Private prescribing of controlled opioids in England, 2014-2021: a retrospective observational study.

BACKGROUND: Trends in NHS opioid prescribing have been well published, yet trends in private prescribing of opioids have not been widely established. AIM: To assess trends and geographical variation in controlled opioids prescribed by private prescribers in England. DESIGN AND SETTING: This was a retrospective observational study in English primary health care. METHOD: Data on Schedule 2 and 3 controlled opioids ('controlled opioids') were obtained from the NHS Business Services Authority (BSA) using Freedom of Information (FOI) requests between 1 January 2014 and 30 November 2021. Absolute counts and rates of the number of items dispensed per cumulative number of registered private prescribers were calculated and stratified over time, by opioid type, and geographical region. RESULTS: This study found that 128 341 items of controlled opioids were prescribed by private prescribers in England between January 2014 and November 2021, which decreased by 50% from 23 339 items (4.09 items/prescriber) in 2014 to 11 573 items (1.49 items/prescriber) in 2020. Methadone (36%, n = 46 660) was the most common controlled opioid prescribed privately, followed by morphine (18%, n = 22 543), buprenorphine (16%, n = 20 521), and oxycodone (12%, n = 15 319). Prescriptions were highest in London (74%, n = 94 438), followed by the South-East of England (7%, n = 9237). A proportion of items (n = 462; 0.36%) were prescribed by 'unidentified doctors' where the prescription is not readily attributable to an individual prescriber by the BSA. CONCLUSION: Controlled opioids prescribed by private prescribers in England decreased and were primarily prescribed in London. To ensure patient safety, the monitoring and surveillance of controlled opioids dispensed privately should continue and items linked to 'unidentified doctors' should be addressed further.

Preventable deaths involving opioids in England and Wales, 2013-2022: a systematic case series of coroners' reports.

BACKGROUND: Opioid deaths have increased in England and Wales. Coroners' Prevention of Future Deaths reports (PFDs) provide important insights that may enable safer use and avert harms, yet reports implicating opioids have not been synthesized. We aimed to identify opioid-related PFDs and explore coroners' concerns to prevent future deaths. METHODS: In this systematic case series, we screened 3897 coronial PFDs dated between 01 July 2013 and 23 February 2022, obtained by web scraping the UK's Courts and Tribunals Judiciary website. PFDs were included when an opioid was implicated in the death. Included PFDs were descriptively analysed, and content analysis was used to assess concerns reported by coroners. RESULTS: Opioids were involved in 219 deaths reported in PFDs (5·6% of PFDs), equating to 4418 years of life lost (median 33 years/person). Morphine (29%), methadone (23%) and diamorphine (16%) were the most common implicated opioids. Coroners most frequently raised concerns regarding systems and protocols (52%) or safety issues (15%). These concerns were most often addressed to National Health Service (NHS) organizations (51%), but response rates were low overall (47%). CONCLUSIONS: Opioids could be used more safely if coroners' concerns in PFDs were addressed by national organizations such as NHS bodies, government agencies and policymakers, as well as individual prescribing clinicians.

Recognition of Coroners' Concerns to Prevent Future Deaths from Medicines: A Systematic Review.

BACKGROUND: Coroners, who hold inquests to determine the causes of unnatural deaths in England and Wales, having recognised factors that could cause other deaths, are legally obliged to signal concerns by sending 'Reports to Prevent Future Deaths' (PFDs) to interested persons. We aimed to establish whether Coroners' concerns about medications are widely recognised. METHODS: We searched MEDLINE, Embase and Web of Science up to 30 November, 2022 for publications linking PFDs and medications using a combination of search terms "coroner*", "inquest*", "medicine*", "medication*" and "prevent*". We also searched the BMJ, a UK journal that carries news items; and the databases Nexis Advance and News On the Web for reports in national newspapers between 2013 and 2022, using the search terms ("regulation 28" OR "prevent future deaths" OR "prevention of future deaths") AND "coroner". We recorded the number of publications, as well as their citations in Google Scholar at 23 May, 2023. RESULTS: Only 11 published papers on medicines referenced UK PFDs, nine of which were from our group. The BMJ carried 23 articles mentioning PFDs, five related to medicines. Of 139 PFDs (out of over 4000) mentioned in national newspapers, only nine related to medicines. CONCLUSIONS: The PFDs related to medicines are not widely referred to in medical journals or UK national newspapers. By contrast, the Australian and New Zealand National Coronial Information System has contributed cases to 206 publications cited in PubMed, of which 139 are related to medicines. Our search suggests that information from English and Welsh Coroners' PFDs is under-recognised, even though it should inform public health. The results of inquiries by Coroners and medical examiners worldwide into potentially preventable deaths involving medicines should be used to strengthen the safety of medicines.

