Prospective Cohort Study of Fentanyl Test Strip Use and Distribution in Three States: The Stay Safe Study Protocol and Implementation Recommendations for Researchers

doi:10.21203/rs.3.rs-4870101/v1

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Prospective Cohort Study of Fentanyl Test Strip Use and Distribution in Three States: The Stay Safe Study Protocol and Implementation Recommendations for Researchers

https://doi.org/10.21203/rs.3.rs-4870101/v1

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Background

The Stay Safe Study is the first observational prospective cohort study investigating fentanyl test strip (FTS) use by people who use drugs (PWUD) and distribution by harm reduction organizations in three states (Kentucky, New York, and Ohio). The purpose of this paper is to describe the study design, along with implementation success and challenges. A related goal is to provide recommendations and encourage researchers to undertake multi-state and multilevel studies of FTS use and distribution.

Methods

The protocol has one primary, five secondary, and three exploratory objectives. From May-December 2023, the study collected survey, interview, and oral fluid drug test (ODT) data with the primary population of PWUD attending community harm reduction organizations that distribute FTS. We collected survey and interview data with a secondary population of community harm reduction organizations that have a distribution relationship to FTS. There was no intervention and the study did not distribute FTS.

Results

The full study sample was 732 PWUD participants (97.6% of the target) from 1,156 enrolled PWUD participants. Enrolled PWUD participants completed a baseline assessment and at least two of four weekly survey assessments. A subset of participants completed a one-time ODT (n=269) and one-on-one semi-structured interviews (n=120). From the secondary population of 36 harm reduction organizations, employees of 28 organizations (78%) in 22 counties across 3 states completed a web-based survey and employees of 24 organizations (66.7%) completed an interview. Study findings will be presented in subsequent publications.

Conclusion

The study team successfully enrolled a large sample of PWUD and organizational participants in three states, followed a cohort of PWUD participants and generated rich data using three types of instruments. Factors contributing to implementation success include drawing on the community expertise of the parent HEALing Communities Study, selecting incentive amounts that acknowledged the time and expertise of PWUD participants, centralizing survey data collection, and tracking implementation challenges and solutions. Areas of implementation complexity included conducting research on site at community harm reduction organizations, facilitating timely incentive payments, overseeing study staff, and returning ODT results to PWUD participants.

Fentanyl test strips

Fentanyl

Opioids

Stimulants

Harm reduction

Substance use

Overdose prevention

People who use drugs

Community organizations

The ongoing overdose crisis in the United States has exacted an increasingly heavy toll on public health. Since 1999, more than 1.1 million people have died from a drug overdose in the United States [1, 2]. Drug overdose deaths involving synthetic opioids, excluding methadone, particularly illicitly manufactured fentanyl, increased from 57,834 in 2021 [3] to 74,702 in 2023 [4]. Overdose deaths from fentanyl are a serious public health threat because fentanyl is present in illicit opioids, stimulants, crushed pills, recreational substances such as MDMA (also known as Ecstasy), and counterfeit medications [3, 5–7].

Fentanyl test strips (FTS) are a low-barrier drug-checking tool that can detect multiple fentanyl analogs in a range of substances at the point of consumption [8–12]. While investigation of FTS practices has grown rapidly since 2016 [13], evidence derives primarily from single-instrument feasibility and acceptability studies using qualitative or quantitative designs and small sample sizes (n = 11–93) of PWUD [8–11, 14–21], which limit generalizability. Most FTS studies have been conducted at a single site, typically a syringe service program or other harm reduction service provision sites. At the time of this writing and confirmed by a recent scoping review [13], just four out of 26 FTS studies have sample sizes of PWUD > 100 (n = 105–426) [8, 12, 22], and all but two [12, 22] were conducted in a single state or province. Two studies tested an FTS intervention [20, 23], and another FTS study used a urinalysis test to investigate concordance of self-reported fentanyl consumption with biomarker results [24].

Findings are mixed on whether PWUD who obtain a positive FTS result modify their drug use behaviors [8, 9], suggesting the need to look more closely at the impact of FTS use, risk perception, and behavior change [25]. A single study using a cross-sectional, mixed-methods design compared substance use behaviors of PWUD who do and do not use FTS [14]. Researchers leading this study found that FTS use by PWUD is associated with both safer behaviors (e.g., using less drug supply than normal) and riskier behaviors (e.g., using more drug supply than normal). Significant gaps remain in understanding whether use of FTS by PWUD is associated with a reduction in overdose risk [12, 19, 20, 23]. There is limited evidence on community-based organizations and FTS: their distribution strategies, the reach of their FTS programs to populations at risk of fentanyl-related overdose, and their educational strategies with PWUD for correct FTS use and overdose prevention. Understanding FTS use and distribution with a multi-state study is critical for informing intervention strategies and to optimize community-based distribution of FTS as an overdose prevention strategy [26].

In this paper, we present the study protocol for the Stay Safe Study. The Stay Safe Study is the first prospective cohort study of FTS use and distribution conducted in three states (Kentucky [KY], New York [NY], and Ohio [OH]). The primary goal of this paper is to describe the study design and implementation successes and challenges of this complex study design. We also provide recommendations to researchers [27] for developing more robust studies of the effectiveness and distribution of drug-checking tools such as FTS [26].

Study structure and development

The Stay Safe Study is an ancillary study of the HEALing Communities Study (HCS), a community-level, two-arm, cluster randomized clinical trial evaluating the effectiveness of the Communities That HEAL intervention on reducing opioid-related overdose fatalities in 67 communities in four states [28]. The Stay Safe Study team consists of members from three state teams, a data coordinating center (DCC) led by RTI International, and scientists with the National Institute on Drug Abuse (NIDA) and the Substance Abuse and Mental Health Services Administration (SAMHSA). The DCC facilitated study meetings, coordinated central IRB submission, programmed surveys, hosted survey data collection on its portal, conducted quantitative data analysis, and coordinated the study-wide qualitative data analysis team. The study received IRB approval from Advarra (Pro00068304) on March 16, 2023, with additional IRB approval from Columbia University for the NY team on August 29, 2023. Data collection took place from May to December 2023.

