1.Introduction
The misuse of opioids is endemic across the modern world and responses to the issue vary from country to country. In 2015, there were 1.3 million opioid users in Europe and 191,000 of those users were undergoing treatment (1). That year in Ireland, 9,917 substance abusers were commenced on drug addiction treatment, 4,000 of them for the first time (2). Despite there being over 300 drug treatment centres and more than 360 specialised General Practitioners “GP” providing methadone maintenance treatment “MMT”, (2) the number of cases being treated in Ireland decreased by almost 13% between 2009 and 2015 (1). In addition to these figures, Ireland is included in the top 8 European countries with the highest rates of drug-related mortality, despite having a large proportion of substance misusers in treatment (see Figure 1). This indicates that MMT is not working as efficiently as is required (2).
Figure 1: Proportion of opioid users undergoing substitution treatment (3).
MMT and buprenorphine are the standard treatment options for opioid addiction in Ireland and internationally (4-6). Methadone is a substituting pharmacological agent, which suppresses the withdrawal symptoms and cravings associated with opioids as well as increasing one’s tolerance to opioids (7-9). The use of MMT is well established worldwide. In a systematic review comparing three RCTs investigating supervision and opioid dependence, MMT was found to be more effective than detoxification or counselling (6, 10). MMT alleviates the social and health burden of opioid abuse in many countries by reducing mortality, crime and blood borne diseases (7, 11-20). However, it generally involves long-term treatment and therefore retention in treatment is critical (9).
Recommended by the World Health Organisation and implemented in Ireland, methadone is consumed under the supervision of a health care professional (6). In Irish primary care settings, guided by the Irish College of General Practitioners “ICGP”, a minimum of one dose per week is to be supervised with no more than six take home doses dispensed (4, 21). Under Irish legislation, GPs must have a level one or level two qualification to prescribe methadone. Level 2 GPs are responsible for methadone treatment initiation and can have up to 35 patients under their care. While Level 1 GPs can prescribe to a maximum of 15 stabilised patients who have already instigated treatment with a level 2 GP (22). Recommended by the HSE and employed in the UK and other countries, a patient in the first phase, ‘stabilisation’, should be supervised frequently for up to three months (4, 17, 23-25). In the subsequent maintenance phase, supervision requirements are reconsidered if the patient’s behaviour is considered ‘stable’. Stability is described as a ‘pharmacological equilibrium’ whereby a sufficient dose of methadone has been prescribed to prevent withdrawals and intoxication (15). Clinicians report key elements of stability as negative drug-urine samples, employment, programmatic adherence, cessation of injecting behaviours, external support and physical and psychosocial well-being (15, 26, 27). However, when utilising these assessments, it cannot be assumed that stability is synonymous with suitability for unsupervised dosing.
Supervised consumption was brought into practice in the 1990’s (28) with the intention to reduce diversion of doses, mortality and to ensure the medication is taken as directed (17, 29). Supervised consumption entails a health care professional “HCP” observing the patient consuming the methadone orally on the premises, usually in a pharmacy setting (17). It has been remarked across a number of observational studies that regions with high supervision requirements are associated with lower methadone-related death rates (21, 30, 31). Zador 2006, commented on the study by Morgan et al. on the association between the availability of heroin and methadone and fatal poisonings, that an increase from nil to 36% of supervised doses was linked to a 75% death reduction in the UK between 1995 and 2005 (32-34). This association is reflected in a number of other studies (28, 30). It should be noted that these effects are likely to be applicable primarily to those not in treatment (21).
The reduction in deaths is likely to be associated with the decreased rate in diversion. Diversion is described as the unsanctioned supply of regulated pharmaceuticals from legal sources either to the illicit drug market or to a user for whom the drugs were not intended (15, 35). Diversion results in a number of poor outcomes such as; continued opioid abuse, treatment failure, overdose and increased methadone availability to the general public (26).
