by Eric Morse, MD; Graeme Christianson, BSE; Melissa Olivadoti, PhD; and John Timberlake, MBA 

Dr. Morse is with Carolina Performance in Raleigh, North Carolina and Morse Clinics in Raleigh, North Carolina. Mr. Christianson is with 4C Research Group in Somerton, United Kingdom. Dr. Olivadoti is with Assisi Medical Affairs Consulting, LLC in Henderson, Nevada. Mr. Timberlake is with Berkshire Biomedical Corporation in Dallas, Texas.

Funding: The study was funded by Berkshire Biomedical Corporation.

Disclosures: EM is a paid advisor of Berkshire Biomedical Corporation. GC is paid employee and holds stock with 4C Research Group. MO is a paid consultant of Berkshire Biomedical Corporation. JT is an employee of Berkshire Biomedical Corporation and holds equity in the company.

Innov Clin Neurosci. 2024;21(10–12):25–33.

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Abstract

Background: Methadone is commonly utilized to treat opioid use disorder (OUD). Requirements to visit an opioid treatment provider (OTP) clinic for methadone treatment limits access to treatment, impacts quality of life, and reduces OUD treatment program retention. The Computerized Oral Prescription Administration (COPA) system is a dual-biometric dispensing device for take-home dosing that could reduce the impacts of methadone administration on patients and clinic staff.

Objective: To identify challenges for patients treated with methadone for OUD and gain their perspectives on COPA.

Methods: Adult patients treated with methadone at a single-site OTP clinic were recruited to complete a qualitative interview regarding their experience with methadone and the impact that expansion of take-home doses would have on their life. Participants were provided printed resources describing COPA and handled a COPA device before being asked for their perspectives.

Results: Participants (n=12) were 58.33 percent male and 41.67 percent female, and had no take-home doses (n=5), 2 to 5 days of take-home doses (n=4), or six or more days of take-home doses (n=3). Most (91.67%) participants desired more take-home doses, and 66.7 percent stated more take-home doses would reduce the negative impact of OUD treatment on their ability to work. Average time and cost per trip to obtain their methadone dose at the clinic was 75 minutes and $36.58, respectively. Participants responded positively toward COPA. Participants with no take-home privileges would pay $126.88 per month to obtain take-home privileges by using COPA, and those with take-home privileges would pay $30.31 per month to keep the same level of take-home doses and $117.50 per month to expand their take-home doses using COPA.

Conclusion: Participants endured a monetary and time burden to access their methadone treatment, and wished to have more take-home doses to reduce the frequency of their visits to the OTP clinic. Participants viewed take-home doses as having a positive impact on their ability to care for family members, hold a job, and travel, and they appreciated the key attributes of COPA and were willing to invest their own funds to gain access to the device. COPA is a potential solution to expand take-home methadone access to patients while ensuring safety, adherence, retention, and appropriate use. 

Keywords: Methadone, take-home dose, opioid use disorder, opioid treatment program

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Opioid use disorder (OUD) is a pervasive condition that significantly diminishes quality of life.¹ It is defined as a chronic use of opioids that causes significant clinical distress or impairment. The disorder can range from dependence to addiction.² It is estimated that 2.7 million people in the United States (US) have had OUD in the past 12 months, and it was predicted that 109,940 Americans died from drug overdose in the 12 months ending in January 2020.³ Furthermore, reductions in opioid prescriptions have not led to reductions in drug-related mortality,⁴ making treatment options a crucial solution to a long-term challenge.

Opioid use has been documented to change neural function through tolerance and dependence in specific areas of the brain, including the ventral tegmental area, nucleus accumbens, and locus ceruleus. These changes require appropriate treatments to halt cravings and reduce or abate symptoms of withdrawal to prevent future use.⁵ 

Methadone is a synthetic, long-term opioid agonist medication that is approved by the US Food and Drug Administration (FDA) for the management and treatment of OUD.⁶ Methadone therapy for OUD produces minimal tolerance and alleviates cravings and compulsive drug use.⁵ It is also able to normalize many aspects of the hormonal disruptions found in individuals with opioid addiction,^7–9 which can moderate the exaggerated cortisol stress response that increases the potential of relapse in stressful situations. Methadone for OUD treatment has also been shown to lower overdose rates by 76 percent and opioid-related emergency room (ER) visits by 32 percent.¹⁰ Consistent evidence supports that treatment with methadone lowers risk of death and criminal acts and improves physical and social functioning of those with OUD.^11–14 Yet, despite the widespread problem of OUD and consensus that methadone is an efficacious treatment, only approximately 550,000 people in the US receive methadone to treat OUD.¹⁵