Definition of terms

Direct service provision sites: The service locations of community partner organizations in the three states (see definition of “partner organization” below). Sites include a range of fixed and mobile locations that deliver harm reduction services (e.g., buildings, mobile vans, and parking lots adjacent to these sites), including fentanyl test strips. These sites served as the primary data collection locations.

Eligible: All participants from the primary population of people who use drugs who completed the Screener Survey and met all eligibility criteria.

Enrolled: All participants from the primary population of people who use drugs who completed the Baseline Survey.

FTS Sample: All participants from the primary population of people who use drugs in the Full Sample who used fentanyl test strips at least once during the 28-day observation period.

Full Sample: All participants from the primary population of people who use drugs who completed the Baseline Survey, completed at least two of the four Weekly Surveys, and reported drug use at least once during the 28-day observation period.

ODT Sample: All participants from the primary population of people who use drugs who completed the Baseline Survey, completed the Oral Fluid Test Survey, and had valid results for the Oral Fluid Drug Test.

Organizational participants: Community-based harm reduction organizations that were recruited in the three study states, met one of four potential distribution relationships to fentanyl test strips, and participated in the study as a secondary population.

Partner organizations: Harm reduction organizations (e.g., a community clinic, syringe service program, or public health department) that partnered with state research teams to host PWUD data collection at their direct service provision sites.

Qualitative Sample: All participants from the primary population of people who use drugs who completed the qualitative interview.

Screened: All participants from the primary population of people who use drugs who completed the Screener Survey.

Study team: Scientists and research study staff from the three states, the study data coordinating center, the National Institute on Drug Abuse, and the Substance Abuse and Mental Health Services Administration.

Study rationale

The primary impetus for the Stay Safe Study was the need for empirical evidence of the effectiveness of FTS use in reducing overdose risk. That investigation was beyond the scope of the HCS. The current study aimed to robustly assess the evidence in support of FTS use with a well-designed, well-powered, multilevel study implemented in diverse settings across three states. The decision to undertake this ancillary study to the HCS was facilitated by Substance Abuse and Mental Health Services Administration (SAMHSA) approval for use of FTS by federally funded researchers in April 2021 [29]. A second impetus was the need for multi-state study designs that investigated how multilevel contextual factors shape FTS distribution and use across states [26]. For example, drug paraphernalia statutes may criminalize possession and/or distribution of FTS and may directly implicate the procurement and distribution strategies of harm reduction organizations, along with access to FTS by PWUD [30]. While FTS are legal to distribute and possess in NY, criminalization statutes in KY and OH were in place until 2023, creating a disparate legal landscape that may shape distribution, access and use across the three states; these contextual factors required further investigation.

Populations and instruments

The study recruited two distinct populations. The primary population was PWUD who attended the direct service provision sites of partner organizations that distribute FTS at the time of our study. The study used three data collection instruments with PWUD participants: web-based surveys, one-on-one semi-structured interviews, and an oral fluid drug test (ODT) (see PWUD data collection). The study invited persons with lived experience of drug use (PWUD and harm reduction employees) to review instruments and revise them for appropriate length and language.

The second population was harm reduction organizations that had one of four distribution relationships to FTS (see inclusion criteria for organizational participants) at the time of our study. The study used two data collection instruments with organizational participants: a survey and one-on-one semi-structured interviews.

Objectives and outcomes

The study has one primary, five secondary, and three exploratory objectives (Table 1). There is no intervention, and the study did not distribute FTS to participants.

The primary objective of the Stay Safe Study is to test the hypothesis that PWUD who report FTS use at baseline also report using a higher number and frequency of overdose risk reduction behaviors (ORRBs) during the 28-day observation period compared to PWUD who do not report FTS use at baseline. An ORRB is any behavior by an individual, acting alone or with others, which may reduce the risk of overdose (fatal or non-fatal) from substance use. Examples of ORRBs among PWUDs are consuming less of the substance [31, 32], consuming with others [31, 33, 34], using a small amount of the substance to test potency and toxicity [31, 34, 35], discarding the substance if fentanyl is present [32], and having naloxone nearby [8, 20, 32, 33, 35].

[Insert Table 1 here]

The study includes five secondary objectives. The first four investigate behaviors of PWUD participants and the fifth investigates practices of organizational participants: (1) among PWUD who use FTS at baseline, examine the association between their FTS results and overdose risk reduction behaviors; (2) examine the concordance between self-reported substance use among PWUD and their ODT results; (3) examine the association between FTS use at baseline by PWUD and the occurrence of a non-fatal overdose during the 28-day observation period; (4) examine the perspectives and experiences of FTS use among PWUD; and (5) examine the perspectives and experiences of organizations distributing FTS, facilitators and barriers to FTS distribution, and cost of FTS strategies. Secondary objectives are measured by the following outcomes: (1) Number of ORRBs following each FTS use on each day during the 28-day observation period; (2) ODT-positive for fentanyl (yes/no); and (3) Self-reported non-fatal overdose on each day drugs are used during the 28-day observation period (yes/no). Secondary objectives (4) and (5) were measured qualitatively.

Sample, setting, and procedures

Team staffing models

Two states hired study staff living in communities near data collection sites to manage advertising, recruitment, and data collection. A third state used an engaged approach by hiring employees of partner organizations who worked at direct service provision sites to advertise the study, recruit PWUD participants, and collect data. Employees of these sites had previously completed research ethics training and had developed rapport with their clientele [27, 36]. This staffing approach supported the team by having employees trusted by study participants conduct recruitment and eliminating extensive travel to data collection sites. Throughout this paper, we refer to all team members as “study staff.”

Partner organizations

The study recruited a convenience sample of 14 partner organizations to host research activities at their harm reduction direct service provision sites (KY=5, NY=3, OH=6). Eleven of the 14 partner organizations (78.6%) are located in metropolitan areas (core or high commuting) and three (21.4%) are located in micropolitan area cores (primary flow within an Urban Cluster of 10,000 to 49,999) according to the US Department of Agriculture Rural-Urban Commuting Area Codes [37].