Despite most literature suggesting that increasing supervision decreases diversion, an RCT by Holland et al. comparing retention under different supervision constraints, documented that 5% of supervised participants and only 2% of the unsupervised participants admitted to sharing their medication. However, self-report was utilised to assess this which is inherently inclined to under-reporting. Moreover, it was not specifically stated that diversion had occurred, therefore making the validity of this statistic dubious (36). Furthermore, in a study carried out in Dublin probing illicit methadone use, 55% of people in MMT reported to using methadone illegally and 73% reported use before being in treatment suggesting that diversion of supply is prevalent (37). As methadone related deaths are mainly due to illicit use and overdose (38) it is important to minimise diversion by finding a balance in supervised and unsupervised consumption (21, 28).
Opioid dependence is a complex condition, which usually requires long-term treatment with methadone. In order for MMT to be a successful treatment, retention is imperative. If the patient is not retained and withdraws from treatment prematurely, there is an increased risk of mortality, particularly in the first month post treatment cessation (19, 21, 39).
Few trials have compared the effect of supervision on treatment retention and appear to have inconsistent and paradoxical results (24, 29, 36, 40, 41). An RCT in the US examining methadone dose and visit frequency, with the outcome being retention, established that 5 days of supervision per week yielded high dropout rates compared to 2 days of supervision (40). However, there were numerous alternate factors that influenced this including the dose prescribed and age of the patient. Subjects on a higher dose of methadone were retained irrespective of supervision requirements (40). This relationship between retention and dose is consistent across studies (7, 22, 42, 43).
A pilot RCT conducted by Holland et al. compared the retention rates of twice weekly supervised consumption, daily supervised and unsupervised consumption over a three-month period (24). The results must be considered tentatively as they were not deemed statistically significant due to under powering the study. Nevertheless, relevant themes emerged that are considered to be of importance for the proposed trial. In the RCT, daily supervision yielded the poorest retention rate, whilst unsupervised was most successful with regard to retention. However, there was an intermediate effect seen when supervised twice weekly, differing to unsupervised retention rates by just 3% (24). This provokes the question of balance between retention, which appears to be directly correlated with reduced supervision, against a possibility that lower levels of supervision may lead to higher diversion.
Another RCT by Holland et al. compared 3 months of supervised consumption with one month of supervised consumption followed by no supervision. After 3 months, there was a 5% difference in retention between the two arms, favouring the unsupervised group, and at 6 months retention was similar in both groups. This study implied that supervision did not affect retention. However, 20% of the participants did not receive the allocated treatment so the validity is treated cautiously (36). A similar RCT in Australia compared supervised versus unsupervised administration of buprenorphine-naloxone and noted that treatment with supervision was as effective as treatment without supervision (29).
Finally, a cohort study by Cousins et al. demonstrated that the relationship between supervised consumption and treatment retention generates a J-shaped curve. High retention rates were observed in groups with 20-60% supervision, while above or below this, retention was reduced (41). This supports the aforementioned findings from Holland et al. (2012) and Rhoades et al. (24, 40). A Cochrane systematic review carried out in 2017 examining supervision in opioid dependence, concluded that the question of effectiveness regarding supervised versus unsupervised dosing was still largely unanswered (10).
While it appears that some supervision may be beneficial with regard to retention and to minimising diversion, the overall consensus is that patients’ preference is unsupervised consumption (18, 24, 44, 45). It is reported that supervised consumption insinuates a lack of trust and is demeaning for the patient (18, 26, 45). Despite patients actively seeking treatment from primary care, the association with substance misuse still remains evident and brings with it a plethora of impediments such as stigmatism when having to be supervised in a community pharmacy (18, 24, 45). In addition to this, the time constraints of the service can be a burden to patients and a deterrent from treatment (18, 45). The restriction of attending a pharmacy daily is an inconvenience and impractical in terms of employment, other commitments or travel requirements which could potentially postpone or prevent the patients from ‘normalising’ their lives (15, 24, 41).