Multiple barriers exist in ensuring appropriate treatment of OUD with methadone. Regulations have led to severe shortages in availability and an underutilization of methadone despite a worsening overdose crisis.¹⁶ By law, methadone is only accessible from federally certified opioid treatment provider (OTP) clinics, which are limited in number and geography.¹⁷ There is a lack of available centers and qualified staff to support this treatment, especially in rural areas, with most patients having to come to the clinic daily.^16,18,19 Many clinics have limited hours of operation and are typically only open during the early morning hours, which can impact patient ability to maintain their treatment along with balancing responsibilities and daily activities, such as work and familial obligations, or cause a patient to miss their dosing opportunity if they are unable to attend during the prescribed hours. Limited hours can also reduce the possibility of twice-daily dosing (split-dosing) for those who might benefit, including pregnant patients or those who metabolize methadone more quickly.^20,21 The true extent of the number of patients who would benefit from twice-daily dosing is also not fully known, as testing for drug metabolism is not common practice, and there are no evidence-based recommendations or research trials evaluating the benefit of split-dosing, especially given the higher dosages of methadone required due to the wide use of fentanyl.²²

Attending an OTP clinic for methadone treatment can elicit negative impacts on psychological wellbeing. This is often due to patient feelings of reduced freedom and low dignity, as well as feeling as though they are being treated as addicts or criminals due to restrictions on methadone administration.¹⁶ Requirements of attending a clinic to receive medications for OUD (MOUD) can also be difficult for those who are trying to maintain steady employment, attend school, or manage their daily lives.²³ Missing a dose of methadone results in significant consequences, including opioid withdrawal syndrome and risk of relapse,²⁴ making consistent use of the medication crucial to patient success. 

Take-home dose privileges for methadone have been a useful tool for treatment of OUD. A mixed-methods study demonstrated that take-home dose flexibility among stable patients was associated with receiving more take-home doses, higher rates of treatment retention, and lower rates of opioid-positive drug tests,²⁵ demonstrating the ability of take-home doses to help patients maintain their sobriety and stay on treatment. However, limitations on or disallowance of take-home doses are a deterrent to initiating methadone treatment.^26,27 Without proper adherence to daily prescribed doses of methadone, patients have an increased risk of relapse and overdose,²³ making access and ease of use of methadone an unmet need of high concern.

Guidelines for take-home use of methadone for OUD were relaxed by the Substance Abuse and Mental Health Services Administration (SAMHSA) during the COVID-19 pandemic, allowing for expanded use of take-home doses based on the clinical judgement of the OTP personnel. These regulations proved to be largely useful and cost-effective²⁸ but were later rescinded by many clinics once the pandemic was no longer emergent.²⁹ Revised guidelines by SAMHSA and the Department of Health and Human Services (HHS) for OTP regulations were released in February 2024 that made take-home medication flexibilities granted during the COVID-19 pandemic permanent.³⁰ However, the application of these guidelines is largely left to the discretion of the OTP clinics and staff. Qualifications for take-home privileges and availability of take-home doses vary widely by state, clinic, and provider and can result in added restrictions, burdens, and challenges to treatment for patients beyond the federal guidelines and large differences between OTP practices. Each state must determine if they will revise their own take-home guidelines to be consistent with the SAMHSA 2024 guidance or remain more restrictive. 

Despite the benefits of take-home doses, a combination of restrictions, requirements, negative attitudes, and differences in decisions by clinics limits the use of take-home doses. Some healthcare providers (HCPs) might be skeptical of the safety of the practice due to concerns that take-home doses might increase risk of abuse, or that diversion might limit use,^31,32 despite studies showing that the odds of these instances are low.³³ This misunderstanding on the risks of take-home methadone has resulted in the strict requirements for granting patients take-home privileges, even after the relaxation of federal guidelines. 

When granting take-home doses, security must be maintained to reduce diversion of doses. This is attempted through lockboxes or locked pillboxes, but current take-home methods do not allow for the clinic to know whether the patient took more than one dose in a day, if they diverted their dose, or if they took less than the full dose and diverted the remaining dose, leaving an unmet need for communication on these items.

For liquid methadone, patients are required to manage a bottle for each dose they take home, and clinics have requirements for returning their bottles for bottle checks by returning to the clinic on demand. If bottles are not fully accounted for or the patient is not able to come in at the requested time, they risk losing their take-home privileges,²³ and studies have shown that patients are more likely to discontinue methadone treatment when take-home doses are removed from treatment.^26,27 These requirements can also make it difficult for patients to have a flexible schedule, travel, or be away from home²³ or require them to arrange dosing at their travel location. 