Partner organizations were any community-based harm reduction organization that had a fixed direct service provision site (including parked vans and adjacent parking lots) or a mobile van service. All were required to distribute FTS and serve a clientele that included (but was not limited to) PWUD. To recruit partner organizations, state teams approached organizations that were (1) community coalition members in the parent HCS and/or (2) part of their research networks. Teams also used convenience sampling to identify interested organizations. Compensation models for partner organizations to host and/or conduct research activities differed by state. One state provided $2,000 to each organization with an additional $25 for each individual screened and $30 for each organizational participant that completed an interview. A second state provide a flat $5,000 to each partner organization that hosted data collection. A third state provided no compensation. In addition, some partner organizations had policies prohibiting receipt of compensation.

PWUD participants

Inclusion criteria

PWUD participants were required to be 18 years of age or older, able to read and speak English, able to understand and provide informed consent, and residing in KY, NY, or OH at enrollment and during the 28-day observation period. Participants were eligible for enrollment If they had used any of the following substances over the previous 30 days: heroin; fentanyl; powder cocaine; crack or rock cocaine; methamphetamine; pain pills or opioids not prescribed to the participant (such as hydrocodone, or oxycodone); benzodiazepines not prescribed to the participant (such as alprazolam or clonazepam); or stimulants not prescribed to the participant (such as amphetamine or methylphenidate). The PWUD participant cohort consisted of (1) individuals who self-reported FTS use in the 30 days prior to the baseline survey or planned FTS use in the 28-day observation period and (2) individuals who self-reported not using FTS in the 30 days prior to the baseline survey and had no plans to use FTS in the 28-day observation period.

Incentive payments.

The study paid PWUD participants per data collection event [38] (Table 2). Although cash payments can promote the dignity of participants [39], all teams selected card payment systems because they offered significant benefits to cash (e.g., electronic tracking and increased safety for all). One card system offered additional functionality to major brand payment cards and was selected by two state teams. This card system allowed teams to program payment amounts tied to unique data collection events in advance, which reduced error.

[Insert Table 2 here]

Study advertising and setting

The study team reviewed draft advertising materials for inclusivity and agreed on a single poster with images that included persons of color and person-first language. Teams advertised the study at indoor and outdoor direct service provision sites of the 14 partner organizations, which became the study data collection sites. The KY and OH teams began advertising in May 2023; NY followed in August 2023. At each data collection site, study staff recruited individuals, explained study purpose and procedures, obtained informed consent, and collected data for the screener, baseline, weekly, and ODT surveys, as well as the oral swab for the ODT (see PWUD data collection). One state team recruited PWUD participants in the direct service provision site’s mobile van unit, allowing for an expanded outreach of diverse participants.

Estimating recruitment targets

The DCC calculated a full sample target of N=750 PWUD for the study. The full sample was defined as total number of enrolled PWUD participants who had completed (1) the screener and baseline surveys plus (2) any two of four weekly surveys (Figure 1). Because state teams knew in advance that not all enrolled PWUD participants would complete four weekly surveys during the observation period, they intentionally recruited and enrolled a large number of PWUD participants to meet this full sample target.

[Insert Figure 1 here]

PWUD data collection

Screener, baseline, and weekly surveys

Study staff used a web-based screener survey loaded on electronic tablets with interested individuals at the data location sites to determine their study eligibility (Table 2). Those who did not meet the eligibility criteria were compensated $10 for their time, thanked for their participation, and excluded.

With eligible individuals who chose to enroll, study staff reviewed the data collection timeline and events, then completed verbal and electronic informed consent. Immediately afterwards, eligible individuals completed a baseline survey that collected 1) participant demographics (e.g., race, ethnicity, gender identity, sexual orientation, marital status, educational attainment, health insurance status) and 2) information about substances used in the past 30 days, frequency of use, route of administration, and their baseline knowledge and awareness of FTS. The survey included questions on FTS prior use and previous education on how to use FTS. The final portion asked about use of ORRBs (e.g., having naloxone nearby), mixing of drugs, and overdose incidence in the prior 30 days, and were asked to provide contact information (e.g., email address, mobile or home telephone numbers, and/or Facebook messaging coordinates) to receive reminders and instructions for subsequent data collection.

After completing the baseline survey, the individual was deemed an enrolled PWUD participant (Figure 1). Enrolled PWUD participants were invited to return to the data collection site every seven days for a maximum of four times to complete a weekly survey during their 28-day observation period. Participants were eligible to complete each weekly survey either at the recruitment site or remotely in a setting that was deemed private with an Internet connection by logging into the DCC study survey portal with their username and password.

The weekly survey asked about FTS use, ORRBs, and use of specific drugs for each day of the past week (i.e., heroin, fentanyl, powder cocaine, crack or rock cocaine, methamphetamine, pain pills or opioids not prescribed to the participant, benzodiazepines not prescribed to the participant, and stimulants not prescribed to the participant). For each day that the participant indicated drug use in the weekly survey, they were asked to indicate which drugs they used, whether they used FTS, reasons they did or did not use FTS, and the results of FTS use for the first two FTS testing events on that day. Participants were also asked to identify ORRBs they used. After indicating the result from up to two daily instances of FTS use (positive, negative, or undetermined), participants were asked about their drug use behaviors following the FTS result(s).

Oral fluid drug test (ODT)

Participants were invited to complete an ODT in the Day 26-37 window after their study enrollment and after their last weekly survey window had closed. The study selected the ODT over a urine drug test because the ODT was easy to implement, and samples did not require refrigeration. There was no study target for the number of completed ODTs (see PWUD data collection). ODT data collection combined an in-person oral swab with an electronic survey asking participants to identify all substances consumed in the past 48 hours. Both the oral swab and survey were self-administered.

Study staff did not mention the ODT to participants until after the fourth weekly survey occurred to minimize changes to routine substance use practices. A separate informed consent process and form were used to allow participants to opt in. Each participant was asked in the ODT survey whether they wished to receive a summary report of their drug test. Study staff returned ODT results to PWUD participants in person and/or by telephone.