Although lacking an evidence basis, it is assumed that regular contact with a healthcare professional aids retention (26, 41, 45, 46). Supervision proposes to increase medication adherence, prevent diversion (15) and assess the well-being of the patient on a regular basis (18). Those who are poorly compliant or at risk of overdose can also benefit from supervision and appreciate the routine in an often-chaotic life (45). Additionally, it serves as a reintegration tool for users into the community and curtails marginalisation (27).
Research on the use of supervision requirements in Ireland is currently lacking. Consequently, this paper sets out a protocol for evaluating the effectiveness of supervised methadone consumption on treatment retention for methadone patients in primary care. This would facilitate the gathering of a robust evidence base that could be used to guide clinical decision making, and future policies, consistent also with the five goals of the Governments’ strategy for reducing harm and supporting drug recovery 2017-2025 which places emphasis on evidence based data (47). This study also seeks to examine the effect of supervised consumption on the rate of diversion and illicit substance use while on MMT. A qualitative interview will also be carried out to explore the patient’s perspective on the trial.
2. Study Aims and Objectives
The purpose of this study is to compare the effectiveness and acceptability of different models of supervision of methadone after the initial 3 months of treatment stabilisation. The primary outcome of the trial is retention in treatment at 6 months. Three different models of supervision will be investigated;
¬ Daily pick up with supervised consumption on two days per week;
¬ Daily pick up with one day per week supervised;
¬ Daily pick up with no supervision (as the control).
Secondary objectives are to include and evaluate the safety issues associated with different supervision practices, namely; the diversion of methadone and the effectiveness of the treatment with regards to abstaining from illicit drug use. Additionally, an interview discussing the patient’s experience with regard to supervision during the trial will provide a qualitative rationale behind the effectiveness of each intervention.
3. Methods
3.1 Study design, setting
This study will be a cluster randomised control trial based in primary care facilities, namely general practitioners and community pharmacies across both rural and urban Ireland. It will take the form of a three-arm cluster RCT developed in accordance with Standard Protocol Items, Recommendations for Interventional Trials (SPIRIT) guidelines. In order to avoid contamination across different arms, a cluster RCT was designed with the unit of randomisation being GP practices offering MMT. The patients receiving the interventions will be the unit of analysis in terms of retention, diversion, illicit substance use and reported outcomes.
3.2 Participants and recruitment
Eligible GPs would be those with a minimum of level 1 methadone qualification with at least 10 patients on their patient panel. Those GPs meeting the criteria will provide a list of suitable participants from their practice. Patients will be offered the opportunity to participate in this study should they meet all the inclusion criteria.
3.2.1 Patient inclusion criteria
Eligible participants will consist of those with a clinically diagnosed opioid addiction and have initiated methadone substitution treatment for a minimum of 3 months prior to recruitment for stability reasons. These patients should only be considered if they are ‘stable’ as defined in this trial as; having permanent housing, stabilised on a dose, negative drug urine samples, socially functioning and engaged in treatment thus far. Ultimately this decision will be at the discretion of their respective GP. The patients will be informed of the trial by trained personal discussing the patient information leaflet (see Appendix 2A). They will be given as much time as needed to read it and ask questions. Following this, they will provide written consent (see Appendix 2B). As suggested by Holland et al., an extended timeframe will be permitted in order to identify eligible patients within practices (24).
3.2.2 Exclusion criteria
Consistent with previous trials participants will be excluded if they are pregnant, breastfeeding, under 18 years old, homeless, on a methadone dose of over 120mg or has a complex medical or psychiatric comorbidity which could impair their ability to participate (24, 29, 36, 48). Due to potential safety and storage issues, patients with young children or infants will also be excluded. In this trial, any patient that has been enrolled in previous trials or has been on MMT before will be excluded.
