37/4 As A Mixed Number
Experience and response to a randomised controlled trial of extended-release injectable buprenorphine versus sublingual tablet buprenorphine and oral liquid methadone for opioid use disorder: protocol for a mixed-methods evaluation
Abstract
Introduction Opioid use disorder (OUD) is a debilitating and persistent disorder. The standard-of-care treatment is daily maintenance dosing of sublingual buprenorphine (BUP-SL) or oral methadone (MET). Monthly, extended-release, subcutaneous injectable buprenorphine (BUP-XR) has been developed to raise handling effectiveness. This study aims to investigate the experiences of participants who accept been offered BUP-XR (evaluation 1), health-related quality-of-life amidst participants who accept opted to receive BUP-XR longer term (evaluation 2) and the experiences of participants allocated to receive BUP-XR or BUP-SL or MET with the offer of adjunctive personalised psychosocial intervention (evaluation 3).
Methods and analysis Three qualitative–quantitative (mixed-methods) evaluations embedded in a 5-middle, head-to-caput, randomised controlled trial of BUP-XR versus BUP-SL and MET in the United kingdom. Evaluation 1 is a iv-centre interview anchored on an OUD-related topic guide and conducted after the 24-calendar week trial endpoint. Evaluation 2 is a ii-centre interview anchored on medications for opioid use disorder-specific quality-of-life topic guide conducted among participants after 12–24 months. Evaluation iii: unmarried-middle interview after the 24-week trial endpoint. All evaluations include selected trial clinical measures, with evaluation two incorporating additional questionnaires. Target participant recruitment for evaluations one and 2 is 15 participants per middle (n=60 and due north=thirty, respectively). Recruitment for evaluation 3 is 15 participants per handling arm (due north=30). Each evaluation will be underpinned by theory, drawing on constructs from the behavioural model for wellness service use or the health-related quality-of-life model. Qualitative data analysis will exist by iterative categorisation.
Ethics and dissemination Study protocol, consent materials and questionnaires were approved by the London-Brighton and Sussex research ideals committee (reference: 19/LO/0483) and the Health Inquiry Authorisation (IRAS project number 255522). Participants volition be provided with information sheets and informed written consent will be obtained for each evaluation. Study findings volition be disseminated through peer-reviewed scientific journals.
Trial registration number 2018-004460-63.
- substance misuse
- qualitative research
- clinical trials
http://creativecommons.org/licenses/by-nc/4.0/
This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC Past-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, whatever changes made indicated, and the use is non-commercial. Run into: http://creativecommons.org/licenses/by-nc/four.0/.
Statistics from Altmetric.com
- substance misuse
- qualitative inquiry
- clinical trials
Strengths and limitations of this study
-
This is a qualitative-quantitative (mixed-methods) study, embedded within a randomised controlled trial, to investigate patient feel of extended-release injectable buprenorphine handling to provide the patient perspective additional to trial outcome measures.
-
The written report will investigate patients' experience and response to extended-release injectable buprenorphine upwardly to 24 months.
-
This report does not recruit from a population attending tertiary sector addiction services across England and Scotland.
-
This research does not written report experiences of people that declined to receive extended-release buprenorphine treatment, although it does aim to investigate discontinuation after report allocation and over 12–24 months.
Introduction
Opioid utilize disorder (OUD) is a debilitating and persistent disorder characterised by continued utilize of non-medical opioids despite adverse physical and psychological harms.i In the Great britain—and most countries with developed healthcare systems—sublingual buprenorphine (BUP-SL; tablet, a partial μ opioid agonist) and oral (liquid) methadone (MET; a full μ opioid agonist) are the standard-of-care daily maintenance treatments.2 In that location is a long-established evidence-base from randomised controlled trials (RCTs) and observational studies for the effectiveness of these medications for opioid use disorder (MOUDs).