The study convened medical directors from each state to discuss best approaches in each state to administering the ODT. The study contracted Millennium Health to provide ODT kits and shipping materials to each state team and to conduct the laboratory analysis of collected samples. All ODT samples were mailed by study staff, processed by Millennium Health, and results returned to the DCC were uploaded to the study portal.

Interview

The study team set a target of 120 completed one-on-one semi-structured interviews with PWUD (40 per state). Experienced qualitative researchers conducted interviews, which lasted up to an hour, with a subset of participants from the enrolled PWUD sample. Interviews explored participant awareness of fentanyl in their supply, attitudes towards FTS, FTS use patterns, barriers and facilitators to obtaining FTS, and use of ORRBs. Interviews also solicited advice participants would give about FTS to a friend who uses drugs, recommendations for FTS programs, and a change they would make to prevent fatal fentanyl-related overdose.

To include diverse perspectives in the interview sample, state team leads developed a purposive sampling frame to optimize representation of underrepresented groups. Leads identified 28 demographic and substance use-related characteristics (29 characteristics in NY to include xylazine test strip status) across seven variables in the quantitative survey (eight in NY to include xylazine test strip status) on which to sample (Table 3). These variables were theoretically driven on the basis of known risk and access differences between groups [40, 41]. Guided by state-specific frequency tables for the 28 characteristics and expert judgment, team leads prioritized recruiting eligible participants from variable groups with the smallest survey frequencies. Once the PWUD interview samples were selected for each state, the interviewers selected the appropriate interview guide that corresponded to the participant’s two-cell FTS status.

[Insert Table 3 here]

FTS subgroup status was assigned to each participant based on their responses to questions about FTS use in (1) the baseline survey, and (2) the weekly surveys. Those responses constituted a two-by-two subgroup designation: Subgroup 1 (N-N): participants who did not anticipate using FTS at baseline and did not use FTS throughout the 28-day observation period; Subgroup 2 (Y-Y): participants who anticipated using FTS at baseline and did use FTS during the 28-day observation period; Subgroup 3 (N-Y): participants who did not anticipate using FTS at baseline and reported using FTS during the 28-day observation period; and, Subgroup 4 (Y-N): participants who anticipated using FTS at baseline and did not report using FTS during the 28-day observation period. Each interview guide corresponded to one of four subgroups, with a target of 30 participants in each subgroup. Domains and questions in each guide were tailored to each FTS subgroup. Interviewers used the PWUD interview guide that corresponded to the FTS subgroup status of the participant they interviewed.

Organization participants

Sample and setting

The study recruited a secondary population of 28 community harm reduction organizations, including the 14 partner organizations that hosted data collection in the three states. The purpose was to identify multilevel facilitators and barriers to FTS distribution, reach of their FTS programs to at-risk populations, costs of FTS purchasing and distribution, and the role of contextual factors in FTS use and ORRBs among PWUD. Study staff used email and phone communication to advertise the study to potential organization-level participants, and conducted all data collection remotely (phone, online surveys, or Zoom interview). Study staff used a separate informed consent process and electronic consent form for the survey and interview.

Inclusion criteria

Harm reduction organizations were eligible to participate in the survey and interview if they reported any of the following: (1) currently distributing FTS, (2) had distributed FTS in the past but stopped, (3) intending to distribute FTS in the next year, or (4) intended to distribute FTS but encountered barriers and never started. All partner organizations that participated de facto met inclusion criterion (1) (currently distributing FTS). The study team chose broad inclusion criteria to recruit a large number of organizational participants that had encountered a range of legal, policy, and financial barriers for FTS distribution, such as criminalization statutes and restrictive harm reduction climates. Leads or employees of organizations who had (1) sufficient knowledge of the organization, and (2) were involved in FTS distribution decisions were eligible to participate.

Incentive payments

States tailored incentives to organizational participants based on past practice and expert judgement. Two states offered incentive payments to organizations for survey and/or interview participation, and one state offered no incentive payments.

Organization data collection

Survey

Using an emailed invitation script, each state team invited organizational participants to complete a web-based survey hosted on the study portal. The survey solicited organization location, self-classification, staffing size, population(s) served, and FTS program details (e.g., costs and number ordered monthly).

Interview

Each team invited the same organizations to participate in a one-on-one semi-structured interview led by an experienced qualitative researcher. The interviewer solicited information about policies and practices for FTS distribution including changes over the last year, strategies to reach at-risk and minority populations, and client educational practices. They also solicited recommendations about FTS distribution, an overarching message about FTS, and changes recommended to prevent PWUD from having a fatal overdose from fentanyl.

Educational materials

Interviewers also asked each organization to provide copies of FTS educational materials and resources available in any format (e.g., electronic and hard documents, videos links, and links to social media advertising and messaging) used to communicate FTS availability or instructions for use.

Sample Size, Data Monitoring, and Analysis

Sample size

A sample size of 750 PWUD who completed the baseline survey, at least two of the four weekly surveys, and used drugs at least once during the 28-observation period was selected to ensure that a 0.19-0.43 standard deviation difference in the mean of the daily composite score across the 28-day observation period between PWUD who self-reported FTS use at baseline and PWUD who self-reported no FTS use at baseline could be detected with 80% power. This sample size was determined by assuming an average of 30% missing response across the 28-day observation period, 0.80 correlation between any two of the daily scores measured on the same participant, and a two-sided significance level of 0.05. Estimates were based on a Generalized Estimation Equation test of the time-averaged difference of two groups in a repeated measured design of a continuous outcome (available in PASS 2022).

Data monitoring

Remote data monitoring was conducted by the DCC throughout the study to monitor enrollment and data quality. Any participant self-reported data that was identified as having data quality issues was documented but ultimately, no revisions were made to the data collected in the web-based survey given the nature of self-reported survey data. Any data quality issues identified with ODT results were resolved with Millenium Health prior to database lock.