Is England facing an opioid epidemic?

The opioid crisis in the United States (US) is one of the most high-profile public health scandals of the 21st century with millions of people unknowingly becoming dependent on opioids. The United Kingdom (UK) had the world's highest rate of opioid consumption in 2019, and opiate-related drug poisoning deaths have increased by 388% since 1993 in England and Wales. This article explores the epidemiological definitions of public health emergencies and epidemics in the context of opioid use, misuse, and mortality in England, to establish whether England is facing an opioid crisis.

Preventable Deaths Involving Medicines: A Systematic Case Series of Coroners' Reports 2013-22.

INTRODUCTION: Medicines cause over 1700 preventable deaths annually in England. Coroners' Prevention of Future Death reports (PFDs) are produced in response to preventable deaths to facilitate change. The information in PFDs may help reduce medicine-related preventable deaths. OBJECTIVES: We aimed to identify medicine-related deaths in coroners' reports and to explore concerns to prevent future deaths. METHODS: We carried out a retrospective case series of PFDs across England and Wales, dated between 1 July, 2013 and 23 February, 2022, collected from the UK's Courts and Tribunals Judiciary website using web scraping, generating an openly available database: https://preventabledeathstracker.net/ . We used descriptive techniques and content analysis to assess the main outcome criteria: the proportion of PFDs in which coroners reported that a therapeutic medicine or drug of abuse had caused or contributed to a death; the characteristics of included PFDs; coroners' concerns; the recipients of PFDs; and the timeliness of their responses. RESULTS: There were 704 PFDs (18%; 716 deaths) that involved medicines, representing an estimated 19,740 years of life lost (average of 50 years lost per death). Opioids (22%), antidepressants (9.7%), and hypnotics (9.2%) were the most common drugs involved. Coroners expressed 1249 concerns, primarily around the major themes of patient safety (29%) and communication (26%), including minor themes of failures of monitoring (10%) and poor communication between organizations (7.5%). Most expected responses to PFDs (51%; 630/1245) were not reported on the UK's Courts and Tribunals Judiciary website. CONCLUSIONS: One in five coroner-reported preventable deaths involved medicines. Addressing coroners' concerns, including problems with patient safety and communication, should reduce harms from medicines. Despite concerns being raised repeatedly, half of the PFD recipients failed to respond, suggesting that lessons are not generally learned. The rich information in PFDs should be used to foster a learning environment in clinical practice that may help reduce preventable deaths. CLINICAL TRIAL REGISTRATION: https://doi.org/10.17605/OSF.IO/TX3CS .

Lessons from web scraping coroners' Prevention of Future Deaths reports.

In England and Wales, coroners are required to write Prevention of Future Deaths reports when a death is deemed preventable so that action is taken to avert similar deaths. Since July 2013, Prevention of Future Deaths reports have been openly available via the Courts and Tribunals Judiciary website (https://www.judiciary.uk/prevention-of-future-death-reports/). However, their presentation to date have been insufficient to identify trends and learn lessons. We designed a web scraper to create the Preventable Deaths Tracker (https://preventabledeathstracker.net/). On 22 June 2022, 4001 PFDs were scraped, analysed, and compared to the Office of National Statistics' preventable mortality statistics. This commentary summarises the key findings and offers recommendations to improve the Prevention of Future Deaths system so lessons can be learnt to avert preventable deaths.

Registration of health and medical research.