An option for methadone take-home treatment that allows for patient privacy in taking medications, as well as convenience, safety, and monitoring of adherence is a crucial unmet need. New solutions are needed to ensure that the correct dose is received by the patient (intended user) at the time indicated by the provider, reduce intentional or accidental misuse of methadone, reduce chances of diversion, validate medication adherence, increase provider-patient communication, improve the ability for patients to have take-home privileges, and reduce time spent commuting to and being in the clinic for dosing or refilling of take-home doses. 

The Computerized Oral Prescription Administration (COPA^TM) device and system are a potential solution to meet these needs through a variety of measures. The COPA device is a handheld, automated, personalized, oral liquid dispensing system designed to deliver liquid oral medications during a specified time window to only the Authenticated Intended User (AIU^TM, the patient) upon confirmation of dual biometric confirmation (fingerprint and dentition) at each dose. It is currently under development and is not yet approved by the FDA or commercially available. 

The objective of the COPA system is to act as an aid to medical providers in managing therapeutic regimens for patients, including the delivery and remote management of oral liquid methadone for MOUD. The system allows for remote monitoring and patient adherence assistance through its communication capabilities, including sending real-time dosing reminders by text and/or email to the patient or other individuals (their loved one[s], HCP, or OTP clinic), alerts for when the dose is due or completed, and alerts for when the next dose is scheduled. It also tracks and communicates noncompliant use attempts and missed doses to HCPs and/or clinic staff via an encrypted and Health Insurance Portability and Accountability Act (HIPAA)-secure database. The device provides remote monitoring via cellular transmission capability and operates via a rechargeable battery, allowing for flexibility in where it is used and stored. A standard 30mL (1oz) or 60mL (2oz) pharmacy medication bottle is filled with the medication and secured with a tamperproof smart bottle cap (SynCap^TM), which is a single-use, disposable, locking medication bottle cap that is linked to a specific COPA device. The COPA SynCap contains the specific patient’s dosing information. An individual COPA device is linked to the patient at setup, when the patient’s fingerprints and dentition imprint (light mouth bite on the mouthpiece) are saved with the device. The device receives the dosage volume, time range of dispensation, and number of doses per day (with multiple doses being an option for the prescriber) via the SynCap. This ensures that the correct dose of medication is only dispensed to the AIU at the correct time(s) through these linked items (COPA device and SynCap). Changes in biometrics (i.e., if there is a change in patient’s dentition characteristics, such as tooth replacement or dentures) require resetting the device’s settings for the patient. The COPA system is designed to interface with the clinic methadone dosing software.

Despite the capabilities of the COPA system, the receptivity among patients in a MOUD program at an OTP clinic, along with potential life impacts due to using the COPA, are unknown. A survey study was undertaken with patients currently receiving methadone as part of their OUD treatment to 1) identify the current processes, pain points, and challenges among patients taking methadone as part of a medication-assisted treatment program at an OTP clinic, including patients with and without take-home privileges; 2) identify the perceived key benefits, advantages, concerns, and drawbacks associated with the COPA device and system; and 3) capture receptivity among patients of using COPA to enable either new or extended take-home privileges.

Methods

Ethics. Participants signed consent forms that allowed the sharing of de-identified interview responses and demographic information with the company, as well as in educational uses, including publications. Participants were masked to the sponsoring organization prior to the interview. All information was de-identified of personal information when data was shared with the sponsor so that participants could not be identified by their responses. Research was done in concordance with the Declaration of Helsinki (2013). 

Clinic and survey setting. The setting for the survey included a single site OTP clinic in North Carolina, US, with normal dosing hours of 5:30 to 11 am Eastern Standard Time, Monday through Friday and 7 to 9 am on Saturdays and Sundays. The clinic allowed take-home doses of liquid methadone on Sunday to almost all patients on a stable dose of methadone. A higher number of take-home doses were granted by the OTP personnel to patients dependent on 30 days of illicit-free urine drug screens. Expanded take-home dose privileges started at two days of take-home, and increased by one day with each month of illicit-free drug screens to a maximum of six days. Patients were able to apply for exceptions for more take-home doses with their treatment team in specific circumstances. Methadone take-home doses were stored in bottles (with 1 bottle for each daily dose) and were required to be kept in a patient’s lockbox. Patients were responsible for the safety and security of their bottles, and the clinic did not replace lost, stolen, broken, or spilled bottles. Patients with take-home doses were required to bring in their empty bottles for inspection at each clinic visit to maintain their take-home dose status.

Participant selection. Participants who were 18 years of age or older and using liquid methadone for treatment at the OTP clinic were eligible for the study. Participants were required to have been treated at the clinic for at least two weeks, not missed more than two in-clinic appointments for dosing over the last month, and been willing to participate in a 45 to 60 minute in-person, one-on-one interview at the clinic. 