MOUD adherence is expected to help patients reduce or abjure from non-medical opioid utilize and improve their wellness and social performance.3 Retentivity in handling is associated with a substantial reduction—but not a complete elimination—in the risk of unintentional fatal opioid poisoning (overdose).four Rates of overdose bloodshed amongst people in and out of MOUD are 1.4 and 4.6 per 1000 person years for BUP-SL, and 2.six and 12.7 per 1000 person years in and out of MET, respectively.5
In England, between Apr 2020 and March 2021, 140 863 individuals accessed National Health Service (NHS) and not-governmental community treatment clinics with OUD.6 Meta-analysis has shown that around 47% of patients consummate episodes of MOUD treatment.6 Several patient-level factors appear to moderate retention. This includes negative attitudes (eg, perceived stigma) towards supervised dosing of MOUD and regard prescribing arrangements as inflexible to their needs.7 Some patients cycle through repeated periods of MOUD admission, discontinuation and readmission. Younger age, cocaine use, lower doses of MOUD and criminal involvement accept been shown to be associated with discontinuation from treatment.8 These associations reflect heterogeneity in the characteristics of the OUD treatment seeking population.9 Circumstantial health and social bug—consequently or independent of OUD—add complication to the planning and delivery of treatment and supporting medical and social services.ten
At that place is a long history of efforts to amend treatment effectiveness for OUD,11 with a contempo call for adaptive measurement-based care.12 thirteen In a contribution to this effort, the pharmaceutical industry has developed long-acting injectable BUP.14 Using ARTIGEL (a polymer delivery applied science), Indivior developed a monthly extended-release depot administered past subcutaneous injection (RBP-6000/Sublocade) now licensed in Commonwealth of australia, North America and several European countries (extended-release, subcutaneous injectable buprenorphine (BUP-XR) herein).15 The Extended-release Pharmacotherapy for Opioid use (EXPO) study is an ongoing, multicentre, open-label, superiority RCT in England and Scotland to determine the effectiveness and cost-effectiveness of 24 weeks of BUP-XR versus BUP-SL and MET (EU Clinical Trials Register: 2018-004460-63). EXPO is conducted in five NHS community habit treatment centres in Due south London (Brixton), Solihull (West Midlands), Manchester, Newcastle, and Dundee. Participants are informed consenting adults (18 years and over) seeking maintenance MOUD. They volition exist randomly allocated to receive BUP-XR (the experimental condition) or BUP-SL or MET (the control status) for 24 weeks (target sample is n=304). At the South London centre, there will be likewise an exploratory report in which patients are randomly allocated to receive BUP-XR and personalised psychosocial intervention or MET or BUP-SL and psychosocial intervention for 24 weeks.
With a 1-calendar week grace flow afterwards randomisation, the primary outcome for EXPO is days of abstinence from all non-medical opioids to the 24-week endpoint combined with upwards to 12 urine drug screen (UDS) negative tests for opioids. Participants will have the option to continue BUP-XR maintenance after the 24-week endpoint for up to 24 months. Secondary event measures include fourth dimension enrolled in treatment, days abstinent from cocaine and illicit/non-medical benzodiazepines, and craving for heroin and cocaine. The EXPO trial protocol has been published.xvi
At that place is emergent qualitative literature on extended-release MOUD. Published evaluations include a qualitative report from Kingdom of norway with 13 patients that have received one to iv doses of extended-release naltrexone (an opioid antagonist) explored reasons for discontinuing treatment .17 Reported reasons for discontinuation included feeling 'unfulfilled' by the handling, with disappointment expressed effectually not achieving abstinence recovery goals, and discovery that treatment did not eliminate opioid cravings.
In contrast, a qualitative study in Sweden with 32 patients enrolled in extended-release buprenorphine reported high treatment satisfaction.18 Patients described a sense of increased freedom in their everyday life, an ability to travel, a sense of normality, reduced stigma and a shift in their identity. There were also negative appraisals including medication side effects, shorter than anticipated medication effects, opioid withdrawal symptoms and cravings which motivated some to go out treatment.