Registration of health and medical research is an effective way of improving the transparency and credibility of evidence. Registration involves pre-specifying the research objectives, design, methods and analytic plan on a publicly accessible repository before conducting the study. Registration can reduce bias and improve the transparency and credibility of research findings. Registration is mandated for clinical trials, but it is also relevant to systematic reviews, observational and preclinical experimental research. This paper describes how researchers can register their research and outlines possible barriers and challenges in doing so. Widespread adoption of research registration can reduce research waste and improve evidence-informed clinical and policy decision making.

Sharing study materials in health and medical research.

Making study materials available allows for a more comprehensive understanding of the scientific literature. Sharing can take many forms and include a wide variety of outputs including code and data. Biomedical research can benefit from increased transparency but faces unique challenges for sharing, for instance, confidentiality concerns around participants' medical data. Both general and specialised repositories exist to aid in sharing most study materials. Sharing may also require skills and resources to ensure that it is done safely and effectively. Educating researchers on how to best share their materials, and properly rewarding these practices, requires action from a variety of stakeholders including journals, funders and research institutions.

Open science and conflict of interest policies of medical and health sciences journals before and during the COVID-19 pandemic: A repeat cross-sectional study: Open science policies of medical journals.

Objectives: To audit the transparent and open science standards of health and medical sciences journal policies and explore the impact of the COVID-19 pandemic. Design: Repeat cross-sectional study. Setting: 19 journals listed in Google Scholar's Top Publications for health and medical sciences. Participants: Blood, Cell, Circulation, European Heart Journal, Gastroenterology, Journal of Clinical Oncology, Journal of the American College of Cardiology, Nature Genetics, Nature Medicine, Nature Neuroscience, Neuron, PLoS ONE, Proceedings of the National Academy of Sciences, Science Translational Medicine, The British Medical Journal, The Journal of the American Medical Association, The Lancet, The Lancet Oncology, and The New England Journal of Medicine. Main outcome measures: We used the Transparency and Openness Promotion (TOP) guideline and the International Committee of Medical Journal Editors (ICMJE) requirements for disclosing conflicts of interest (COIs) to evaluate journals standards. Results: TOP scores slightly improved during the COVID-19 pandemic, from a median of 5 (IQR: 2-12.5) out of a possible 24 points in February 2020 to 7 (IQR: 4-12) in May 2021, but overall, scores were very low at both time points. Journal policies scored highest for their adherence to data transparency and scored lowest for preregistration of study protocols and analysis plans and the submission of replication studies. Most journals fulfilled all ICMJE provisions for reporting COIs before (84%; n = 16) and during (95%; n = 18) the COVID-19 pandemic. Conclusions: The COVID-19 pandemic has highlighted the importance of practising open science. However, requirements for open science practices in audited policies were overall low, which may impede progress in health and medical research. As key stakeholders in disseminating research, journals should promote a research culture of greater transparency and more robust open science practices.

Global, regional, and national consumption of controlled opioids: a cross-sectional study of 214 countries and non-metropolitan territories.

INTRODUCTION: The consumption of opioids has increased globally since the 1990s. Previous studies of global opioid consumption have concentrated on morphine alone or a subset of opioids, with a focus on cancer pain and palliative care. In this study, we have determined the global, regional, and national consumption of all controlled opioids, including anaesthetics, analgesics, antidiarrheals, opioid substitution therapies, and cough suppressants. METHODS: We conducted a cross-sectional study using data from the International Narcotics Control Board (INCB). We calculated mean opioid consumption (mg/person) globally, regionally, and nationally for 2015-2017, where consumption refers to the total amount of controlled opioids distributed for medical purposes and excludes recreational use. We ranked countries by total consumption and quantified the types of opioids consumed globally. RESULTS: Between 2015 and 2017, 90% of the world's population consumed only 11% of controlled opioids. An average of 32 mg/person was consumed annually, but this was not equally distributed across the world. Consumption was the highest in Germany (480 mg/person), followed by Iceland (428 mg/person), the United States (398 mg/person) and Canada (333 mg/person). Oxycodone (35%) was the most heavily consumed controlled opioid globally, followed by morphine (15.9%), methadone (15.8%) and tilidine (14%). CONCLUSION: Large disparities persist in most of the world in accessing essential opioid medicines. Consumption patterns should continue to be monitored, and collaborative strategies should be developed to promote access and the appropriate prescribing of opioids in all countries and non-metropolitan territories.

