Impact of the COVID-19 pandemic on opioid agonist treatment in Ireland: Protocol for an interrupted time series analysis

Gráinne Cousins; Louise Durand; Fiona Boland; Norma Harnedy; Íde Delargy; Mike Scully; Margaret Bourke; William Ebbitt; María Otero Vázquez; Eamon Keenan

doi:10.12688/hrbopenres.13341.1

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Study Protocol

Impact of the COVID-19 pandemic on opioid agonist treatment in Ireland: Protocol for an interrupted time series analysis

[version 1; peer review: 1 approved, 1 approved with reservations]

Gráinne Cousins ¹, Louise Durand¹, Fiona Boland², [...] Norma Harnedy³, Íde Delargy⁴, Mike Scully⁵, Margaret Bourke⁶, William Ebbitt⁵, María Otero Vázquez⁷, Eamon Keenan⁸

Gráinne Cousins ¹, Louise Durand¹, [...] Fiona Boland², Norma Harnedy³, Íde Delargy⁴, Mike Scully⁵, Margaret Bourke⁶, William Ebbitt⁵, María Otero Vázquez⁷, Eamon Keenan⁸

PUBLISHED 19 Aug 2021

Author details Author details

¹ School of Pharmacy and Biomolecular Sciences, Royal College of Surgeons in Ireland, Dublin, Dublin 2, Ireland
² Data Science Centre and Department of General practice, Royal College of Surgeons in Ireland, Dublin 2, Ireland
³ Addiction Services, Health Service Executive (HSE), PO Box 486, Corporate House, Mungret Street, Limerick, Ireland
⁴ Irish College of General Practitioners, Lincoln Place, Dublin 2, Ireland
⁵ National Drug Treatment Centre, Health Service Executive, 30/31 Pearse street, Dublin 2, Ireland
⁶ Addiction Services, Health Services Executive, Castle Street, Dublin 2, Ireland
⁷ UISCE, 8 Cabra road, Dublin 7, Ireland
⁸ National Social Inclusion Office, Health Services Executive Primary Care Division, Dublin 20, Ireland

Gráinne Cousins
Roles: Conceptualization, Formal Analysis, Funding Acquisition, Investigation, Methodology, Project Administration, Supervision, Validation, Visualization, Writing – Original Draft Preparation, Writing – Review & Editing

Louise Durand
Roles: Conceptualization, Formal Analysis, Investigation, Methodology, Project Administration, Validation, Writing – Original Draft Preparation, Writing – Review & Editing

Fiona Boland
Roles: Conceptualization, Formal Analysis, Funding Acquisition, Investigation, Methodology, Writing – Review & Editing

Norma Harnedy
Roles: Funding Acquisition, Writing – Review & Editing

Íde Delargy
Roles: Funding Acquisition, Writing – Review & Editing

Mike Scully
Roles: Funding Acquisition, Writing – Review & Editing

Margaret Bourke
Roles: Funding Acquisition, Writing – Review & Editing

William Ebbitt
Roles: Data Curation, Funding Acquisition, Writing – Review & Editing

María Otero Vázquez
Roles: Funding Acquisition, Writing – Review & Editing

Eamon Keenan
Roles: Conceptualization, Funding Acquisition, Investigation, Methodology, Project Administration, Supervision, Writing – Review & Editing

OPEN PEER REVIEW

REVIEWER STATUS

Abstract

While opioid agonist treatment (OAT) is the most effective treatment for opioid dependence, it is heavily dependent on regular face-to-face healthcare delivery placing both clients and treatment providers at risk of COVID-19. Following the emergence of COVID-19, policies were rapidly changed in Ireland, with the introduction of national contingency guidelines by the HSE National Social Inclusion Office, beginning in March 2020 to ensure rapid and uninterrupted access to OAT while balancing efforts to mitigate COVID-19 risk. This study aims to assess the impact of the national contingency guidelines, on the quality of OAT care delivered in Ireland.

An interrupted time series analysis will be conducted using anonymised aggregated level data obtained from the Central Treatment List (CTL), the national register of people receiving OAT, administered by the National Drug Treatment Centre Board on behalf of the HSE. Separate segmented regressions will be conducted to estimate the impact of the national contingency guidelines on the following outcomes: (1) number of patients in treatment; (2) number of patients starting OAT; (3) average waiting time for treatment; (4) number of people on waiting list; (5) number of patients dropping out of treatment. The study period will be divided into pre-(March 2019 to February 2020) and post- intervention (April 2020 to March 2021) segments. Immediate (change in level) and longer-term impacts (change in slope) of changes to provision of OAT in each of the outcomes will be investigated. Regression coefficients (β) and 95% confidence intervals (CIs) will be reported.

Keywords

COVID-19, opioid agonist treatment, interrupted time series, addiction services, drug policy, public health, substance use disorder, harm reduction

Corresponding author: Gráinne Cousins

Competing interests: No competing interests were disclosed.

