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Hire Dr. Raymond C.

United Kingdom

Statistician and researcher. Experimental design. Pharmacovigilance. Adverse events. Bayesian methods. Causal analyses.

Profile Summary

I am a statistician and statistical researcher. I am currently employed to provide advanced statistical analyses (Bayesian statistics, causal approaches) in epidemiological studies. Part of my role is to provide help to non-statisticians with experimental design and power calculations. My research interests are pharmacovigilance and safety in clinical trials (particularly the detection of adverse events), Bayesian hierarchical models, Markov Chain Monte Carlo methods, and theoretical statistics. In addition I have many years (20+) programming experience (C/C++/shell/perl/R).

Subject Matter Expertise

• ★ Applied Statistics
• ☆ Medical Statistics
• ☆ Epidemiology

Services

• Writing
• Research
• Consulting
• Data & AI
• Product Development

Writing Clinical Trial Documentation, Technical Writing

Research Fact Checking, Gray Literature Search, Systematic Literature Review, Secondary Data Collection

Consulting Scientific and Technical Consulting

Data & AI Statistical Analysis, Algorithm Design-Non ML, Data Visualization

Product Development Formulation

Work Experience

Queen's University Belfast

- Present

Academic, Lecturer, Lecturer

University of the West of Scotland

June 2023 - Present

Queen's University Belfast

January 2022 - Present

Research Fellow

Queen's University Belfast

January 2021 - June 2023

University of Strathclyde

- December 2021

Education

University of Strathclyde

- December 2021

PhD (Department of Mathematics and Statistics)

University of Strathclyde

2013 - 2017

Certifications

• Certification details not provided.

Publications

JOURNAL ARTICLE

Raymond Carragher, Grace R Ings, Gavin Baker, Jeni Rosborough, Dorothy B Johnston, Rajeev Shah, Iain Cameron, Ciaran O'Neill, Paul J Kelly, Gerard McVeigh, et al. (2023). Trends in pathology diagnoses during 10 years of a colorectal cancer screening programme . Histopathology.

Heterogeneity after harmonisation @article{cba26e6061814215b95306666388d65e, title = "Heterogeneity after harmonisation: a retrospective cohort study of bleeding and stroke risk after the introduction of direct oral anticoagulants in four Western European countries", abstract = "PURPOSE: Database heterogeneity can impact effect estimates. Harmonisation provided by common protocols and common data models (CDMs) can increase the validity of pharmacoepidemiologic research. In a case study measuring the changes in the safety and effectiveness of stroke prevention therapy after the introduction of direct oral anticoagulants (DOACs), we performed an international comparison.METHODS: Using data from Stockholm, Denmark, Scotland and Norway, harmonised with a common protocol and CDM, two calendar-based cohorts were created: 2012 and 2017. Patients with a diagnosis code of atrial fibrillation 5 years preceding the 1-year cohort window were included. DOAC, vitamin K antagonist and aspirin treatment were assessed in the 6 months prior to the start of each year while strokes and bleeds were assessed during the year. A Poisson regression generated incidence rate ratios (IRRs) to compare outcomes from 2017 to 2012 adjusted for changes in individual-level baseline characteristics.RESULTS: In 280 359 patients in the 2012 cohort and 356 779 in the 2017 cohort, treatment with OACs increased on average from 45% to 65%, while treatment with aspirin decreased from 30% to 10%. In all countries except Scotland, there were decreases in the risk of stroke and no changes in bleeding risk, after adjustment for changes in baseline characteristics. In Scotland, major bleeding (IRR 1.09, 95% confidence interval [CI] [1.00; 1.18]) and intracranial haemorrhage (IRR 1.31, 95% CI [1.13; 1.52]) increased from 2012 to 2017.CONCLUSIONS: Stroke prevention therapy improved from 2012 to 2017 with a corresponding reduction in stroke risk without increasing the risk of bleeding in all countries, except Scotland. The heterogeneity that remains after methodological harmonisation can be informative of the underlying population and database.", keywords = "anti-coagulants, bleeding, hterogeneity, multi-database, stroke, utilisation", author = "Komen, {J. J.} and Hunt, {N. B.} and A. Potteg{\aa}rd and P. Hjemdahl and B. Wettermark and M. Olesen and M. Bennie and T. Mueller and R. Carragher and {\O}. Karlstad and Kjerpeseth, {L. J.} and Klungel, {O. H.} and T. Forslund", year = "2023", month = jun, day = "6", doi = "10.1002/pds.5650", language = "English", journal = "Pharmacoepidemiology and drug safety", issn = "1053-8569", publisher = "John Wiley and Sons Ltd", } . Pharmacoepidemiology and drug safety.