In Commonwealth of australia, 30 patients who were enrolled in the extended-release buprenorphine handling, expressed having more than freedom and the ability to reach study, work and caring roles.19 However, some study participants found it difficult to control their use of other psychoactive substances, and some reported that the inability to divert or sell oral medication increased financial strain. In Scotland and Wales, 11 homeless individuals with experience of extended-release buprenorphine treatment described that they were able to avert people that would chance drug use, and felt a sense of freedom and openness to new opportunities.20
The present study will extend this literature with capture of a wider range of measures, and with longer follow-upwards. A mixed-methods blueprint will exist used to synergise qualitative and quantitative data. Mixed-methods studies take been recommended for the analysis of complex interventions, peculiarly RCTs, where an in-depth exploration of participants' experiences can provide valuable insights additional to the primary and secondary consequence measures.21
An approach underpinned by theory is also important because this provides structure to the comparison of populations and different health related domains, and in this context will help to integrate findings within the wider literature on OUD treatment and health service evaluation.22 A theory-driven, mixed-methods approach was successfully applied to the analysis of cocaine craving in a contempo RCT.23
The present study will draw on theoretical constructs from the 14-Item Addiction Dimensions for Assessment and Personalised Handling (Adapt) musical instrument developed for OUD measurement-based care24; Andersen's behavioural model for wellness service use25 with a focus on how patients regard the utility of MOUD and other health services; and the health-related quality-of-life model (HRQoL),26 which has been applied to the study of many health conditions.27–29
Written report aims are to investigate (ane) the experiences of study participants who accept been offered BUP-XR for 24 weeks (evaluation one); (2) the experiences and health-related quality-of-life of study participants who have opted to receive BUP-XR for 12–24 months (evaluation 2); and
(3) the experiences of report participants who accept been offered BUP-XR or BUP-SL or MET with adjunctive personalised psychosocial intervention over 24 weeks (evaluation three).
Methods and analysis
Study design
This is a 3-evaluation, qualitative–quantitative (mixed-methods) study embedded in a multicentre RCT. All researchers and participants will be unblind.
Qualitative data for each evaluation will be obtained from in-depth, semistructured (topic-guided), audio-recorded, personal interviews with trial participants. Identifiable information will exist anonymised to maintain confidentiality. To mitigate differences in interview style, all interviewers volition receive training (past NL and JM). All interviews volition be transcribed verbatim.
Quantitative information for the report volition be taken from trial measures, including MOUD enrolment condition; BUP-XR injections received; self-reported opioid, cocaine and benzodiazepine use and UDS data; and OUD and cocaine use disorder (CUD) remission status (DSM-v),30 too as several standardised questionnaires included to address study aims. EXPO primary and secondary upshot measures will be tabulated and reported alongside selected quotations from participants to illustrate their responses to interventions.
Each evaluation will have a target sample size that will autumn inside the recommended range for qualitative studies of this kind (ie, xv–thirty interviews),31; but recruitment may exist capped if there is bear witness of data saturation. Data saturation will exist determined through investigator discussion of findings and themes that emerge during the interviews and whether no new themes have been identified. In each report, participants will be offered a GBP20 prepaid card (https://www.b4bpayments.com) to kickoff their time taken to visit the centre for their interview. Analysis of qualitative data will follow iterative categorisation methodology.22
Data collection, analysis and reporting will adhere to the Consolidation Criteria for Reporting Qualitative Studies32 and the Strengthening and Reporting of Observational Studies in Epidemiology33 consensus guidelines.
Patient and public involvement
Patient and public involvement representatives will be consulted throughout the EXPO trial on research design, procedures and reporting of findings. They will be members of the trial steering committee and the information direction commission. In this study, participants volition have the option to review their interview transcript, brand comments and request corrections earlier the assay. They will likewise be able to brand comments on results before publication to ensure this enquiry is grounded in their experience.
Evaluation 1: the experiences of report participants who have been offered BUP-XR for 24 weeks
Procedure and measures
This evaluation will be done at four EXPO centres (Dundee, South London, Newcastle and Solihull) with a target sample of 15 participants per middle (n=60) to investigate participants' views of receiving BUP-XR and their feel and evaluation of its effects. On completion of EXPO's 24-week endpoint, trial participants volition exist approached by a member of the enquiry team who will describe the purpose of the qualitative report, obtain their written consent and conduct a face-to-face ~45 min interview. The interview topic guide volition use the OUD addiction severity, complexity (individual and social functioning) and recovery strengths constructs from the ADAPT. This evaluation will use the following EXPO measures: (i) BUP-XR status at interview (ie, enrolled in ongoing maintenance or discontinued); (ii) the number of BUP-XR injections received ; (3) self-reported opioid, cocaine and benzodiazepine utilize with UDS data for the past three months (which will provide the trial's main opioid forbearance outcome and drug use secondary outcomes); and (4) OUD and CUD remission status. Measures are summarised in table ane.