Survey data analysis

Statistical analyses of all objectives using survey data was conducted by statisticians from the DCC. A detailed statistical analysis plan for the primary objective and all secondary objectives that required quantitative analyses was drafted prior to database lock and finalized prior to dissemination of results to the study team. Due to the nature of the exploratory objectives, a statistical analysis plan for these objectives that required quantitative analyses was drafted after database lock. The analysis population for each objective was selected based on the completion of the baseline survey, weekly surveys, drug use during the observation period, FTS use during the observation period, and receipt of ODT results (see Table 1). Cross-sectional outcomes were analyzed using a generalized linear model with an appropriate distribution and link function and fixed effects included the exposure of interest as well as a set of pre-specified baseline covariates. Outcomes measured repeatedly over time were analyzed using a GEE approach with an appropriate distribution and link function and fixed effects included the exposure of interest, a set of pre-specified baseline covariates, as well as a set of time-varying covariates. Any missing data was assumed to be missing completely at random, with the caveat that multiple imputation be used if the percentage of participants not included in the primary analysis of each objective due to missing data was greater than 5%. All hypotheses were tested using a two-sided significance level of 0.05. No adjustment was made for multiple comparisons across outcomes or analyses within a specific objective and so all p-values presented are purely descriptive in nature.

Qualitative data analysis

The DCC contracted a professional transcriptionist to transcribe all interviews. The qualitative team, led by the DCC and staffed with representatives from each state team, used NVivo Plus 12 for Windows [42] to develop two codebooks (one for each population). Study staff were responsible for coding interview transcripts and analyzing findings from their own state.

Enrollment and data collection have been completed and data analysis is underway. Study findings will be presented in subsequent publications. From May-December 2023, the study screened 1,405 individuals and enrolled 1,156 PWUD (82.3% of screened individuals) (Figure 1). The full sample, consisting of enrolled participants who completed the baseline survey and at least two of four weekly surveys and reported drug use at least once during the 28-day observation period, was 732 PWUD (63.3% percent of enrolled participants). A total of 309 PWUD completed an ODT, of which n=269 were used for the ODT analysis, and 120 PWUD completed one-on-one interviews.

The study achieved 97.6% (732/750) of its enrolled target for PWUD participants. It accomplished 100% of the study target of 120 interviews with the PWUD sample. There were more weekly surveys completed in Weeks 2, 3, and 4 of the 28-day observation period compared to Week 1, even with participant withdrawals (Figure 1). From the secondary population of 36 harm reduction organizations, employees of 28 (77.8%) in 22 counties across 3 states completed the survey and employees of 24 (66.7%) completed the interview. The study began with fourteen partner organizations that hosted data collection and ended with seven (see Discussion and Table 4). Study findings will be presented in subsequent publications.

To our knowledge, few researchers have provided methodological reflections on protocol implementation for harm reduction studies and none for FTS studies. To encourage researchers to develop large-sample and multi-state FTS study designs that engage community partner organizations, and to provide insight into implementation, we discuss factors that contributed to implementation success along with areas in which we encountered complexity [27].

Several factors supported successful implementation of this three-state study protocol. An overarching factor was the ability to tailor staffing models and data collection approaches to accommodate the unique conditions at each data collection site.

Another factor was the support of the HCS. Currently in its sixth year, the HCS provided the Stay Safe Study with local community expertise, access to established partnerships, and processes to facilitate study operations and implementation [28, 43-45]. HCS staff have substantial experience implementing a large community-engaged study and supported teams in identifying potential partner organizations, helping with recruitment of study staff, and making purchasing requests. A related benefit of HCS association was that organizations that are members of community coalitions participating in the HCS were receptive to hosting data collection as partner organizations or joining this ancillary study as organizational participants.

Factors unrelated to operational support from the HCS were associated with successful implementation. In line with best practices for conducting research with PWUD [46, 47], the study team selected appropriate incentive amounts for PWUD for each data collection event and set an increasing weekly survey incentive rate (by $5 each week) during the 28-day observation period to encourage retention (Table 2). The DCC hosted centralized survey data collection which facilitated troubleshooting for server and login problems. This approach also eliminated the need for state teams to host their own survey data collection. The DCC hosted a study SmartSheet (smartsheet.com) for all study staff to post implementation challenges on the day they arose. This central forum allowed teams to suggest resolutions, make recommendations to the DCC on data collection operations, which were quickly implemented, and learn from each team’s experience.

Protocol development and implementation, which spanned over two years, was complex and included diverse approaches to solving challenge encounters. We illustrate lessons learned with examples for four implementation areas. In Table 4, we provide recommendations to researchers.

Conducting research in communities. Partner organizations operate direct service provision sites that provide harm reduction services to a diverse clientele. They juggle many demands throughout the day in tight spaces and with a small number of staff. Sites were frequently crowded with little room for teams to work. At times, data collection conflicted with their operations. As a result, some partner organizations asked teams to move their data collection onto adjacent sidewalks or parking lots. However, outdoor data collection created unpredictability and instability by exposing study staff and PWUD participants to weather hazards [27]. One partner organization asked a team to end data collection because noise from participants and long lines outside business offices interrupted meetings and phone calls. Study staff who travelled with mobile vans that provided harm reduction services to neighborhoods had less opportunity to offer privacy to PWUD inside the vehicles, which limited enrollment and data completion. One team ended data collection at a site because the team lead felt they could not guarantee the safety of study staff.

Making timely payments. During the first week of data collection, PWUD participants in one state attempted to activate their electronic payment cards using personal identifiers that were not registered to the cards. Participants experienced a high level of distress when they could not retrieve their payments and sent a large volume of phone calls, voice mails, and email messages to the team. Some participants showed in person at data collection sites with high levels of distress after being unable to retrieve their payments, which increased the work of study staff and impacted data collection for other participants. The team resolved this by distributing an approved activation handout for PWUD participants.

Oversight of study staff. In one state, employees of direct service provision sites who were contracted to collect PWUD data did not consistently follow data collection practices for the ODT, which then required additional IRB review. In another state, two study staff members drove 40 hours per week to six data collection sites and worked an additional 30 hours per week to meet high demand for study enrollment. To allow staff time to rest and meet demand for participant, the team halted recruitment for two months and resumed data collection with just two sites.