Recruitment was done via posters placed in the clinic advertising confidential paid interviews to share feedback about take-home methadone and a medical device, and clinic patients who were interested in the study were requested to fill out a form that covered the screening criteria to be considered for inclusion. The target recruitment was a total of 12 participants and aimed to include a roughly equal representation of participants (n=2–5 participants per group) who did not have expanded take-home privileges other than potentially the normal Sunday dose (referred to as “no take-home”), those who had 2 to 5 days of take-home doses total, and those who had six or more days of take-home doses total. Participants were compensated $75 for their time after completing the interview.

Questions. During the interview, background information was collected, including ethnicity and sex. Information on treatment experience, including duration of taking methadone, number of times per day they take methadone, cost for transportation to the clinic, willingness/interest in splitting the dose of methadone to increase take-home privileges, duration of methadone use before receiving take-home doses, how many take-home doses per week they receive (if applicable), clarity of requirements for take-home privileges prior to receiving doses, beliefs about take-home dose requirements, interest in receiving take-home doses/receiving more days of take-home doses and reasons for their answer, and current or potential storage location of take-home doses, was also collected. For those receiving no take-home doses, questions also focused on the impact of coming into the clinic every day and the potential impact of take-home doses on their lives. For those receiving take-home doses, questions focused on the impact of coming into the clinic for doses, the benefits and challenges of having take-home doses, and the logistics around accounting for and managing take-home doses.

Questions about the impact of dosing and clinic visits included duration (time in minutes) from leaving home to receiving a dose at the clinic and returning home or going to work, duration (time in minutes) spent on transportation to/from the clinic, the type of transportation used (car, bus, other), estimate of costs to get to/from the clinic (including gas or payment for transportation), impact of having to come into the clinic on daily life, and the potential impact of reducing the number of times coming to the clinic through use of take-home doses. 

Questions were then asked about key attributes of the COPA. Prior to being asked questions about the COPA system, participants were provided with two printed slides with information about the COPA System (Figures 1 and 2), were shown a 35-second animated demonstration video (https://www.berkshirebiomedical.com/index), and were given an actual COPA device to look at and hold. All attempts were made by the interviewer to ask and receive answers to all questions. If the participant refused to answer a question or the question was skipped by the interviewer due to time constraints, then the answer was left blank and not included in the analyses. The interviewer was also permitted to probe on questions as needed.

Participants were asked questions about the specific attributes of the COPA system, expected storage of the device and if that would be a concern, interest in using COPA, the impact of receiving more take-home methadone for longer periods, impact on quality of life/likeliness to continue treatment/productivity at work, interest in paying to use the device, and how much the participant would be willing to pay to use COPA. When answering questions with numerical answers (e.g., amount willing to pay, time to get to the clinic), if answers were given in a range (e.g., 40–50), the mean of the two numbers was used for the patient to obtain overall means or medians (e.g., for an answer of 40–50, 45 was used for that answer). When asked about a value per month, if the participants gave an answer of a value per week, the per week answer was multiplied by 4.5 to complete a monthly value.

Data collection and reporting. All participant interview information was collected by an independent company (4C Research Group) and was de-identified and summarized for reporting purposes. Quantitative data was summarized using descriptive statistics (n, mean or median, minimum/maximum, and/or percentage). Direct quotes from interviews were selected to represent specific concepts conveyed by patients in interviews. 

Results

Background information and characteristics. Detailed information on the participant demographics and methadone characteristics are listed in Table 1. All participants (n=12) traveled by car to the clinic, and all participants were on a single dose of methadone per day. The mean time it took a participant to achieve more than one day of take-home methadone since starting the medication was 23.57 months, with a median time of one year (range: 1 month–3.5 years). Participants who had 2 to 5 take-home doses reported it took them an average of 21.5 months (range: 2–36) to achieve their first expanded take-home dose, and those with six or more take-home doses reported an average of 26.3 months (range: 1–42 months) to achieve their first expanded take-home dose. 

Perspectives on take-home doses of methadone. All participants reported they were aware of the requirements for obtaining take-home methadone doses. Participants largely believed that the take-home requirements of the OTP clinic were appropriate (75%, n=9/12), but 25 percent (n=3/12) believed the clinic requirements were too strict. Reasons for appropriateness of requirements included the patient needing to show they are accountable and would not sell or abuse the methadone and safeguards (e.g., clean drug screens and drug interactions) for the clinic to grant take-home methadone. No participants mentioned that the requirements were not strict enough. Most participants receiving take-home doses (71.4%, n=5/7) stated they had take-home requirements explained to them when they first started treatment, with the remaining two participants (28.6%) having it explained to them later in treatment. 