3.2.3 Recruitment
All suitable GPs will be identified from the Irish College of General Practitioners’ list and invited to participate by email or letter as applicable. The email/letter will include an information leaflet outlining the trial. Since our inclusion criteria states that only first time MMT patients and those who commenced treatment in the last 3 months are eligible, the potential population size is restricted. Therefore, in order to get the desired sample size of patients, all GP practices that agreed will be included in the trial.
Each GP will put forward a list of patients fulfilling the criteria in his/her practice. These patients will be sent a letter of invitation to the trial, a detailed information leaflet and a consent form. Following enrolment, the participants designated pharmacy will be informed of the trial. Baseline characteristics will be obtained for each patient in the practice (see Section 3.6). Randomisation of the practices will be carried out by the Trial Coordinator to randomly allocate each practice to one of the three intervention arms using a random computer generator programme. It will not be possible to blind the patients or GPs in this trial (see Section 3.8.3). The protocol and strategy for the patients over the 6-month period can be seen in Figure 1.
Figure 1: Flow chart of trial.
3.3 Intervention
There will be three interventions groups in this trial. Group one will receive methadone from their appointed pharmacy on a daily basis. These will be required to consume their daily dose on the pharmacy premises twice weekly (see Figure 2). The supervised days will be assigned at the beginning of the trial and will be specific for each patient to avoid an overload of patients on the same day. Adjustments will be allowed in order to facilitate the participant’s schedule. Supervision will entail swallowing the liquid methadone in the presence of a designated pharmacist. Similarly, group two will be required to pick up their methadone daily, but will only be supervised once weekly. Finally, the control group, group three will pick up their methadone daily but will be exempt from any supervision requirements. For all groups, daily pick up of medication will exclude Sundays, in which an extra take home dose on Saturdays will suffice due to opening hours. Irrespective of group allocation, all participants will see their GP weekly for a new prescription and a random drug urine test will be carried out every two weeks.
Figure 2: Intervention arms
3.4 Discontinuation criteria
Discontinuation will be considered if there becomes a risk of a child being in contact with the methadone. Alterations to group allocation or discontinuation of a specific patient can be made at the prescriber’s request (36).
3.5 Outcomes
3.5.1 Primary outcome
The primary outcome will be retention in treatment at 6 months from the date the patient entered the trial. Irish guidelines state that methadone prescriptions should not be for more than 7 days (4, 41), therefore to be in treatment patients must be receiving a new prescription from their GP each week. Thus, retention in this trial will be defined as a patient attending their GP every week and adhering to treatment over the course of 6 months.
3.5.2 Secondary outcomes
Secondary outcomes will investigate diversion, abstinence from illicit drug use, and qualitative patient reported outcomes. A drug urine test will be carried out at random every two weeks in all intervention arms, to monitor illicit drug use. In conjunction with the urine analysis, the Maudsley Addiction Profile (MAP) questionnaire (see Figure 3) will be employed to further track substance misuse (24, 27, 36, 48-50). This is a validated questionnaire and is used in similar trials such as Holland et al. and Jaffray et al (24, 36, 50).
Semi-structured qualitative interviews will be conducted looking into diversion, as well as the patient reported outcomes in relation to the trial experience both positive and negative. In accordance with the trial by Anstice et al., examining client issues and stigma, the interviewer will assess various topics using open-ended questions, some of which will include expectations and satisfaction with treatment, the general experience of receiving the intervention, misuse of medication, diversion of take home doses and their thoughts on supervision (18, 24, 51). The interviews will be audio-recorded, and will then be transcribed by an independent researcher, as appointed by the Trial Coordinator. The interviewing method carried out by Oviedo-Joekes et al. in ‘The North American Opiate Medication Initiative’ will form the basis of this study’s interview and it is anticipated that each interview will last approximately 45 minutes (51). It aimed to investigate the patients’ perceptions of treatment received as will this trial.
Figure 3: Maudsley Addiction Profile Questionnaire.
3.6 Data collection
It is obligatory that each participant provides written consent before the trial commences (see Appendix 2B). Baseline data such as age, demographic profile and drug use will be collected from each participant at the beginning of the trial.