Returning ODT results. The study team agreed to return ODT results to PWUD participants to provide potentially actionable information to participants about their supply. Medical directors for all teams reviewed and approved the oral consent process and form, and the oral fluid collection procedures. Two states delivered ODT results to PWUD participants using either telephone calls or a combination of telephone calls and in-person delivery at data collection sites. One state hand-delivered all ODT results in a sealed envelope to PWUD participants at data collection sites. While this approach increased the team’s confidence in protecting participants’ privacy, it was burdensome to participants, with few showing to receive their ODT results.

Strengths and limitations of the study

A key strength of this prospective cohort design study was the use of a multi-state design and the recruitment of 14 partner organizations hosting data collection. This approach generated both diversity of PWUD participants and the largest sample to date of PWUD participants in a FTS study. State teams implemented a common protocol which optimized feasibility and study rigor, although it resulted in different engagement and retention rates in each state. Additional strengths included the use of weekly surveys during the 28-day observation period to investigate daily patterns of drug and FTS use by PWUD participants, use of an oral fluid drug test to check concordance and discordance of self-reported substance use by PWUD participants, and the inclusion of harm reduction organization participants as a secondary population to build the limited evidence base on organizational barriers and facilitators to FTS distribution.

There are several limitations of the Stay Safe Study design and implementation. Survey and interview data collected from PWUD were self-report, which limits validity and reproducibility. To protect the privacy of PWUD participants and foster trust, the study did not require PWUD participants to provide photo identification at enrollment. This decision led to a small number of duplicate enrollments. Where possible, the DCC identified each of these from identical contact information and removed duplicate enrollments from the data set. Partner organizations that hosted PWUD data collection activities and organizational participants were recruited opportunistically and were not a representative sample from the three states. All partner organizations hosting data collection sites were required to distribute FTS as an inclusion criterion, which may have overrepresented FTS use and/or rates of FTS acceptability in the enrolled PWUD sample. Eleven data collection sites were located in metropolitan areas according to rural-urban commuting codes, which resulted in a highly urban sample of PWUD participants. Populations at significant risk of fentanyl-related overdose, such as non-Hispanic/Black stimulant users and youth who use substances recreationally may be underrepresented in our PWUD enrolled and full samples.

[Insert Table 4 here]

To our knowledge, this is the first multi-state study investigating FTS use and distribution. The study team successfully enrolled a large sample of PWUD and organizational participants, followed a cohort of PWUD for 28 days, and generated rich data using three types of instruments. A key lesson learned is that in a multi-state study with two populations, the desire for harmonized approaches to data collection must be balanced with the need of teams to tailor protocol implementation to data collection sites in their states. Each team makes the best decisions for their circumstances and there is often no single correct approach. As we saw with this study, teams must be prepared to rapidly pivot when challenges arise. Relationships of trust between teams, partner organizations, and participants ultimately drive and shape implementation success.

DCC Data coordinating center

FTS: Fentanyl test strips

HCS: HEALing Communities Study

IRB Institutional Review Board

KY: Kentucky

NIDA National Institute on Drug Abuse

NIH National Institutes of Health

NY: New York

ODT: Oral fluid drug test

OH: Ohio

ORRB: Overdose risk reduction behavior

PWUD: People who use drugs

Availability of instruments

Consideration will be given to sharing the instruments upon request. Such requests should be sent to the corresponding author.

Ethics approval and consent to participate

The study was approved by Advarra (Pro00068304) on March 16, 2023, with additional approval by Columbia University IRB (iIRB-AAAU5847) on August 29, 2023.

Consent for publication

Not applicable.

Competing interests

Amanda Fallin-Bennett is the co-founder of Voices of Hope (Kentucky), a partner organization in the Stay Safe Study.

Funding

This research was supported by the National Institutes of Health and the Substance Abuse and Mental Health Services Administration through the NIH HEAL (Helping to End Addiction Long-term®) Initiative under award numbers UM1DA049394, UM1DA049406, UM1DA049415, UM1DA049417. Drs. Villani and Chandler were substantially involved in UM1DA049394, UM1DA049406, UM1DA049415, and UM1DA049417, consistent with their roles as Scientific Officers. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health, the Substance Abuse and Mental Health Services Administration, or the NIH HEAL Initiative®.

The HEALing Communities Study protocol (Pro00038088) and the Stay Safe Study protocol (Pro0006830) were approved by Advarra Inc., the HEALing Communities Study single Institutional Review Board.

We wish to acknowledge the participation of the HEALing Communities Study communities, community coalitions, community harm reduction agencies, Community Advisory Boards, and state government officials who partnered with us on this study.

Authors' contributions

D.C.B., R.C., R.K.C., J.E.C., J.L.D., M.E.D., N.E-B., A.F-B., L.C.F., S.F., B.F., K.G., L.G., M.E.H., M.H., R.D.J., M.K., B.S.L., K.M., E.O., C.R., R.V-S., J.V., and S.L.W. developed the study concept and design.

J.E.C., J.L.D., N.E-B., S.F., K.G., L.G., R.D.J., K.E.L., B.S.L., K.M., E.O., C.R., R.V-S., and S.L.W. obtained funding.

J.E.C., M.E.D., A.F-B., K.G., B.S.L., M.R., and R.V-S. performed data collection.

D.C.B., M.E.H. E.O., and M.R. were responsible for data management.

D.C.B. and M.E.H. performed statistical analysis.

D.C.B., J.E.C., and M.E.D. prepared the figure.

D.C.B., R.K.C., J.E.C., M.E.D., N.E-B., K.G., E.O., and R.V-S. drafted the manuscript.

All authors critically revised the manuscript for review.

Acknowledgements

We are grateful to the partner organizations and staff that hosted research activities for this study, the individuals who attended service sites for their interest and commitment to this study, and the harm reduction organizations that informed our understanding of FTS distribution. We would also like to thank staff of the three state HCS teams, who provided invaluable operational support and guidance.

We wish to acknowledge the contributions of Dr. Rebecca D. Jackson (deceased), who led the HEALing Communities Study and was instrumental in conceptualizing and obtaining funding for the Stay Safe Study. As she said, “We have a moral imperative to address the opioid crisis.” Dr. Jackson was a visionary, leader, and mentor to many, and she continues to have impact.