Most participants (91.67%, n=11/12) expressed interest in having a larger number of take-home doses. The single participant (receiving ≥6 doses per week) who stated they did not wish to have more take-home doses explained they were not interested in more methadone doses due to an expressed fear of having their take-home doses stolen and an appreciation of their weekly visit as part of their routine.

When asked specifically about benefits of having take-home doses, participants confirmed that take-home doses reduced frequency of clinic visits (n=5/12; 41.67%), had less of an impact on work (n=8/12, 66.67%), provided more flexibility (n=9/12, 75.0%), and reduced costs associated with transportation (n=3/12, 25.0%). When probed on the benefits of take-home methadone, out of the 10 participants who responded to the question, 50 percent confirmed being able to sleep in or have more free time in the morning, 80 percent confirmed that take-home doses made it easier to get to work on time or keep their employment, and 40 percent confirmed their ability to travel and go away on vacation. One participant noted (unprompted) that going to the clinic daily was “just a reminder that you’re on the fringes of society and you’re going to the methadone clinic” (Table 2) and that the patients are “in this group of people that are considered to be addicts and criminals.” 

The mean time spent between travel to the clinic and time for dosing/bottle preparation was 75 minutes (range: 30–180), with a mean travel time of 15 minutes (range: 10–50; Figure 3A). Participants spent on average $36.58 per trip on transportation to the clinic (range: $15–80; Figure 3B). Those without expanded take-home doses spent an average of $40.80 per trip (range: $15–80), those with 2 to 5 take-home doses spent an average of $27.50 per trip (range: $15–40), and those with six or more take-home doses spent an average of $41.66 per trip (range: $25–70).

Fifty percent of participants (n=6/12) believed that reducing the number of clinic visits would improve their ability to take methadone and improve their treatment, 41.67 percent (n=5/12) believed it would improve their ability to care for family and loved ones, and 83.33 percent (n=10/12) believed it would make it easier for them to maintain their ability to work (1 participant was unemployed at the time of the survey). 

When asked if participants would split the dose of their daily methadone if it expanded or increased their take-home privileges, 54.54 percent of participants (n=6/11) noted they would be willing to split their methadone dose into two dosing times per day. Three participants noted spontaneously in the interview that splitting the dose to twice per day would be beneficial because they did not feel the dose effect lasted the full 24 hours. One participant did not answer this question.

COPA perspectives. Overall, response to COPA was positive (Figure 4). Sixty-seven percent of participants (n=8/12) said they would use the COPA if the clinic recommended they use it, whereas 33.33 percent (n=4/12) said they would not. For those who indicated they would not use the COPA system, the most common reasons given were concerns about uncertainty or reliability of the technology (n=2), lack of comfort with changing their current method of methadone administration (n=2), and waiting until it had been used by others (n=1). Of those asked in the interview (n=5), four participants said they believed the device would help them continue their medication-assisted treatment, and all five said it would make it easier for them to work or improve their productivity at work. 

Eighty percent of participants (n=4/5) who did not have take-home privileges stated they would be willing to pay a mean of $126.88 per month (range: $30–225) out of their own pocket to use the COPA system if it would enable them to start receiving doses. Of participants with take-home privileges, 57 percent (n=4/7) were willing to pay to use the COPA system if it maintained their current number of take-home doses, at an average of $30.31 per month (range: $20–45). Of those who had take-home privileges, 100 percent (n=7/7) would pay out of their own pocket to use COPA if it would enable them to expand their take-home doses and reduce the frequency of their trips to the clinic, with a mean response of $117.50 per month (range: $40–247). The mean amount of money patients were willing to pay across all groups and instances for the COPA was $96.75 (range: $20–247).

None of the participants felt that storage of the COPA device would be a concern in their living situation, nor did they feel concerned the device would get lost or stolen. 

Participants largely perceived the attributes of COPA as positive (Figure 4). Patients showed positive responses toward the following attributes: dose pausing if the participant’s mouth was removed from the device (92%, n=11/12), providing the correct dose without measuring (92%, n=11/12), cellular connectivity (92%, n=11/12), transmitting data about the dose (83%, n=10/12), fingerprint and teeth identification (75%, n=9/12), rechargeability (75%, 9/12), email and/or text reminders to take a dose (75%, n=9/12), prespecified range of time for dose to be taken (67%, n=8/12), and email/text reminders and notices sent from the system to others identified by the patient to take a dose (50%, n=6/12). Two participants also spontaneously noted they believed no one would likely know what the device was for, thereby not making it a target for being stolen.

Concerns noted about COPA mostly included issues regarding function of the device (not trusting the appropriate amount of dose would be released), concerns over missing the dosing window (vs. the flexibility of having a take-home dose that does not have a time restriction or going to a clinic with a large dosing time window), and concerns over the ability of the device to send information to the clinic when no cell service is available, not transmitting completed dosing information properly, or having to remember to charge the device. 