To assess the primary outcome, data of recruited patients will be collected for 6 months from pharmacy dispensing records and GP prescribing records. With regards to the secondary outcomes, data such as urine test results, diversion frequency and patient reported outcomes will be collected throughout the duration of the trial. Section B of the MAP will be utilised to assess the use of other illicit substances (see Figure 3). Topics included in the devised interview will encompass; employment status, stigma, convenience, quality of life, diversion and their general experience of their treatment group. The data from the devised interview will be collected and analysed by blinded researchers, independent of the research team (24, 29, 51).
Patients who are not retained in treatment, and therefore dropped out of the trial, will be followed up by contacting the GP or the participant. If the participant is in prison, has been transferred to another clinic or has died no follow up will be done. Otherwise the participant will be approached by telephone call or delivered a questionnaire via post if possible however this may be challenging as patients may not always reside at the same residence.
All data will be managed and protected in accordance with the Data Protection Act 1998. Hard copies of the data collection forms, and any other documentation will be stored in a password protected vessel by which only assigned authorised personal will have access to. The online database will be heavily password protected on a secure encrypted server in RCSI. For the full data protection protocol refer to Appendix 1 question 11.
3.7 Timeline
It is expected that this trial will last for a total of 32 months. (see Figure 4). Preliminary work such as protocol development is expected to take 2 months, and ethics application to be submitted within this timeframe. Ethical approval will be sought from the Royal College of Surgeons Ireland “RCSI” research ethics committee “REC” initially and then from the HSE National Drug Treatment Centre Board. Ethical approval in both cases is estimated to take approximately 3 months. There will then be an initial 2-month period of recruiting suitable patients from the individual GP practices. The trial will last 6 months for each participant. However, the trial will run for an extended 10-month period in order to continue recruiting patients who reach 3 months of initial stabilisation treatment and where eligibility criteria are met. Data will be collected throughout the six months including drug-urine test results and dispensing records. Collection data will be facilitated through the use of a Data Collection Form (see Appendix 3) and will continue to be carried out for approximately 2 months after trial cessation. Following this, data analysis will occur two months. Project write up will be on going throughout the trial and up to two months after data analysis is complete.
Figure 4: Timeline – Gantt Chart.
3.8 Randomisation
3.8.1 Sequence generation
A computer random sequence generator will be used to randomise the clusters. The unit of randomisation will be the GPs, not the patients. Selection bias is removed by this and increases internal validity.
3.8.2 Allocation concealment & implantation
As a computer sequence generator will be employed to generate the sequence, allocation concealment is guaranteed by the software. The sequence will remain concealed until the GP practices have been allocated and patients recruited as per the trial protocol. The GP will be then made aware of their allocation and subsequently the patients in said practice.
3.8.3 Blinding
Due to the nature of this trial, neither the GP nor the patient can be blinded to their group allocation. This reflects a naturalistic setting for patients. Everyone that fits the inclusion criteria will be recruited therefore limiting selection bias. Participants in all arms will be subject to uniform protocols such as random urine testing, daily medication pick-up and weekly doctor visits. As recommended by Bell et al. and Holland et al., the data collectors and analysts will be blinded to the aim of the trial and to the allocations as well as the GP’s identity (24, 29). In this intervention, it is unlikely that bias will be a problem as urine testing and dispensing records are of their nature certain and verifiable (24).
3.9 Ethical Approval
Ethical approval will be sought from Royal College of Surgeons “RCSI” REC as well as the HSE National Drug Treatment Centre Board. Full ethics application can be seen in Appendix 1.
3.10 Statistical analysis
Baseline data will be described and presented with descriptive statistics, using STATA version 14, to assess differences in the baseline characteristics of GP practices and participants in the three arms of the trial. Significance testing will not be conducted to examine baseline differences between groups as per CONSORT recommendations. The full data analysis will use an intention-to-treat ‘ITT’ approach with participants analysed in the intervention group they were originally assigned to, regardless of the treatment they received.