The impact of the COVID-19 pandemic on cardiovascular disease prevention and management @article{fd83723c5b034c1d907df61e714c4076, title = "The impact of the COVID-19 pandemic on cardiovascular disease prevention and management", abstract = "How the Coronavirus Disease 2019 (COVID-19) pandemic has affected prevention and management of cardiovascular disease (CVD) is not fully understood. In this study, we used medication data as a proxy for CVD management using routinely collected, de-identified, individual-level data comprising 1.32 billion records of community-dispensed CVD medications from England, Scotland and Wales between April 2018 and July 2021. Here we describe monthly counts of prevalent and incident medications dispensed, as well as percentage changes compared to the previous year, for several CVD-related indications, focusing on hypertension, hypercholesterolemia and diabetes. We observed a decline in the dispensing of antihypertensive medications between March 2020 and July 2021, with 491,306 fewer individuals initiating treatment than expected. This decline was predicted to result in 13,662 additional CVD events, including 2,281 cases of myocardial infarction and 3,474 cases of stroke, should individuals remain untreated over their lifecourse. Incident use of lipid-lowering medications decreased by 16,744 patients per month during the first half of 2021 as compared to 2019. By contrast, incident use of medications to treat type 2 diabetes mellitus, other than insulin, increased by approximately 623 patients per month for the same time period. In light of these results, methods to identify and treat individuals who have missed treatment for CVD risk factors and remain undiagnosed are urgently required to avoid large numbers of excess future CVD events, an indirect impact of the COVID-19 pandemic.", author = "Dale, {Caroline E.} and Rohan Takhar and Raymond Carragher and Michail Katsoulis and Fatemeh Torabi and Stephen Duffield and Seamus Kent and Tanja Mueller and Amanj Kurdi and {Le Anh}, {Thu Nguyen} and Stuart McTaggart and Hoda Abbasizanjani and Sam Hollings and Andrew Scourfield and Lyons, {Ronan A.} and Rowena Griffiths and Jane Lyons and Gareth Davies and Daniel Harris and Alex Handy and Mizani, {Mehrdad A.} and Christopher Tomlinson and Thygesen, {Johan H.} and Mark Ashworth and Spiros Denaxas and Amitava Banerjee and Sterne, {Jonathan A.C.} and Paul Brown and Ian Bullard and Rouven Priedon and Mamas, {Mamas A.} and Ann Slee and Paula Lorgelly and Munir Pirmohamed and Kamlesh Khunti and Morris, {Andrew D.} and Cathie Sudlow and Ashley Akbari and Marion Bennie and Naveed Sattar and Reecha Sofat and {CVD-COVID-UK Consortium}", year = "2023", month = jan, day = "19", doi = "10.1038/s41591-022-02158-7", language = "English", volume = "29", pages = "219--225", journal = "Nature Medicine", issn = "1078-8956", publisher = "Nature Publishing Group", number = "1", } . Nature Medicine.

Raymond Carragher, Caroline E. Dale, Rohan Takhar, Michail Katsoulis, Fatemeh Torabi, Stephen Duffield, Seamus Kent, Tanja Mueller, Amanj Kurdi, Thu Nguyen Le Anh, et al. (2023). The impact of the COVID-19 pandemic on cardiovascular disease prevention and management . Nature Medicine.