Sales of Over-the-Counter Products Containing Codeine in 31 Countries, 2013-2019: A Retrospective Observational Study.

INTRODUCTION: Opioid prescribing trends have been investigated in many countries. However, the patterns of over-the-counter purchases of opioids without a prescription, such as codeine combinations, are mostly unknown. OBJECTIVE: We aimed to assess national sales and expenditure trends of over-the-counter codeine-containing products purchased in countries with available data over 6 years. METHODS: We conducted a retrospective observational study using electronic point-of-sale data from the human data science company, IQVIA, for countries that had such data, including Argentina, Belgium, Brazil, Bulgaria, Canada, Croatia, Estonia, Finland, France, Germany, Greece, Ireland, Italy, Japan, Latvia, Lithuania, Mexico, the Netherlands, Poland, Portugal, Romania, Russia, Serbia, Slovakia, Slovenia, South Africa, Spain, Switzerland, Thailand, the UK, and the USA. We calculated annual mean sales (dosage units/1000 population) and public expenditure (£/1000 population) for each country between April 2013 and March 2019 and adjusted for data coverage reported by IQVIA. We quantified changes over time and the types of products sold. RESULTS: In total, 31.5 billion dosage units (adjusted: 42.8 billion dosage units) of codeine, costing £2.55 billion (adjusted: £3.68 billion), were sold over the counter in 31 countries between April 2013 and March 2019. Total adjusted sales increased by 11% (from 3911 dosage units/1000 population in 2013 to 4358 in 2019) and adjusted public expenditure increased by 72% (from £263/1000 in 2013 to £451/1000 in 2019). Sales were not equally distributed; South Africa sold the most (36 mean dosage units/person), followed by Ireland (30 mean dosage units/person), France (20 mean dosage units/person), the UK (17.2 mean dosage units/person), and Latvia (16.8 mean dosage units/person). Types of products (n = 569) and formulations (n = 12) sold varied. CONCLUSION: In many parts of the world, substantial numbers of people may be purchasing and consuming codeine in over-the-counter products. Clinicians should ask patients about their use of over-the-counter products, and public health measures are required to improve the collection of sales data and the safety of such products. STUDY PROTOCOL PRE-REGISTRATION: https://osf.io/ay4mc . The pre-print version of this work is available on medRxiv: https://doi.org/10.1101/2021.04.21.21255888 .

Deaths from cardiovascular disease involving anticoagulants: a systematic synthesis of coroners' case reports.

BACKGROUND: The global burden of cardiovascular disease (CVD) is forecast to increase, and anticoagulants will remain important medicines for its management. Coroners' Prevention of Future Death reports (PFDs) provide valuable insights that may enable safer and more effective use of these agents. AIM: To identify CVD-related PFDs involving anticoagulants. DESIGN & SETTING: Case series of coronial reports in England and Wales between 2013 and 2019. METHOD: A total of 3037 PFDs were screened for eligibility. PFDs were included where CVD and an anticoagulant caused or contributed to the death. Included cases were descriptively analysed and content analysis was used to assess concerns raised by coroners and who had responded to them. RESULTS: The study identified 113 CVD-related PFDs involving anticoagulants. Warfarin (36%, n = 41), enoxaparin (11%, n = 12), and rivaroxaban (11%, n = 12) were the most common anticoagulants reported. Concerns most frequently raised by coroners included poor systems (31%), poor communication (25%), and failures to keep accurate medical records (25%). These concerns were most often directed to NHS trusts (29%), hospitals (10%), and general practices (8%). Nearly two-thirds (60%) of PFDs had not received responses from such organisations, which are mandatory under regulation 28 of the Coroners' (Investigations) Regulations 2013. A publicly available tool has been created by the authors (https://preventabledeathstracker.net), which displays coroners' reports in England and Wales to streamline access, and identify important lessons to prevent future deaths. CONCLUSION: National organisations, healthcare professionals, and prescribers should take actions to address the concerns of coroners in PFDs to improve the safe use of anticoagulants in patients with CVD.