For the primary outcome, retention in treatment over the 6-month trial duration will be analysed using random effects logistic regression. The individual patient will be the unit of analysis and GP practice will be the random effect to assess differences in the proportion of patients still retained across the three arms of the trial. This allows controlling for baseline covariates and the effects of clustering that may affect the outcome. An odds ratio and 95% confidence interval will also be presented.
With regard to the secondary outcomes, diversion will be presented using random effects poisson regression with the individual as unit of analysis as well as using logistic regression. poisson regression will be used to test whether the intervention groups varied in terms of number of reported diversions. Abstinence from illicit drug use will utilise the same method as that of the primary outcome. The patient experience/ qualitative study will analyse data using a thematic analysis in order to identify key themes.
4.Discussion
Methadone maintenance is itself a complex treatment program involving a diverse challenging group of patients. The literature to date illustrates a high level of uncertainty and varying opinions regarding the most effective, safest treatment for the general population of opioid dependent people. As this particular population is associated with augmented levels of crime, risky behaviour and mortality there is a huge clinical and economic burden placed on Irish health boards. Ireland has a high prevalence of drug users, with an estimated 20,790 opioid users in 2006, a figure which is believed to have increased subsequently and 0.9% of the country’s GDP (2015) spent on drug-related expenditure (2). However, there is no one interventional strategy that has been favoured by clinicians for the general MMT population. The data available thus far doesn’t allow a conclusion to be drawn in regard to what frequency of supervision delivers the highest retention levels in the general methadone population.
Supervised consumption of methadone at least once a week is standard practice in Ireland (4, 21, 41) and has led to a reduction of diversion to the black market, a pattern which is observed across different countries (10, 15, 21, 24, 25, 27, 28, 30, 36, 44, 45). This approach ensures that the medication is taken as appropriate and offers the patient a supportive, ongoing relationship with a HCP. However, it is not always well received by the patient as it is intrusive, time consuming and interferes with daily living (18). As the demands of therapy are intensified and health budgets under scrutiny, it is imperative that effective standardised guidelines be developed to ensure efficiency of the MMT.
This study seeks to determine the effectiveness of three varying supervision requirements for patients in MMT; once weekly supervised consumption, twice weekly supervised consumption and unsupervised consumption, each with daily pick up of medication. Although daily pick up of medication can be a burden in itself, this trial will utilise it in all groups in order to isolate and focus on the effects of supervision alone. This study aims to allow implementation of good clinical practice guidelines supported by a sufficient evidence base, both quantitative and qualitative to assist in determining the impact of varying levels of supervision on retention and its impact also on diversion.
Strengths and weakness comparing to other trials:
As with other trials of this nature, blinding of the participants and GPs was impossible which is an apparent weakness in the trial (24, 29, 36). However, measures will be taken to minimise this by blinding the outcome assessors to the intervention arms and to the identities of the GP practices. The lack of blinding is considered a minor issue as urine testing and prescribing/dispensing records are verifiable and unlikely to involve bias (24).
This trial aims to augment the evidence produced in the pilot study by Holland et al. and relate it to the Irish population. From that study, it was acknowledged that this trial will be feasible and had significant rationale and importance. There are marked differences between this trial and the aforementioned trial such as allowing for a longer timeline to increase the validity of the results as well as the sample size being designed to detect a significant statistical difference between intervention arms so inferences can be drawn. The unique strength of this trial will be its patient group. The population is limited to those just entering MMT for the first time. Prior to this, they would have been under high supervision constraints in the stabilisation phase. This will afford us an uncontaminated true response from the patients as they have no preconceived views of their preference regarding supervision. In addition to this, they are relatively stable as a group when compared to the idiosyncratic nature of those in trials that are commenced at the stabilisation phase prior, therefore limiting attrition (29, 36). Similarly, the patients selected from each practice will all be at the same stage of treatment permitting ease of comparison and additionally limiting contamination. The use of a cluster trial further abates this and adopts a naturalistic setting.