Discussion

Methadone has a long history of being an efficacious for the treatment of OUD, but limitations to appropriate access include lack of available clinics, requirements to come in for daily treatment distribution, concerns over diversion, and stringent requirements for take-home doses at the federal, state, and clinic levels. Attending an OTP clinic for methadone treatment also has an impact on patient quality of life and sense of self-worth.²³ While take-home doses are a potential solution to the limitations that clinics impose, there are often concerns about misuse, abuse, and diversion; there is a crucial unmet need for solutions that allow for convenient methadone dosing for OUD while addressing these concerns. Decreasing time and monetary requirements for dosing and increasing quality of life and dignity of patients taking methadone could also improve adherence and treatment success. This includes increasing the ability to offer methadone to high-risk patients, including those in jails, prisons, hospitals, and skilled nursing facilities,¹⁶ as well as patients in rural areas or areas where there is no easily accessible OTP clinic. 

The COPA system uses a handheld device with dual biometrics that confirm methadone is dispensed to only the appropriate and intended user (the patient), along with remote management and advanced data analytics to increase medication adherence and long-term patient treatment retention. The COPA has capabilities to give scheduled dosing reminders and can send alerts back to the HCP in case of a missed dose or attempts to dose outside the intended dosing time or by a person other than the patient. Thus, it is a potential solution to many of the current limitations of liquid methadone administration. 

This single-site survey demonstrated there was a high interest in more take-home doses, even from participants who were already receiving six or more days of take-home doses. The survey also confirmed the negative impact of visiting the clinic found in previous studies, including challenges with keeping a job/arriving to work on time, cost to visit the clinic, inability to travel outside of the local area, and negative psychological impact (e.g., feeling like a criminal or addict). 

Participants had a strong understanding of take-home requirements and the reasons for them. They also noted the positive impact of take-home doses on the ability to attend work/school or travel. The study also documented the impact of traveling to and from the clinic on the participant, including considerable time spent on and costs of transportation, despite the clinic being in a suburban area with all participants having access to a car. In this study, participants who had the longest commute to the clinic had more take-home doses, potentially due to a higher motivation to not come into the clinic on a daily basis. As noted previously, OTP clinics can be sparse and not close to a person’s home. COPA is a secure at-home solution that could reduce the number of times the patient needs to come to the OTP clinic while improving adherence and security and reducing misuse for patients using methadone for OUD. 

It took participants an average of 23.57 months to achieve their first take-home dose (median: 12 months, range: 1 month–3.5 years), which represents the large cost and time burden on OTP clinics and patients to complete daily dosing prior to the patient achieving take-home doses. The COPA system could also assist in the reduction of time to take-home privileges due to the attributes of the system that ensure appropriate dosing and reductions in diversion.

Interestingly, several participants spontaneously expressed a preference for split-dosing due to the effects of methadone waning while on a once-per-day regimen. This has not been previously well-documented as an unmet need for patients, but it deserves attention for this population to ensure the success of treatment and reduce the chances of withdrawal symptoms and relapse. Dosing of methadone more than once per day is also not made readily available for patients in the current OTP environment, with the exception of those who are pregnant or have a documented need due to having a higher metabolism (which is not routinely tested). Increasing patients to twice-daily dosing with take-home bottles or additional clinic visits is also not an efficient or cost-effective pathway due to cost and burden on the patient and clinic. However, with the convenient capability of delivering more than one dose per day remotely, the COPA system could be a solution for patients who would benefit from multiple doses per day, without adding the burden of taking home more bottles or coming into the clinic more often. A patient receiving 100mg or less of methadone per day could be given the COPA device and one bottle that could last for six days; patients needing more than 100mg could be given two bottles for use.

The study also demonstrated that COPA was seen as a positive and useful tool, as participants had largely positive responses to its attributes. Participants did not receive training on the setup and usage of the device, which would likely mitigate most of the concerns mentioned by the participants when discussing their willingness for usage (including technical uncertainties or ease of use). 

Our survey also showed that participants were largely willing to pay for the system to maintain or expand their doses of take-home methadone. This demonstrated a personal willingness to invest in their treatment and, among participants already receiving take-home doses, a preference for COPA over take-home bottles, potentially due to convenience and safety of the device. Participants were also not concerned about losing or having someone steal the device. Participants noted that the device does not have an obvious appearance for methadone administration, which improves the anonymity of taking methadone; this suggests that COPA could also help to maintain patient dignity and improve the administration experience, thereby reducing patient concerns over the stigma of utilizing methadone for OUD.