Athey A, Kilmer B, Cerel J. An overlooked emergency: more than one in eight US Adults have Hhad their lives disrupted by drug overdose deaths. Am J Public Health. 2024;114(3):276–9.
The U.S. Centers for Disease Control and Prevention. CDC Wonder. 2024. https://wonder.cdc.gov/. Accessed July 15, 2024.
U.S. Overdose Deaths In 2021 Increased Half as Much as in 2020 – But Are Still Up 15%. 2022. https://www.cdc.gov/nchs/pressroom/nchs_press_releases/2022/202205.htm. Accessed June 14, 2024.
U.S. Overdose Deaths Decrease in 2023, First Time Since 2018. 2024. https://www.cdc.gov/nchs/pressroom/nchs_press_releases/2024/20240515.htm#print. Accessed June 14, 2024.
Wagner KD, Fiuty P, Page K, Tracy EC, Nocera M, Miller CW, et al. Prevalence of fentanyl in methamphetamine and cocaine samples collected by community-based drug checking services. Drug Alcohol Depend. 2023;252:110985.
Palamar JJ. Awareness that cocaine can contain fentanyl among nightclub and festival attendees in New York City, 2018–2022. Public Health Nurs. 2023;40(4):566–71.
Palamar JJ, Fitzgerald ND, Keyes KM, Cottler LB. Drug checking at dance festivals: a review with recommendations to increase generalizability of findings. Exp Clin Psychopharmacol. 2021;29(3):229–35.
Peiper NC, Clarke SD, Vincent LB, Ciccarone D, Kral AH, Zibbell JE. Fentanyl test strips as an opioid overdose prevention strategy: findings from a syringe services program in the Southeastern United States. Int J Drug Policy. 2019;63:122–8.
Oh H, Kim K, Miller D, Veloso D, Lin J, McFarland W. Fentanyl self-testing in a community-based sample of people who inject drugs, San Francisco. Int J Drug Policy. 2020;82:102787.
Tilhou AS, Zaborek J, Baltes A, Salisbury-Afshar E, Malicki J, Brown R. Association of fentanyl test strip use, perceived overdose risk, and naloxone possession among people who use drugs. Subst Use Misuse. 2024;59(2):254–7.
Weicker NP, Owczarzak J, Urquhart G, Park JN, Rouhani S, Ling R, et al. Agency in the fentanyl era: exploring the utility of fentanyl test strips in an opaque drug market. Int J Drug Policy. 2020;84:102900.
Park JN, Frankel S, Morris M, Dieni O, Fahey-Morrison L, Luta M, et al. Evaluation of fentanyl test strip distribution in two Mid-Atlantic syringe services programs. Int J Drug Policy. 2021;94:103196.
Kutscher E, Barber Grossi M, LaPolla F, Lee JD. Fentanyl test strips for harm reduction: a scoping review. J Addict Med. 2024. 10.1097/ADM.0000000000001321.
Tilhou AS, Zaborek J, Baltes A, Salisbury-Afshar E, Malicki J, Brown R. Differences in drug use behaviors that impact overdose risk among individuals who do and do not use fentanyl test strips for drug checking. Harm Reduct J. 2023;20(1):41.
Reed MK, Guth A, Salcedo VJ, Hom JK, Rising KL. You can't go wrong being safe: Motivations, patterns, and context surrounding use of fentanyl test strips for heroin and other drugs. Int J Drug Policy. 2022;103:103643.
Reed MK, Roth AM, Tabb LP, Groves AK, Lankenau SE. I probably got a minute: Perceptions of fentanyl test strip use among people who use stimulants. Int J Drug Policy. 2021;92:103147.
Reed MK, Salcedo VJ, Guth A, Rising KL. If I had them, I would use them every time: perspectives on fentanyl test strip use from people who use drugs. J Subst Abuse Treat. 2022;140:108790.
Goldman JE, Krieger MS, Buxton JA, Lysyshyn M, Sherman SG, Green TC, et al. Suspected involvement of fentanyl in prior overdoses and engagement in harm reduction practices among young adults who use drugs. Subst Abus. 2019;40(4):519–26.
Goldman JE, Waye KM, Periera KA, Krieger MS, Yedinak JL, Marshall BDL. Perspectives on rapid fentanyl test strips as a harm reduction practice among young adults who use drugs: a qualitative study. Harm Reduct J. 2019;16(1):3.
Krieger MS, Goedel WC, Buxton JA, Lysyshyn M, Bernstein E, Sherman SG, et al. Use of rapid fentanyl test strips among young adults who use drugs. Int J Drug Policy. 2018;61:52–8.
Zibbell JE, Peiper NC, Clarke SED, Salazar ZR, Vincent LB, Kral AH, et al. Consumer discernment of fentanyl in illicit opioids confirmed by fentanyl test strips: lessons from a syringe services program in North Carolina. Int J Drug Policy. 2021;93:103128.
Bailey K, Abramovitz D, Artamonova I, Davidson P, Stamos-Buesig T, Vera CF, et al. Drug checking in the fentanyl era: utilization and interest among people who inject drugs in San Diego, California. Int J Drug Policy. 2023;118:104086.
Park JN, Tomko C, Silberzahn BE, Haney K, Marshall BDL, Sherman SG. A fentanyl test strip intervention to reduce overdose risk among female sex workers who use drugs in Baltimore: results from a pilot study. Addict Behav. 2020;110:106529.
Watson DP, Ray B, Phalen P, Duhart Clarke SE, Taylor L, Swartz J, et al. Fentanyl exposure and detection strategies utilized by clinical trial participants seeking linkage to opioid use disorder treatment at a syringe service program. J Med Toxicol. 2024;20(1):13–21.
Gunn CM, Maschke A, Harris M, Schoenberger SF, Sampath S, Walley AY, et al. Age-based preferences for risk communication in the fentanyl era: ‘a lot of people keep seeing other people die and that's not enough for them’. Addiction. 2021;116(6):1495–504.
Volkow ND, Califf RM, Sokolowska M, Tabak LA, Compton WM. Testing for fentanyl - urgent need for practice-relevant and public health research. N Engl J Med. 2023;388(24):2214–7.
Bazzi AR, Harvey-Vera A, Buesig-Stamos T, Abramovitz D, Vera CF, Artamonova I, et al. Study protocol for a pilot randomized controlled trial to increase COVID-19 testing and vaccination among people who inject drugs in San Diego County. Addict Sci Clin Pract. 2022;17(1):48.