View this tabular array:
- View inline
Table 1
Schedule of assessments for the three evaluations
Assay
The analysis will exist implemented in iv steps. In the first descriptive step, each transcript will be deductively coded using Suit constructs, with remainder information inductively coded. The codes will so be merged into headings and subheadings working towards an emerging conceptual narrative. This narrative will be displayed in the form of a coding tree to ensure transparency. In the second conceptualising pace, concepts from the descriptive analysis will exist mapped onto the behavioural model for wellness service employ. In the third differentiating footstep, similarities and differences in participant experiences of BUP-XR will exist investigated, highlighting any identified centre-level differences. To mitigate the risk of overgeneralisation and to maintain nuance, concepts will exist colour coded and mapped by EXPO centre. Quantitatively, the primary event and craving measures from the trial volition exist tabulated and reported aslope selected quotations from participants to illustrate response to BUP-XR. In the final externalising step, findings will be merged and evaluated in the context of the extant literature.
Evaluation 2: the experiences and wellness-related quality-of-life of study participants who have opted to receive BUP-XR for 12–24 months
Procedure and measures
This evaluation will be conducted at ii centres (S London and Newcastle) with a target sample of fifteen participants per heart (due north=xxx), to investigate longer-term feel of BUP-XR. Participants completing the 24-week trial endpoint who wish to receive continued BUP-XR maintenance will be eligible. After 12–24 months from original enrolment in EXPO, participants volition exist approached, irrespective of whether they are even so receiving BUP-XR handling. At the centre, a member of the research squad will approach the participant and draw the purpose of the evaluation, obtain their written consent and bear a face-to-face, ~30 min interview. The interview topic guide will follow the structure of the 39-item Opioid Substitution Handling Quality of Life Scale (OSTQOL),34 which captures patients' views of their personal development, mental distress, social contacts, textile well-being, treatment and experience of discrimination. The evaluation will use the following measures: (1) OSTQOL—structured questionnaire for the by month; (2) BUP-XR condition at interview (enrolled or discontinued); (3) number of BUP-XR injections received since enrolment; (iv) cocky-reported opioid, cocaine and benzodiazepine employ with UDS data for the past 3 months; (5) OUD and CUD remission/status; (6) Difficulties in Emotion Regulation Scale–Short Form for the past 2 weeks35 (7) iv-Item Patient Wellness Questionnaire for the by ii weeks36; and (8) the 15-Detail Patient Health Questionnaire assessing somatisation syndromes for the past four weeks.37 Measures are summarised in tabular array one.
Analysis
Assay of the interview transcripts will proceed via descriptive, conceptualising, differentiating and externalising steps (every bit followed in evaluation one). Initial deductive coding will use the concept structure of the OSTQOL. The HRQoL model volition be used in the conceptualising stage to map headings and subheadings onto the constructs of this model. For the quantitative analysis, each of the measures will be tabulated by centre with differences assessed using a conventional 5% criterion for statistical significance. An exploratory mixed-furnishings multivariable linear regression volition be done, with OSTQOL equally the dependent variable with personal demographic characteristics (sexual activity, age and ethnicity) and selected clinical measures as covariables. Study centre volition be included equally a random intercept, and results will be presented with unadjusted and adapted beta coefficients, with associated 95% confidence intervals. Covariables may exist removed if in that location is evidence of multicollinearity or other model fit issues that are predictable with small-scale sample size.
Evaluation three: the experiences of participants who have been randomly allocated to receive BUP-XR or BUP-SL or MET with adjunctive personalised psychosocial intervention over 24 weeks
Procedure and measures
This is a single centre evaluation at the Southward London center, with a target sample of fifteen participants for each allocation (BUP-XR or BUP-SL or MET) to investigate the experience of trial medication and adjunctive personalised psychosocial intervention over 24 weeks. Participants completing the trial endpoint will be approached to consent for a face-to-face, ~30 min interview at the middle. The interview topic guide volition follow the construction of the Adjust. This evaluation volition use a repeated measures set up of clinical measures from the trial (table 1).