Limitations. Participants were sampled from a single, large OTP clinic in a suburban area, and all participants used a car to get to the clinic. The clinic supplied a take-home dose for Sundays to most patients who were included in our no take-home group, and patients of the study clinic had the ability to be granted take-home privileges after meeting requirements for 30 days; these requirements might vary for other clinics. The participants were largely Caucasian, and the study had a small sample size. Data on socioeconomic status were not collected, which could affect patient willingness to pay for a device. Qualitative themes were identified after the interviews were completed, and the study did not use a validated questionnaire. Because of these limitations, the study findings are not generalizable to all patients and clinics in the US, especially those in urban or rural areas or with more restrictive requirements for take-home dosing. Participants might have also transferred from other clinics with different requirements for take-home doses, impacting their interpretation of the requirements and the duration to their first take-home dose with the study clinic. Completing an interview-based study with a researcher in-person that was on a sensitive topic may have also impacted participants’ responses. Larger studies with an expanded patient base, stratified by different socioeconomic levels and areas of residence, with a variety of ethnicities could be beneficial to expand these findings. However, the current findings on the impact of methadone take-home doses and attending an OTP clinic largely reflect findings of other published studies on the topic. 

Conclusion

Visits to the OTP clinic for methadone dosing or refilling of bottles can have a negative impact on patients, including economic, time, and emotional impacts. Participants appreciated take-home dosing, and almost all participants preferred to expand their duration of take-home doses. Expanding access to take-home doses, the ability to split doses, and increasing the duration of take-home doses while maintaining communication with the clinic and ensuring security of methadone dosing would be highly beneficial to patients. Participants had an overall positive perspective of COPA, and most expressed interest in investing their own funds to use it if it would enable them to receive or increase their take-home methadone doses. 

Having a secure option for methadone administration that ensures the correct dose is taken by the intended patient at the intended time could provide benefits to the clinic and patients alike, including improving adherence and compliance with remote monitoring, providing multiple dosing options, expanding access to methadone to more patients, allowing clinics to address skipped dosages in real-time, and potentially improving the efficacy of treatment. Usage of COPA could therefore result in increased patient retention in OUD treatment with the use of a system that is preferred by patients.^26,27

The COPA system could be a solution to the challenges of methadone administration and would likely be welcomed by many patients. The system could provide solutions concerns about take-home doses by ensuring that only the patient receives the dose, along with ensuring security and confirmation of dosing, while increasing the ability to expand take-home dosing to more patients. These attributes are especially crucial in areas where OTP clinics are not readily available or where clinics wish to expand access and reduce the impact of methadone use on patient’s lives. 