The impact of the COVID-19 pandemic on cardiovascular disease prevention and management @article{3a8747aac4de4804b27978c7fb2cc392, title = "The impact of the COVID-19 pandemic on cardiovascular disease prevention and management", abstract = "How the Coronavirus Disease 2019 (COVID-19) pandemic has affected prevention and management of cardiovascular disease (CVD) is not fully understood. In this study, we used medication data as a proxy for CVD management using routinely collected, de-identified, individual-level data comprising 1.32 billion records of community-dispensed CVD medications from England, Scotland and Wales between April 2018 and July 2021. Here we describe monthly counts of prevalent and incident medications dispensed, as well as percentage changes compared to the previous year, for several CVD-related indications, focusing on hypertension, hypercholesterolemia and diabetes. We observed a decline in the dispensing of antihypertensive medications between March 2020 and July 2021, with 491,306 fewer individuals initiating treatment than expected. This decline was predicted to result in 13,662 additional CVD events, including 2,281 cases of myocardial infarction and 3,474 cases of stroke, should individuals remain untreated over their lifecourse. Incident use of lipid-lowering medications decreased by 16,744 patients per month during the first half of 2021 as compared to 2019. By contrast, incident use of medications to treat type 2 diabetes mellitus, other than insulin, increased by approximately 623 patients per month for the same time period. In light of these results, methods to identify and treat individuals who have missed treatment for CVD risk factors and remain undiagnosed are urgently required to avoid large numbers of excess future CVD events, an indirect impact of the COVID-19 pandemic. ", keywords = "COVID-19 - epidemiology, Risk Factors, Hypertension - complications - drug therapy - epidemiology, Humans, Cardiovascular Diseases - epidemiology - prevention & control - diagnosis, Pandemics - prevention & control, Diabetes Mellitus, Type 2 - complications - drug therapy - epidemiology", author = "Dale, {Caroline E} and Rohan Takhar and Raymond Carragher and Michail Katsoulis and Fatemeh Torabi and Stephen Duffield and Seamus Kent and Tanja Mueller and Amanj Kurdi and {Le Anh}, {Thu Nguyen} and Stuart McTaggart and Hoda Abbasizanjani and Sam Hollings and Andrew Scourfield and Lyons, {Ronan A} and Rowena Griffiths and Jane Lyons and Gareth Davies and Daniel Harris and Alex Handy and Mizani, {Mehrdad A} and Christopher Tomlinson and Thygesen, {Johan H} and Mark Ashworth and Spiros Denaxas and Amitava Banerjee and Sterne, {Jonathan A C} and Paul Brown and Ian Bullard and Rouven Priedon and Mamas, {Mamas A} and Ann Slee and Paula Lorgelly and Munir Pirmohamed and Kamlesh Khunti and Morris, {Andrew D} and Cathie Sudlow and Ashley Akbari and Marion Bennie and Naveed Sattar and Reecha Sofat", year = "2023", month = jan, doi = "10.1038/s41591-022-02158-7", language = "English", volume = "29", pages = "219--225", journal = "Nature Medicine", issn = "1078-8956", publisher = "Nature Publishing Group", number = "1", } . Nature Medicine.

Oral anticoagulants in patients with atrial fibrillation at low stroke risk @article{e7e4d7d3a17e4e4f9b5fb94da29b3c87, title = "Oral anticoagulants in patients with atrial fibrillation at low stroke risk: a multicentre observational study", abstract = "Aims: There is currently no consensus on whether atrial fibrillation (AF) patients at low risk for stroke (one non-sex-related CHA2DS2-VASc point) should be treated with an oral anticoagulant. Methods and results: We conducted a multi-country cohort study in Sweden, Denmark, Norway, and Scotland. In total, 59 076 patients diagnosed with AF at low stroke risk were included. We assessed the rates of stroke or major bleeding during treatment with a non-vitamin K antagonist oral anticoagulant (NOAC), a vitamin K antagonist (VKA), or no treatment, using inverse probability of treatment weighted (IPTW) Cox regression. In untreated patients, the rate for ischaemic stroke was 0.70 per 100 person-years and the rate for a bleed was also 0.70 per 100 person-years. Comparing NOAC with no treatment, the stroke rate was lower [hazard ratio (HR) 0.72; 95% confidence interval (CI) 0.56-0.94], and the rate for intracranial haemorrhage (ICH) was not increased (HR 0.84; 95% CI 0.54-1.30). Comparing VKA with no treatment, the rate for stroke tended to be lower (HR 0.81; 95% CI 0.59-1.09), and the rate for ICH tended to be higher during VKA treatment (HR 1.37; 95% CI 0.88-2.14). Comparing NOAC with VKA treatment, the rate for stroke was similar (HR 0.92; 95% CI 0.70-1.22), but the rate for ICH was lower during NOAC treatment (HR 0.63; 95% CI 0.42-0.94). Conclusion: These observational data suggest that NOAC treatment may be associated with a positive net clinical benefit compared with no treatment or VKA treatment in patients at low stroke risk, a question that can be tested through a randomized controlled trial.", keywords = "atrial fibrillation, non-vitamin K antagonist oral anticoagulants, stroke risk, vitamin K antagonists", author = "Komen, {Joris J.} and Anton Potteg{\aa}rd and Mantel-Teeuwisse, {Aukje K.} and Tomas Forslund and Paul Hjemdahl and Bj{\"o}rn Wettermark and Jesper Hallas and Morten Olesen and Marion Bennie and Tanja Mueller and Raymond Carragher and {\O}ystein Karlstad and Kjerpeseth, {Lars J.} and Klungel, {Olaf H.}", year = "2022", month = oct, day = "1", doi = "10.1093/eurheartj/ehac111", language = "English", volume = "43", pages = "3528--3538", journal = "European Heart Journal", issn = "0195-668X", publisher = "Oxford University Press", number = "37", } . European Heart Journal.