Preventable deaths from SARS-CoV-2 in England and Wales: a systematic case series of coroners' reports during the COVID-19 pandemic.

OBJECTIVES: To examine coroners' Prevention of Future Deaths (PFDs) reports to identify deaths involving SARS-CoV-2 that coroners deemed preventable. DESIGN: Consecutive case series. SETTING: England and Wales. PARTICIPANTS: Patients reported in 510 PFDs dated between 01 January 2020 and 28 June 2021, collected from the UK's Courts and Tribunals Judiciary website using web scraping to create an openly available database: https://preventabledeathstrackernet/. MAIN OUTCOME MEASURES: Concerns reported by coroners. RESULTS: SARS-CoV-2 was involved in 23 deaths reported by coroners in PFDs. Twelve deaths were indirectly related to the COVID-19 pandemic, defined as those that were not medically caused by SARS-CoV-2, but were associated with mitigation measures. In 11 cases, the coroner explicitly reported that COVID-19 had directly caused death. There was geographical variation in the reporting of PFDs; most (39%) were written by coroners in the North West of England. The coroners raised 56 concerns, problems in communication being the most common (30%), followed by failure to follow protocols (23%). Organisations in the National Health Service were sent the most PFDs (51%), followed by the government (26%), but responses to PFDs by these organisations were poor. CONCLUSIONS: PFDs contain a rich source of information on preventable deaths that has previously been difficult to examine systematically. Our openly available tool (https://preventabledeathstracker.net/) streamlines this process and has identified many concerns raised by coroners that should be addressed during the government's inquiry into the handling of the COVID-19 pandemic, so that mistakes made are less likely to be repeated. STUDY PROTOCOL PREREGISTRATION: https://osf.io/bfypc/.

The impact of proposed regulatory changes and rescheduling on low-dose codeine purchasing in Canada: a time-series analysis.

BACKGROUND: Low-dose codeine products can be purchased without a prescription in most of Canada. We explored trends in the purchasing of these products across the Canadian provinces from 2014 to 2019, evaluating the impact of Health Canada's 2016 announcement of a proposed regulatory change and the 2017 opening of a 60-day public comment period, as well as the impact of Manitoba's 2016 policy change requiring a prescription for the purchase of all codeine products in that province. METHODS: We evaluated population-adjusted monthly purchasing of codeine products from January 2014 to October 2019 using the IQVIA Canadian Drug Store and Hospital Purchases Audit database, stratified by province and over-the-counter (OTC) status. The primary outcomes were change in the monthly volume of low-dose codeine purchased after the 2016 federal regulatory proposal and the 2017 period of public comment across the provinces. Our secondary analysis was the impact of Manitoba's policy change in February 2016 requiring a prescription for low-dose codeine. We conducted a time-series analysis using interventional autoregressive integrated moving average models. RESULTS: Over the study period, 24 120 kg of codeine (3.025 billion units) and 937 867 kg of acetaminophen were sold as OTC, low-dose codeine products across the Canadian provinces. Health Canada's 2016 announcement did not significantly affect OTC codeine purchasing (p = 0.57). The initiation of a 60-day public comment period was associated with a roughly 44% decrease in OTC codeine purchasing (p = 0.03). In Manitoba, purchasing of the same codeine formulations decreased after rescheduling in February 2016 (p < 0.001). We observed no significant change in the rate of purchasing of higher dose codeine formulations in response to scheduling changes in Manitoba (p = 0.22). INTERPRETATION: Although Health Canada's 2016 announcement of a proposed regulatory change did not appear to have an effect on OTC codeine purchasing nationally, the 60-day comment period was associated with a decrease in purchasing. Further, Manitoba's 2016 policy change was associated with a significant and sustained decrease in the overall volume of codeine purchased. Given the potential risks of codeine dependence and acetaminophen toxicity with these products, a national rescheduling strategy should be considered.