References 

1. Dydyk AM, Jain NK, Gupta M. Opioid use disorder. In: StatPearls. Treasure Island (FL): StatPearls Publishing; 2024.
2. Vallersnes OM, Jacobsen D, Ekeberg Ø, et al. Mortality, morbidity and follow-up after acute poisoning by substances of abuse: a prospective observational cohort study. Scand J Public Health. 2019;47(4):452–461.
3. Ahmad FB, Cisewski JA, Rossen LM, et al. Provisional drug overdose death counts. National Center for Health Statistics. Reviewed 16 Oct 2024. Accessed 30 Oct 2024. https://www.cdc.gov/nchs/nvss/vsrr/drug-overdose-data.htm 
4. American Medical Association. AMA overdose epidemic report. 8 Nov 2023. Accessed 30 Oct 2024. https://www.ama-assn.org/system/files/ama-overdose-epidemic-report.pdf
5. Kosten TR, George TP. The neurobiology of opioid dependence: implications for treatment. Sci Pract Perspect. 2002;1(1):13–20.
6. Durrani M, Bansal K. Methadone. In: StatPearls. Treasure Island (FL): StatPearls Publishing; 2024.
7. Kling MA, Carson RE, Borg L, et al. Opioid receptor imaging with positron emission tomography and [(18)F]cyclofoxy in long-term, methadone-treated former heroin addicts. J Pharmacol Exp Ther. 2000;295(3):1070–1076.
8. Kreek MJ. Methadone-related opioid agonist pharmacotherapy for heroin addiction. History, recent molecular and neurochemical research and future in mainstream medicine. Ann N Y Acad Sci. 2000;909:186–216.
9. Schluger JH, Borg L, Ho A, et al. Altered HPA axis responsivity to metyrapone testing in methadone maintained former heroin addicts with ongoing cocaine addiction. Neuropsychopharmacology. 2001;24(5):
   568–575.
10. Wakeman SE. Diagnosis and treatment of opioid use disorder in 2020. JAMA. 2020;323(20):2082–2083.
11. Joseph H, Stancliff S, Langrod J. Methadone maintenance treatment (MMT): a review of historical and clinical issues. Mt Sinai J Med. 2000;67(5-6):347–364.
12. Morey SS. NIH consensus panel advocates increased access to treatment for opiate addiction. Am Fam Physician. 1998;58(3):
    786–789.
13. Effective medical treatment of opiate addiction. National Consensus Development Panel on Effective Medical Treatment of Opiate Addiction. JAMA. 1998;280(22):1936–1943.
14. Teoh Bing Fei J, Yee A, Habil MH, et al. Effectiveness of methadone maintenance therapy and improvement in quality of life following a decade of implementation. J Subst Abuse Treat. 2016;69:50–56.
15. Knopf A. First-of-a-kind OTP census shows vast majority of patients treated with methadone. Addiction Treatment Forum. 5 Dec 2022. Accessed 30 Oct 2024. https://atforum.com/2022/12/otp-census-patients-methadone/
16. Krawczyk N, Joudrey PJ, Simon R, et al. Recent modifications to the US methadone treatment system are a band-aid-not a solution-to the nation’s broken opioid use disorder treatment system. Health Aff Sch. 2023;1(1):qxad018.
17. Bell J, Strang J. Medication treatment of opioid use disorder. Biol Psychiatry. 2020;87(1):82–88.
18. Hancock H, Mennenga N, King H, et al. Treating the rural opioid epidemic. National Rural Health Association. 2017. Accessed 30 Oct 2024. http://www.antoniocasella.eu/archila/Hancock_2017.pdf
19. Amiri S, Greer MD, Muller CJ, et al. Disparities in access to radiation therapy by race and ethnicity in the united states with focus on American Indian/Alaska Native people. Value Health. 2022;25(12):1929–1938.
20. DePetrillo PB, Rice JM. Methadone dosing and pregnancy: impact on program compliance. Int J Addict. 1995;30(2):207–217.
21. Braun HM, Potee RA. Individualizing methadone treatment with split dosing: an underutilized tool. J Subst Use Addict Treat. 2023;152:209096.
22. Bromley L, Kahan M, Regenstreif L, et al. Methadone treatment for people who use fentanyl: recommendations. Toronto, ON: META:PHI; 2021. Accessed 30 Oct 2024. https://www.metaphi.ca/wp-content/uploads/Guide_MethadoneForFentanyl.pdf
23. Frank D, Mateu-Gelabert P, Perlman DC, et al. “It’s like ‘liquid handcuffs”: the effects of take-home dosing policies on methadone maintenance treatment (MMT) patients’ lives. Harm Reduct J. 2021;18(1):88.
24. Ward J, Bell J, Mattick RP, et al. Methadone maintenance therapy for opioid dependence. CNS Drugs. 1996;(6):440–449.
25. Hoffman KA, Foot C, Levander XA, et al. Treatment retention, return to use, and recovery support following COVID-19 relaxation of methadone take-home dosing in two rural opioid treatment programs: a mixed methods analysis. J Subst Abuse Treat. 2022;141:108801.
26. Pani PP, Pirastu R, Ricci A, et al. Prohibition of take-home dosages: negative consequences on methadone maintenance treatment. Drug Alcohol Depend. 1996;41(1):81–84.
27. Pani PP, Pirastu R. Take-home and compliance with methadone maintenance treatment. Heroin Addict Relat Clin Probl. 2000;(1):33–38. 
28. Qian G, Humphreys K, Goldhaber-Fiebert JD, et al. Estimated effectiveness and cost-effectiveness of opioid use disorder treatment under proposed US regulatory relaxations: a model-based analysis. Drug Alcohol Depend. 2024;256:111112.
29. Roy V, Buonora M, Simon C, et al. Adoption of methadone take home policy by US state opioid treatment authorities during COVID-19. Int J Drug Policy. 2024;124:104302.
30. Substance Abuse and Mental Health Services Administration. 42 CFR part 8 final rule. Updated 31 Jan 2024. Accessed 30 Oct 2024. https://www.samhsa.gov/medications-substance-use-disorders/statutes-regulations-guidelines/42-cfr-part-8
31. Madden EF, Christian BT, Lagisetty PA, et al. Treatment provider perceptions of take-home methadone regulation before and during COVID-19. Drug Alcohol Depend. 2021;228:109100.
32. Goldman FR, Thistel CI. Diversion of methadone: illicit methadone use among applicants to two metropolitan drug abuse programs. Int J Addict. 1978;13(6):855–862.
33. Figgatt MC, Salazar Z, Day E, et al. Take-home dosing experiences among persons receiving methadone maintenance treatment during COVID-19. J Subst Abuse Treat. 2021;123:108276.