Pomalidomide for refractory and relapsed multiple myeloma: A retrospective cohort study of West of Scotland experience following Healthcare Technology Assessment (HTA) @article{2022, doi = {10.1177/10781552221078082}, url = {https://doi.org/10.1177%2F10781552221078082}, year = 2022, month = {mar}, publisher = {{SAGE} Publications}, volume = {28}, number = {2{\_}suppl}, pages = {1--60}, title = {Abstracts}, journal = {Journal of Oncology Pharmacy Practice}} . Journal of Oncology Pharmacy Practice.

Oral anticoagulants in patients with atrial fibrillation at low stroke risk: a multicentre observational study @article{dad6627398814400a4f7539344db2bfa, title = "Oral anticoagulants in patients with atrial fibrillation at low stroke risk: a multicentre observational study", abstract = "Background: There is currently no consensus on whether atrial fibrillation (AF) patients at low risk for stroke (1 non-sex-related CHA2DS2-VASc point) should be treated with an oral anticoagulant.Methods and results: We conducted a multi-country cohort study in Sweden, Denmark, Norway, and Scotland. In total, 59 076 patients diagnosed with AF at low stroke risk were included. We assessed the rates of stroke or major bleeding during treatment with a non-vitamin K antagonist oral anticoagulant (NOAC), a vitamin K antagonist (VKA), or no treatment, using inverse probability of treatment weighted (IPTW) Cox regression. In untreated patients, the rate for ischemic stroke was 0.70 per 100 person-years and the rate for a bleed also 0.70 per 100 person-years. Comparing NOAC to no treatment, the stroke rate was lower (hazard ratio [HR] 0.72; 95% confidence interval [CI] 0.56- 0.94), and the rate for intracranial haemorrhage (ICH) was not increased (HR 0.84; 95% CI 0.54-1.30). Comparing VKA to no treatment, the rate for stroke tended to be lower (HR 0.81; 95% CI 0.59-1.09), and the rate for ICH tended to be higher during VKA treatment (HR 1.37; 95% CI 0.88-2.14). Comparing NOAC to VKA treatment, the rate for stroke was similar (HR 0.92; 95% CI 0.70-1.22), but the rate for ICH was lower during NOAC treatment (HR 0.63; 5% CI 0.42-0.94). Conclusion: These observational data suggest that NOAC treatment may be associated with a positive net clinical benefit compared to no treatment or VKA treatment in patients at low stroke risk, a question that can be tested through a randomised controlled trial.", keywords = "Atrial fibrillation, , Non vitamin K antagonist, Oral anticoagulants, Vitamin K antagonists, Stroke risk, Observational study", author = "Komen, {Joris J} and Anton Potteg{\aa}rd and Aukje Mantel–Teeuwisse and Tomas Forslund and Paul Hjemdahl and Bjorn Wettermark and Jesper Hallas and Morten Olesen and Marion Bennie and Tanja Mueller and Raymond Carragher and {\O}ystein Karlstad and Kjerpeseth, {Lars J{\o}ran} and Klungel, {Olaf H}", year = "2022", month = mar, day = "10", doi = "10.1093/eurheartj/ehac111", language = "English", journal = "European Heart Journal", issn = "0195-668X", publisher = "Oxford University Press", } . European Heart Journal.

Joris J. Komen and Anton Potteg{\aa}rd and Aukje K. Mantel-Teeuwisse and Tomas Forslund and Paul Hjemdahl and Björn Wettermark and Jesper Hallas and Morten Olesen and Marion Bennie and Tanja Mueller and Raymond Carragher and {\O}ystein Karlstad and Lars J. Kjerpeseth and Olaf H. Klungel(2022). Oral anticoagulants in patients with atrial fibrillation at low stroke risk: a multicentre observational study . European Heart Journal. Oxford University Press ({OUP})

Assessing safety at the end of clinical trials using system organ classes @article{ccd10e0b0c7a4314a952269ce08c8d39, title = "Assessing safety at the end of clinical trials using system organ classes: a case and comparative study", abstract = "Recent approaches to the statistical analysis of adverse event (AE) data in clinical trials have proposed the use of groupings of related AEs, such as by system organ class (SOC). These methods have opened up the possibility of scanning large numbers of AEs while controlling for multiple comparisons, making the comparative performance of the different methods in terms of AE detection and error rates of interest to investigators. We apply two Bayesian models and two procedures for controlling the false discovery rate (FDR), which use groupings of AEs, to real clinical trial safety data. We find that while the Bayesian models are appropriate for the full data set, the error controlling methods only give similar results to the Bayesian methods when low incidence AEs are removed. A simulation study is used to compare the relative performances of the methods. We investigate the differences between the methods over full trial data sets, and over data sets with low incidence AEs and SOCs removed. We find that while the removal of low incidence AEs increases the power of the error controlling procedures, the estimated power of the Bayesian methods remains relatively constant over all data sizes. Automatic removal of low-incidence AEs however does have an effect on the error rates of all the methods, and a clinically guided approach to their removal is needed. Overall we found that the Bayesian approaches are particularly useful for scanning the large amounts of AE data gathered.", keywords = "adverse events, Bayesian hierarchy, false discovery rate, safety, system organ class", author = "Raymond Carragher and Chris Robertson", year = "2021", month = nov, day = "18", doi = "10.1002/pst.2148", language = "English", volume = "20", pages = "1278--1287", journal = "Pharmaceutical statistics", issn = "1539-1604", publisher = "John Wiley and Sons Ltd", number = "6", } . Pharmaceutical statistics.