Grant information: Health Research Board under the Research Collaborative in Quality and Patient Safety (RCQPS), a collaborative initiative between the Health Research Board, the Health Service Executive, National Quality Improvement Team and the Royal College of Physicians of Ireland [RCQPS-2020-016].
The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Copyright: © 2021 Cousins G et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

How to cite: Cousins G, Durand L, Boland F et al. Impact of the COVID-19 pandemic on opioid agonist treatment in Ireland: Protocol for an interrupted time series analysis [version 1; peer review: 1 approved, 1 approved with reservations]. HRB Open Res 2021, 4:91 (https://doi.org/10.12688/hrbopenres.13341.1) First published: 19 Aug 2021, 4:91 (https://doi.org/10.12688/hrbopenres.13341.1) Latest published: 19 Aug 2021, 4:91 (https://doi.org/10.12688/hrbopenres.13341.1)

Introduction

Although COVID-19 presents a significant threat to everyone, people with opioid dependence are particularly vulnerable to the disease and its sequelae, as they have a higher burden of co-existing health problems¹, with many living in areas of social deprivation, with poor-quality housing or homelessness². Opioid agonist treatment (OAT), using methadone or buprenorphine, is the first line treatment for opioid dependence, as it has been shown to be safe and effective in suppressing illicit opioid use^3,4, improving mental and physical well-being⁵, and reducing mortality⁶. In fact, a recent systematic review identified that risk of all-cause mortality, overdose, suicide, alcohol-related, cancer and cardiovascular-related mortality, were significantly lower for people with opioid dependence on OAT compared to those not on OAT⁶. The authors highlighted the importance of increasing access to OAT and maintaining people on OAT who are in critical need of treatment to reduce their mortality risk⁶.

Methadone is the most common form of OAT in Ireland, and is available free of charge to all persons undergoing OAT for opioid dependence⁷. In 1998, the Misuse of Drugs Regulations were introduced in Ireland, providing the Methadone Treatment Protocol, a model of care which formed the basis for the clinical governance and quality of delivery of drug treatment in Ireland. This coincided with the establishment of a national treatment register, the Central Treatment List (CTL). The 1998 Regulations were updated in 2017 to provide for OAT using buprenorphine. All patients in receipt of OAT for opioid dependence are registered on the CTL, with each person linked to one specific prescriber and a single dispensing site. OAT is provided in specialist outpatient addiction clinics or primary care. There are an estimated 18,988 people with opioid dependence in Ireland⁸, with 10,580 recorded as being in receipt of OAT in 2019.

Acting on the recommendations of the 2010 external review of the Methadone Treatment Protocol⁹, detailed clinical guidelines for OAT were developed in 2016, to standardise and improve the quality and safety of OAT care¹⁰. The emergence of COVID-19 presented significant challenges to the provision of OAT services within the existing regulations and clinical guidelines, as OAT is heavily dependent on regular face-to-face health care delivery. At the beginning of the pandemic, there were real concerns that disruption to care, particularly access to OAT and other prescribed medication, would have detrimental consequences for people in treatment. Furthermore, it was anticipated that many people would seek treatment during COVID-19 due to disruptions to the supply of illicit opioids. This led to a rapid and coordinated response, to mitigate the spread of COVID-19, while ensuring continued and safe access to OAT, across multiple sectors of the Irish Health and Social Care system. Multiple bodies serving different but overlapping functions came together to facilitate rapid decision making in a highly regulated environment, resulting in the introduction of a suite of national contingency guidelines by the Health Service Executive (HSE) starting from March 2020. These contingency guidelines supported accelerated access to OAT for people not already in treatment, including increased access to buprenorphine, e-consultations and transferring patients, where possible from supervised consumption to take-home doses, with the possibility of up to 14-days’ supply. They also provided for e-prescriptions, home delivery of prescription medications, including methadone or buprenorphine, and needle exchange for those self-isolating. The contingency guidelines also recommended increased prescribing of naloxone, an opioid reversal agent that may mitigate the risks of fatal overdose from opioids, and advice in relation to the management of alcohol and benzodiazepine dependency. Provisions were also made to support people in residential facilities, including isolation hubs and homeless accommodation¹¹.

Rapid access to OAT is an important marker of quality of patient care, and COVID-19 has perhaps created an opportunity to increase the number of people entering treatment in Ireland. However, growing evidence suggests that the risk of mortality following dropout from OAT is high^6,7,12; therefore, it is also important to review the level of dropout from OAT, alongside numbers in treatment. The aim of this study is to evaluate the impact of the national contingency guidelines introduced from March 2020 on number of patients on OAT, numbers initiating OAT, numbers on waiting list, waiting times, and patient dropout using an interrupted time series (ITS) design. ITS is a strong quasi-experimental research design to evaluate the impacts of health policy interventions where randomization is not possible¹³.