Walsh SL, El-Bassel N, Jackson RD, Samet JH, Aggarwal M, Aldridge AP, et al. The HEALing (Helping to End Addiction Long-term®) Communities Study: protocol for a cluster randomized trial at the community level to reduce opioid overdose deaths through implementation of an integrated set of evidence-based practices. Drug Alcohol Depend. 2020;217:108335.
Federal Grantees May Now Use Funds to Purchase Fentanyl Test Strips. 2021. https://www.samhsa.gov/newsroom/press-announcements/202104070200. Accessed June 14, 2024.
Davis CS, Lieberman AJ, O'Kelley-Bangsberg M. Legality of drug checking equipment in the United States: a systematic legal analysis. Drug Alcohol Depend. 2022;234:109425.
McKnight C, Des Jarlais DC. Being hooked up during a sharp increase in the availability of illicitly manufactured fentanyl: adaptations of drug using practices among people who use drugs (PWUD) in New York City. Int J Drug Policy. 2018;60:82–8.
Rouhani S, Park JN, Morales KB, Green TC, Sherman SG. Harm reduction measures employed by people using opioids with suspected fentanyl exposure in Boston, Baltimore, and Providence. Harm Reduct J. 2019;16(1):39.
Foglia R, Kline A, Cooperman NA. New and emerging opioid overdose risk factors. Curr Addict Rep. 2021;8(2):319–29.
Stein MD, Kenney SR, Anderson BJ, Bailey GL. Perceptions about fentanyl-adulterated heroin and overdose risk reduction behaviors among persons seeking treatment for heroin use. J Subst Abuse Treat. 2019;104:144–7.
Mars SG, Ondocsin J, Ciccarone D. Toots, tastes and tester shots: user accounts of drug sampling methods for gauging heroin potency. Harm Reduct J. 2018;15(1):26.
Drug Policy Alliance. Recommendations for Community Driven Drug Policy Research. 2023. https://drugpolicy.org/wp-content/uploads/2023/05/Recommendations_for_Community_Driven_Research.pdf. Accessed June 14, 2024.
The US. Department of Agriculture. What is Rural? 2024. https://www.ers.usda.gov/topics/rural-economy-population/rural-classifications/what-is-rural/. Accessed May 30, 2024.
Buer L-M. Good Practices and Ethical Data Collection at Harm Reduction Programs: A Brief Summary. 2023. https://harmreductionhelp.cdc.gov/s/article/Good-Practices-and-Ethical-Data-Collection-at-Harm-Reduction-Programs-A-Brief-Summary. Accessed June 14, 2024.
Lewis NM, Smeltzer RP, Baker TJ, Sahovey AC, Baez J, Hensel E, et al. Feasibility of paying people who use drugs cash to distribute naloxone within their networks. Harm Reduct J. 2024;21(1):42.
Austin T, Lavalley J, Parusel S, Collins AB, Olding M, Boyd J. Women who use drugs: engagement in practices of harm reduction care. Harm Reduct J. 2023;20(1).
Friedman JR, Nguemeni Tiako MJ, Hansen H. Understanding and addressing widening racial inequalities in drug overdose. Am J Psychiatry. 2024;181(5):381–90.
Lumivero LLC, Plus V. Version 12.1. https://www.lumivero.com/nvivo. Accessed June 14, 2024.
El-Bassel N, Jackson RD, Samet J, Walsh SL. Introduction to the special issue on the HEALing Communities Study. Drug Alcohol Depend. 2020;217:108327.
Sprague Martinez L, Rapkin BD, Young A, Freisthler B, Glasgow L, Hunt T, et al. Community engagement to implement evidence-based practices in the HEALing communities study. Drug Alcohol Depend. 2020;217:108326.
Young AM, Brown JL, Hunt T, Sprague Martinez LS, Chandler R, Oga E et al. Protocol for community-driven selection of strategies to implement evidence-based practices to reduce opioid overdoses in the HEALing Communities Study: a trial to evaluate a community-engaged intervention in Kentucky, Massachusetts, New York and Ohio. BMJ Open. 2022;12(9):e059328.
Canadian Centre on Substance Abuse and Addiction. Guidelines for Partnering with People with Lived and Living Experience of Substance Use and Their Families and Friends. 2021. https://www.ccsa.ca/sites/default/files/2021-04/CCSA-Partnering-with-People-Lived-Living-Experience-Substance-Use-Guide-en.pdf. Accessed June 14, 2024.
Langness M et al. Equitable Compensation for Community Engagement Guidebook. 2023. https://www.urban.org/research/publication/equitable-compensation-community-engagement-guidebook. Accessed June 14, 2024.

Tables 1 to 4 are available in the Supplementary Files section.

Competing interest reported. Amanda Fallin-Bennett is the co-founder of Voices of Hope, a Kentucky partner organization in the Stay Safe Study.

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Prospective Cohort Study of Fentanyl Test Strip Use and Distribution in Three States: The Stay Safe Study Protocol and Implementation Recommendations for Researchers

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Abstract

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Background

Methods

Study structure and development

Definition of terms

Study rationale

Populations and instruments

Objectives and outcomes

Sample, setting, and procedures

Team staffing models

Partner organizations

PWUD participants

Inclusion criteria

Incentive payments.

Study advertising and setting

Estimating recruitment targets

PWUD data collection

Screener, baseline, and weekly surveys

Oral fluid drug test (ODT)

Interview

Organization participants

Sample and setting

Inclusion criteria

Incentive payments

Organization data collection

Survey

Interview

Educational materials

Sample Size, Data Monitoring, and Analysis

Sample size

Data monitoring

Survey data analysis

Qualitative data analysis

Results

Discussion

Strengths and limitations of the study

Conclusions

Abbreviations

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