Assessing safety at the end of clinical trials using system organ classes @article{6e6d3e8eb87c4f528238e3d8862672d7, title = "Assessing safety at the end of clinical trials using system organ classes: a case and comparative study", abstract = "Recent approaches to the statistical analysis of adverse event (AE) data in clinical trials have proposed the use of groupings of related AEs, such as by system organ class (SOC). These methods have opened up the possibility of scanning large numbers of AEs while controlling for multiple comparisons, making the comparative performance of the different methods in terms of AE detection and error rates of interest to investigators. We apply two Bayesian models and two procedures for controlling the false discovery rate (FDR), which use groupings of AEs, to real clinical trial safety data. We find that while the Bayesian models are appropriate for the full data set, the error controlling methods only give similar results to the Bayesian methods when low incidence AEs are removed. A simulation study is used to compare the relative performances of the methods. We investigate the differences between the methods over full trial data sets, and over data sets with low incidence AEs and SOCs removed. We find that while the removal of low incidence AEs increases the power of the error controlling procedures, the estimated power of the Bayesian methods remains relatively constant over all data sizes. Automatic removal of low-incidence AEs however does have an effect on the error rates of all the methods, and a clinically guided approach to their removal is needed. Overall we found that the Bayesian approaches are particularly useful for scanning the large amounts of AE data gathered.", keywords = "adverse events, safety, system organ class, Bayesian hierarchy, false discovery rate, pharmacovigilance", author = "Raymond Carragher and Chris Robertson", year = "2021", month = nov, day = "1", doi = "10.1002/pst.2148", language = "English", volume = "20", pages = "1278--1287", journal = "Pharmaceutical Statistics", issn = "1539-1612", publisher = "Wiley", number = "6", } . Pharmaceutical Statistics.

Raymond Carragher, Chris Robertson (2021). Assessing safety at the end of clinical trials using system organ classes: A case and comparative study . Pharmaceutical Statistics.

Raymond Carragher, Chris Robertson (2020). c212: An R Package for the Detection of Safety Signals in Clinical Trials Using Body-Systems (System Organ Classes) . Journal of Open Source Software.

c212 : An R package for the detection of safety signals in clinical trials using body-systems (System Organ Classes) @article{7764f566a4d148c991623453d2c29471, title = "c212 : An R package for the detection of safety signals in clinical trials using body-systems (System Organ Classes)", abstract = "Safety in clinical trials may be characterised by the incidence or occurrence of adverse events. The statistical analysis of this data is complicated by the large number of adverse events recorded, with low event rates, small effect sizes and low power all contributing to the difficulty in determining a robust safety profile for a treatment during the trial process. In addition to end of trial analyses, a number of interim analyses may take place at different time points during the trial lifecycle. These offer the additional statistical challenge of testing accumulating data, with possibly differing recruitment rates on trial arms contributing to a lack of balance in the data. Adverse events are typically defined by medical dictionaries, which provide a common reference terminology for use in and between clinical trials. There are a number of medical dictionaries in current use, all of which provide similar services. One such dictionary is MedDRA (Medical Dictionary for Regulatory Activities), which was developed by the ICH (International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use) and is widely used by regulatory bodies, clinical research organisations (CROs), and pharmaceutical companies. WHO-ART (World Health Organisation Adverse Reaction Terminology) is a similar dictionary maintained by the Uppsala Monitoring Centre for the World Health Organisation Collaborating Centre for International Drug Monitoring. MedDRA and WHO-ART have a similar hierarchical structure consisting of System Organ Classes (SOC) and various grouping and descriptor terms. The MedDRA hierarchical structure consists of five levels: System Organ Class (SOC), High Level Group Terms (HLGT), High Level Terms (HLT), Preferred Terms (PT), and Lower Level Terms (LLT). The PT is a single medical description of a symptom or observation while the LLT is how a patient or data recorder would describe a symptom or observation. Each LLT belongs to one PT and, in general, data will be recorded at the LLT level but reported at the PT level (the adverse event). As of 2020 there are 27 SOCs and over 80,000 LLTs. The grouping of adverse events by SOC (or body-system) provides for possible relationships between the adverse events within a SOC. One consequence of this is the possibility that, for treatments which may affect a particular SOC, there may be raised rates for a number of adverse events within that SOC. A number of methods have recently been proposed to address the statistical issues in adverse event analysis by using these groupings of adverse events by body-system or SOC, taking into account the additional information provided by these relationships to increase the power of detecting real adverse event effects. These methods, Hochberg, 1995; Hu et al., 2010; Matthews, 2006; Mehrotra & Adewale, 2012; Yekutieli, 2008), and Bayesian modelling approaches (Amy Xia et al., 2011; Berry & Berry, 2004; Carragher, 2017b), are implemented in the R package c212.", keywords = "Safety, Clinical Trials, Adverse Events, Body System, System Organ Class, Bayesian Hierarchy, False Discovery Rate, Interim Analysis, R", author = "Raymond Carragher and Chris Robertson", year = "2020", month = dec, day = "4", doi = "10.21105/joss.02706", language = "English", volume = "5", journal = "Journal of Open Source Software", issn = "2475-9066", publisher = "Open Journals", number = "56", } . Journal of Open Source Software.