The primary result measure will exist reported every 2 weeks and at the baseline visit using a Timeline Followback interview: self-reported opioid, cocaine and benzodiazepine use will exist validated with a UDS. A Psychosocial intervention therapy session log will be recorded frequently throughout the trial, including type, format and duration of the therapy received. The number of days enrolled in report handling and psychosocial intervention engagement volition be calculated when the participant reaches the study endpoint. Participants classified every bit 'engaged' will have attended at least 1 psychosocial intervention engagement after the initial formulation.
Analysis
The analysis of the interview transcripts volition follow the aforementioned 4-step process—descriptive, conceptualising, differentiating and externalising—procedure as in evaluations 1 and ii. The Accommodate will guide deductive coding. Difference between treatment groups and groups of engaged and 'non-engaged' participants will be mapped onto constructs of the behavioural model for health service use model during the conceptualisation stage. For the quantitative analysis, measures will exist tabulated by BUP-XR and BUP-SL and MET with differences evaluated using a 5% criterion for statistical significance. An exploratory quantitative analysis of the primary and secondary upshot measures will be reported post-obit the statistical analysis programme for EXPO.
Study condition
This inquiry is ongoing at the time of protocol submission. Recruitment of participants for evaluation 1 has been open since December 2019 and is expected to be completed in December 2022. Information analysis is scheduled to commence in December 2022. Recruitment of participants for evaluation ii has been open since June 2021 and is expected to be completed in December 2022. Data analysis is planned to commence in early 2023. Recruitment of participants for evaluation iii has been open since Dec 2019 and is expected to exist completed in Dec 2022. Data analysis is planned to commence in early 2023.
Ethics and dissemination
The EXPO study protocol, consent forms and research questionnaires were approved by the London-Brighton and Sussex research ideals commission (reference: 19/LO/0483) and the Wellness Research Authorisation (IRAS projection number: 255522). The EXPO trial is registered (EudraCT: 2018-004460-63). Prior to consenting, participants will be provided with a participant information sail; informed written consent will exist obtained for each evaluation in this research and signed by the principal or appointed subinvestigator. The finding will be disseminated through publications in peer-reviewed scientific journals.
Ethics statements
Patient consent for publication
Ethics approving
This report involves human participants and was approved by London-Brighton and Sussex research ethics committeereference number/ID:19/LO/0483Health Inquiry Authority (IRAS projection number: 255522). Participants gave informed consent to participate in the report earlier taking part.
Acknowledgments
This protocol paper represents independent, investigator-initiated research at Male monarch'due south College London and South London & Maudsley NHS Trust, Bangor University and collaborating NHS hospitals: Cumbria, Northumberland, Tyne & Wear NHS Foundation Trust; Birmingham & Solihull Mental Health NHS Foundation Trust; Greater Manchester Mental Health NHS Foundation Trust and Dundee Drug & Alcohol Recovery Service. Kings College London and South London & Maudsley NHS Trust are the joint study sponsors and hold the indemnity insurance policy. The authors wish to thank the members of the written report oversight committees: TSC: Professor Richard Holland, caput of Leicester Medical Schoolhouse and professor of Public Wellness Medicine (Chair); Steve Taylor, programme manager; Public Health England; Martin McCusker, PPI representative; Jenny Bearn, consultant psychiatrist, independent advisor; Rory Grey, senior commissioning officer Principal Care, Substance Misuse & Homeless Health; Lambeth Council and Christopher D'Souza, atomic number 82 commissioner Substance Misuse, Primary Intendance and Homeless Wellness. DMC: Tim Millar, professor of Substance Employ and Addictions, University of Manchester (DMC Chair); Simon Skene, professor of Medical Statistics, director of Surrey Clinical Trials Unit of measurement and Clinical Research Facility (Independent Statistician); Dr John Dunn, consultant in Habit Psychiatry, Camden Specialist Drug Treatment Service (Independent Clinician); Paul Lennon (PPI Representative); April Wareham (PPI representative).
37/4 As A Mixed Number,
Source: https://bmjopen.bmj.com/content/12/10/e067194
Posted by: poorewiced2001.blogspot.com
0 Response to "37/4 As A Mixed Number"
Post a Comment