI 1.54-2.84) and individuals of Other races (OR 1.64, 95% CI 1.03-2.64) had greater odds of UDTPN compared to non-Hispanic White individuals. Black (beta = 1.12, p < 0.001) and Hispanic individuals (beta = 0.78, p < 0.001) also had a positive relationship with UDTNUM. Compared to individuals with non-Medicaid insurance, those insured by Medicaid had greater odds of UDTPN (OR 1.66, 95% CI 1.11-2.49) and had a positive relationship with UDTNUM (beta = 0.89, p < 0.001). No significant associations were found for UDTDEL and race/ethnicity. Despite receiving more UDT, Black individuals were not more likely to have a positive test result compared to non-Hispanic White individuals (OR 0.95, 95% CI 0.72-1.25). Our findings demonstrate persistent disparities in substance use testing during the perinatal period.

Predictors of urine toxicology and other biologic specimen missingness in randomized trials of substance use disorders.

BACKGROUND: High levels of missing outcome data for biologically confirmed substance use (BCSU) threaten the validity of substance use disorder (SUD) clinical trials. Underlying attributes of clinical trials could explain BCSU missingness and identify targets for improved trial design. METHODS: We reviewed 21 clinical trials funded by the NIDA National Drug Abuse Treatment Clinical Trials Network (CTN) and published from 2005 to 2018 that examined pharmacologic and psychosocial interventions for SUD. We used configurational analysis-a Boolean algebra approach that identifies an attribute or combination of attributes predictive of an outcome-to identify trial design features and participant characteristics associated with high levels of BCSU missingness. Associations were identified by configuration complexity, consistency, coverage, and robustness. We limited results using a consistency threshold of 0.75 and summarized model fit using the product of consistency and coverage. RESULTS: For trial design features, the final solution consisted of two pathways: psychosocial treatment as a trial intervention OR larger trial arm size (complexity=2, consistency=0.79, coverage=0.93, robustness score=0.71). For participant characteristics, the final solution consisted of two pathways: interventions targeting individuals with poly- or nonspecific substance use OR younger age (complexity=2, consistency=0.75, coverage=0.86, robustness score=1.00). CONCLUSIONS: Psychosocial treatments, larger trial arm size, interventions targeting individuals with poly- or nonspecific substance use, and younger age among trial participants were predictive of missing BCSU data in SUD clinical trials. Interventions to mitigate missing data that focus on these attributes may reduce threats to validity and improve utility of SUD clinical trials.