c212 @article{9900ee3cee8147b3a41d25a42a40c37f, title = "c212: an R package for the detection of safety signals in clinical trials using body-systems (system organ classes)", abstract = " Safety in clinical trials may be characterised by the incidence or occurrence of adverse events. The statistical analysis of this data is complicated by the large number of adverse events recorded, with low event rates, small effect sizes and low power all contributing to the difficulty in determining a robust safety profile for a treatment during the trial process. In addition to end of trial analyses, a number of interim analyses may take place at different time points during the trial lifecycle. These offer the additional statistical challenge of testing accumulating data, with possibly differing recruitment rates on trial arms contributing to a lack of balance in the data. Adverse events are typically defined by medical dictionaries, which provide a common reference terminology for use in and between clinical trials. There are a number of medical dictionaries in current use, all of which provide similar services. One such dictionary is MedDRA (Medical Dictionary for Regulatory Activities), which was developed by the ICH (International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use) and is widely used by regulatory bodies, clinical research organisations (CROs), and pharmaceutical companies. WHO-ART (World Health Organisation Adverse Reaction Terminology) is a similar dictionary maintained by the Uppsala Monitoring Centre for the World Health Organisation Collaborating Centre for International Drug Monitoring. MedDRA and WHO-ART have a similar hierarchical structure consisting of System Organ Classes (SOC) and various grouping and descriptor terms. The MedDRA hierarchical structure consists of five levels: System Organ Class (SOC), High Level Group Terms (HLGT), High Level Terms (HLT), Preferred Terms (PT), and Lower Level Terms (LLT). The PT is a single medical description of a symptom or observation while the LLT is how a patient or data recorder would describe a symptom or observation. Each LLT belongs to one PT and, in general, data will be recorded at the LLT level but reported at the PT level (the adverse event). As of 2020 there are 27 SOCs and over 80,000 LLTs. The grouping of adverse events by SOC (or body-system) provides for possible relationships between the adverse events within a SOC. One consequence of this is the possibility that, for treatments which may affect a particular SOC, there may be raised rates for a number of adverse events within that SOC. A number of methods have recently been proposed to address the statistical issues in adverse event analysis by using these groupings of adverse events by body-system or SOC, taking into account the additional information provided by these relationships to increase the power of detecting real adverse event effects. These methods which include both error controlling procedures for multiple hypothesis testing (Benjamini & Hochberg, 1995; Hu et al., 2010; Matthews, 2006; Mehrotra & Adewale, 2012; Yekutieli, 2008), and Bayesian modelling approaches (Amy Xia et al., 2011; Berry & Berry, 2004; Carragher, 2017b), are implemented in the R package c212 (Table 1).", author = "Raymond Carragher and Chris Robertson", year = "2020", month = dec, day = "4", doi = "10.21105/joss.02706", language = "English", volume = "5", journal = "Journal of Open Source Software", issn = "2475-9066", number = "56", } . Journal of Open Source Software.