Some studies limited their research to cities and areas of high drug abuse, however similar to Holland et al. and Notley et al., we will populate our sample from differing areas, rural and urban, which will increase external validity (36, 45).
A weakness that resonates in many trials, including this, is the role of the doctor and pharmacist. We cannot be certain that the HCP is delivering the treatment as intended, which may significantly affect the outcomes (15, 19, 21). The pharmacist has a crucial role in minimising embarrassment or stigma experienced by the patient under supervision (18, 52). Gourlay et al. explored users experience with methadone and suggested that the relationships with HCPs are heavily allied with treatment outcomes (53). However, assessing this variable falls outside the scope of this study.
Limitations:
There are several potential sources of bias and a number of limitations embedded in this trial. Firstly, misclassification bias can be introduced by a participant changing GP or pharmacy, owing to them being categorised as not retained. As Jaffray stated, in this case the new pharmacy or GP may not be obliging to continue and take part in the study (50). Similarly, if the participant is transferred to specialised facilities, prison, dies or, although unlikely, those who leave the trial on the basis of successful treatment, are classified as not retained in treatment. However, the attending GP should be able to disclose this information and alleviate this risk (19, 21). For any participants falling into these categories, their results will be removed from the statistical analysis, to prevent any contamination. For those that are retained for the full duration of the trial, recall bias may impact the results as their opinion on the usefulness of supervision may revise over time especially as the stability of these patients is considered to be dynamic (15, 45). The opinions of the participants may therefore be difficult to analyse. Performance bias may also be an issue, affording to the non-blinded participants and GPs as mentioned above. As identified in other trials (18, 29), an added limitation is the lack of quantifiable data variables regarding patient reported outcomes. The interview will be unable to assess the relative importance of each outcome, constricting its relevance (18).
Regarding the secondary outcomes, the main limitation is associated with diversion. Firstly, underreporting of diversion is a likely occurrence (44, 54). As Duffy et al. noted, a future study could assess those not in treatment; the main consumers of diverted methadone (44). Larance noted that diverting practices can often be sporadic (15). In some trials reviewing diversion, the frequency of diversion is not disclosed (24, 36). Therefore, regardless of the extent of diversion any participant that has diverted once will be catalogued in the same category as a participant that diverted numerous times. This limitation will be overcome by employing the same format as the MAP questionnaire, recording the number of days and amount of methadone diverted.
Finally, the generalisability of the trial is a limitation in its own right. Due to the specified inclusion criteria only ‘stable’ patients will be recruited, those with homes, no children and no complex co-morbidities. Additionally, this will be tested on first time MMT patients when, in fact, methadone patients have a tendency to drop in and out of treatment (7).
Future studies
This trial attempts to identify the most effective supervision program for patients starting MMT with regards to harm minimisation. Conversely, it does not give information concerning the length that these programs should be implemented for. Literature suggests that contingency management ‘CM’ is the most effective treatment plan and has been recognised by NICE and WHO for its scientific evidence base (4-6). CM operates by rewarding the patient for negative urine tests or good behaviour with take home methadone privileges.
To date, the literature recommends that the first three months of opioid substitution therapy be under supervision (4, 23, 25, 26, 28). After this, it is an area of uncertainty and often CM is implemented or total liberation from supervision. This trial aims to fill the gap between full supervision to contingency management. Prospective trials should consider the duration of the supervision program between the stabilisation phase to CM.
5. Conclusion
By investigating different supervision regimes, it is hoped that transparent guidelines of best practice can be generated. Substance misusers as a population are dynamic and unpredictable, therefore there is great difficulty in finding a uniform treatment plan. The need for flexibility in programs should be recognised when considering any treatment plan for these patients. Nonetheless, having an evidence basis that a large population can adhere to would be of great benefit in terms of health care, the economy and the patients themselves.