Protocol

Study design and data source

Interrupted time series analyses will be conducted using anonymised aggregated level data obtained from the Central Treatment List (CTL), the national register of people receiving OAT, administered by the National Drug Treatment Centre Board on behalf of the HSE. People are registered on the CTL while waiting for a treatment place, and once in treatment clinicians have a statutory obligation to report treatment initiation details to the CTL. Clients’ treatment status on the CTL remains active for up to four weeks from their first day of non-attendance with their treatment provider. During this time, attempts are made to contact the client to encourage them to return to treatment. If no contact is made, and the client does not attend for treatment for four consecutive weeks, an exit form is completed on the CTL. As a mandatory national register, aggregated numbers from the CTL are nationally representative. The RCSI Research Ethics Committee approved this study (REC202009008). Data will be de-identified, aggregated data, and therefore no consent is required for their use. This work will be conducted following the Strobe Standardised Reporting Guidelines for Cross-Sectional Studies, as this study involves a repeated cross-sectional analysis¹⁴.

Inclusion criteria

We will include data recorded on the CTL between March 2019 and March 2021. This time-period was chosen because it includes the period when the national contingency guidelines were implemented (March 2020), and contains a sufficient run-in phase before the changes were introduced (March 2019 to February 2020), as well as a 12-month follow-up phase to examine the immediate and short-term effects of the contingency guidelines.

Outcome measures

1. Number of patients receiving OAT, defined as the total number of patients in treatment on the last day of each month.
2. Number of patients starting OAT, defined as the number of patients who were initiated on OAT each month. This includes patients who were initiated on OAT for the first time ever and those who were re-initiated following a period of >28 days out of treatment.
3. Average waiting time for treatment, defined as the average time in days between registering on the national waiting list and induction on OAT each month.
4. Number of people on national waiting list on the last day of each month.
5. Number of patients dropping out of treatment, defined as >4 weeks out of treatment.

Statistical analysis

The observation period is March 2019 to March 2021, with data points defined by calendar month. As the contingency measures were introduced from March 2020, March 2020 will be removed from the ITS analysis. A graphical exploratory approach will be undertaken to identify potential outliers, underlying trends and patterns, and any lagged effect of the intervention that may need to be accounted for in the models. Given that we are seeking to determine the immediate and short-term impacts of the changes introduced, we have a relatively low number of data points (12 pre- and 12 post-change); therefore, we will use a priori segmented regressions to fit the data¹³. We will conduct separate segmented regression models (March 2019 – February 2020 compared to April 2020 – March 2021) for each of the five outcomes, examining the change in monthly level and slope, and present regression coefficients (β) and 95% confidence intervals (CIs). Autocorrelation and partial autocorrelation function plots will be visually inspected, and the Durbin Watson statistic will be used to identify the presence of residual autocorrelation. In the presence of autocorrelation in the model residuals, a generalised least-squares transformation (Prais-Winsten) will be applied to the models. A significance level of α=0.05 will be assumed. Sub-group analyses by sex, age, location and OAT drug (methadone or buprenorphine) will be performed where possible. Data analyses will be performed using Stata/SE v16.0.

Dissemination

Study findings will be submitted for publication in a peer-reviewed journal and to relevant national and international conferences. Our study findings will also be disseminated via a research brief or webinar to relevant stakeholders including HSE Social Inclusion Commissioning Team; Department of Health National Oversight Committee for National Drug and Alcohol Strategy; HSE National Quality Improvement Team; Irish College of General Practitioners; Irish Institute of Pharmacy; College of Psychiatrists of Ireland; and the European Monitoring Centre for Drugs and Drug Addiction. We will also collaborate with UISCE, the national advocacy service for people who use drugs (PWUD), to create a special edition of our research findings in their magazine, which is disseminated nationally to all services where PWUD attend. Findings will also be disseminated through the use of social media such as Twitter.

Study status

Anonymised aggregated level data has been obtained from the Central Treatment List (CTL).

Discussion

The rapid and coordinated response to mitigate the spread of COVID-19, while ensuring continued and safe access to OAT in Ireland, highlights many bright spots of excellent practice across multiple sectors of the Irish Health and Social Care system during a time of crisis. The Programme for Government 2020 has stressed the need to retain many of the contingency measures introduced, to ensure shorter waiting times and reduced risk of overdose. However, questions remain: how feasible is it to continue with all the changes which were implemented at this time of crisis; is it appropriate or indeed safe to continue with all changes; are there any unintended consequences? The HSE National Social Inclusion Office, who coordinates addiction services, along with General Practitioners, Community Pharmacists, and other key workers in addiction services, now face the challenge of optimising available resources while ensuring continued and safe access to OAT, as we learn to live with COVID-19. This project will highlight the impact of the changes introduced during the pandemic on key process and client outcomes.

Data availability

No data are associated with this article.

Faculty Opinions recommended

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VERSION 1 PUBLISHED 19 Aug 2021