A Bayesian hierarchical approach for multiple outcomes in routinely collected healthcare data @article{0fdb1846efa34e29a8bd66d6f253e6bc, title = "A Bayesian hierarchical approach for multiple outcomes in routinely collected healthcare data", abstract = "Clinical trials are the standard approach for evaluating new treatments, but may lack the power to assess rare outcomes. Trial results are also necessarily restricted to the population considered in the study. The availability of routinely collected healthcare data provides a source of information on the performance of treatments beyond that offered by clinical trials, but the analysis of this type of data presents a number of challenges. Hierarchical methods, which take advantage of known relationships between clinical outcomes, while accounting for bias, may be a suitable statistical approach for the analysis of this data. A study of direct oral anticoagulants in Scotland is discussed and used to motivate a modeling approach. A Bayesian hierarchical model, which allows a stratification of the population into clusters with similar characteristics, is proposed and applied to the direct oral anticoagulant study data. A simulation study is used to assess its performance in terms of outcome detection and error rates.", keywords = "Bayesian hierarchy, multiple outcomes, safety outcomes, observational study, direct oral anticoagulants", author = "Raymond Carragher and Tanja Mueller and Marion Bennie and Chris Robertson", year = "2020", month = sep, day = "10", doi = "10.1002/sim.8563", language = "English", volume = "39", pages = "2639--2654", journal = "Statistics in Medicine", issn = "0277-6715", publisher = "Wiley", number = "20", } . Statistics in Medicine.

Raymond Carragher, Tanja Mueller, Marion Bennie, Chris Robertson(2020). A Bayesian hierarchical approach for multiple outcomes in routinely collected healthcare data . Statistics in Medicine. 39. (20). p. 2639--2654. Wiley

CONFERENCE ABSTRACT

Raymond Carragher, Dorothy B. Johnston, Christine McKee, Grace Ings, Helen G. Coleman, Maurice B. Loughrey(2023). Sa1012 VOLUME OF CASE REPORTING IS AN IMPORTANT DETERMINANT OF SERRATED POLYP SUBTYPE DIAGNOSES BY PATHOLOGISTS IN A NATIONAL BOWEL CANCER SCREENING PROGRAMME . Digestive Disease Week 2023. 164. (6). p. S--273--S--274. Elsevier {BV}

Effectiveness of the 23-valent pneumococcal polysaccharide vaccine against invasive pneumococcal disease in European older adults by high risk conditions type @conference{0fd182617d054bb88099ec3a35fbe361, title = "Effectiveness of the 23-valent pneumococcal polysaccharide vaccine against invasive pneumococcal disease in European older adults by high risk conditions type: results of SpIDnet/I-MOVE+ multicentre study", abstract = "Background: Twenty-three-valent polysaccharide (PPV23) and 13-valent pneumococcal conjugate (PCV13) vaccines are licensed for the prevention of invasive pneumococcal disease (IPD) in the elderly. We measured the PPV23 effectiveness against IPD in adults 65+ year-olds by type of high-risk conditions, pooling surveillance data from seven European sites. PPV23 vaccination is recommended in all sites (8-69% uptake) and PCV13 in those with high-risk conditions in two sites (<5% uptake). Methods: Using IPD cases notified between 2012 and 2016, we compared the vaccination status of IPD cases caused by PPV23 serotypes to that of nonPPV23 IPD (controls) stratified by high-risk condition type: none, immunocompetent and immunocompromising high-risk conditions. We defined PPV23 vaccination as having received at least one dose. We computed PPV23 pooled effectiveness as (1 –odds ratio of vaccination)*100 and confidence intervals (95%CI), adjusted for site, age group, sex, and notification year.Results: We included 1955 cases and 856 controls. In the analyses restricted to IPD with no high-risk conditions (n=849) and immunocompetent high-risk conditions (n=1349), cases were younger than controls (p=0.002, p=0.016, respectively), and less likely to present with meningitis (p=0.037, p=0.001, respectively). There was no difference between cases and controls for the IPD with immunocompromising conditions. PPV23 effectiveness was 55% (95%CI: 29-71), 37% (95%CI: 18-52), 7% (95%CI: -33; 34) for IPD with none, immunocompetent and immunocompromising conditions, respectively (p Mantel-Haenzsel test of homogeneity=0.018). Conclusion: Our findings suggest that the type of high-risk condition modifies the PPV23 effectiveness against PPV23 serotypes IPD. The PPV23 effectiveness was higher among healthy older adults and lower among immunocompromised elderly. These results suggest that vaccine effectiveness by type of high-risk conditions should be taken into account when defining pneumococcal vaccination strategies for older adults. ", keywords = "streptococcus pneumoniae, pneumococcal infections, pneumococcal vaccine, vaccine effectiveness, population surveillance", author = "Camelia Savulescu and R. Carragher and {A. SpIDnet/I-MOVE+ group}", year = "2018", month = nov, day = "22", language = "English", note = "European Scientific Conference on Applied Infectious Disease Epidemiology 2018, ESCAIDE 2018 ; Conference date: 21-11-2018 Through 23-11-2018", url = "https://www.escaide.eu/en", } . European Scientific Conference on Applied Infectious Disease Epidemiology 2018, Saint Julian's, Malta, 21/11/18.

CONFERENCE POSTER

Pomalidomide for refractory and relapsed multiple myeloma @conference{6ad8e48a6d3346f0a8c667d29f68812a, title = "Pomalidomide for refractory and relapsed multiple myeloma: a retrospective cohort study of West of Scotland experience following Health Technology Assessment (HTA)", abstract = "BackgroundMyeloma is predominantly a disease of the elderly, many of whom are excluded from clinical trials. In 2014, pomalidomide was accepted for use in combination with dexamethasone by the Scottish Medicines Consortium (SMC) for the treatment of relapsed and refractory multiple myeloma patients with at least two prior therapies. The trial reported a median progression free survival (PFS) and overall survival (OS) of 4 months and 12.7 months respectively. However, within their assessment SMC noted uncertainties relating to younger age and fitness of patients within the trial relative to expected eligible population in Scotland. It was also noted that the trial population may have been more heavily pre-treated (median 5 treatments).Aims & objectivesThe aim of this study was to use electronic record linkage (ERL) of healthcare data from patients treated across the four West of Scotland (WoS) Health Boards to describe characteristics and outcomes of pomalidomide patients relative to the trial population used to inform the SMC assessment. Objectives were: to describe OS and identify if PFS could be derived. Methods Patients treated with pomalidomide, between 2015 and 2017 within the WoS were identified using the Chemotherapy Electronic Prescribing and Administration System (CEPAS). This information was linked to data from the Prescribing Information System (PIS; community prescribing); the Scottish Cancer Registry (SMR06); Scottish Morbidity Records, inpatient episodes and outpatient appointments (SMR01 & SMR00); National Register of Scotland, death records (NRS) and the Scottish Care Information (SCI) store (laboratory test results) within the NHS GGC Safe Haven. Statistical analysis was performed using R{\textregistered}. OS and PFS was estimated using Kaplan-Meier method, and Cox{\textquoteright}s proportional-hazards model was used to estimate unadjusted hazard ratios (HR) for the clinical variables.Results78 patients were identified; 65% were male and median age was 69 years (range 43-87). Performance status at baseline was 60% 0-1, 14% 2 and not available for 26%. Laboratory data was only readily available for patients treated in one health board (44%). Median number of prior treatments was 3 (Interquartile range 2-3). Data were censored on 30th November 2018 at which time; 76 patients had stopped and 20 remained alive (median follow up 12 months). The median duration of pomalidomide treatment was 3.9 months and median OS was 12.9 months. Poorer performance status and ≥3 prior treatments increased the death hazard (Unadjusted HR 4.15 (95% CI 1.74-9.93) and HR 1.72 (95% CI 1.01-2.92) respectively). Discussion/ConclusionWoS patients were older and had received fewer prior treatments, in line with the uncertainties highlighted within the SMC assessment. However, median OS was similar to that reported in the pivotal study. Description of PFS was hampered by inability to access all laboratory data for patients as SCI store is not a nationally held data set. Duration of therapy, often considered as a surrogate for PFS was nonetheless, similar to PFS reported in the trial.ERL is a feasible method to assess local outcomes when there are potential generalisability issues highlighted within the HTA assessment and may provide useful local context for patients, clinicians and funders. ", keywords = "oncology, myeloma, pomalidomide, survival, electronic record usage, data linkage", author = "Kelly Baillie and Carragher, {Raymond Bernard} and Christine Crearie and Jennifer Laskey and Marion Bennie and Grant McQuaker and Richard Soutar", year = "2021", month = oct, day = "8", language = "English", note = "British Oncology Pharmacy Association (BOPA) 24th Annual Symposium ; Conference date: 08-10-2021 Through 10-10-2021", } . British Oncology Pharmacy Association (BOPA) 24th Annual Symposium, 8/10/21.

Mueller T, Carragher R, Robertson C, Bennie M. Temporal and spatial variation in the prescribing of oral anticoagulants in Scotland - a nationwide record linkage study. EuroDURG 2020, 4-7 March 2020, Szeged, Hungary.

Bayesian hierarchical approaches for multiple outcomes in routinely collected healthcare data @conference{f37aff5fb79a4d1bb1a550a6745a9fad, title = "Bayesian hierarchical approaches for multiple outcomes in routinely collected healthcare data", abstract = "Background: Routinely collected healthcare data provides a rich environment for the investigation of drug performance in the general population, while also offering the possibility of assessing rare outcomes. The statistical analysis of this data poses a number of challenges. The data may be biased and lack the structure and balance provided by the drugs{\textquoteright} clinical trials. Outcomes are often modelled individually with an associated lack of control for multiple comparisons, as well as a difficulty in assessing multiple risks. Methods: Bayesian models provide methods for analysing multiple clinical outcomes, using relationships between outcomes and handling the types of multiple comparison issues which may occur when using multiple single-variate approaches. Lack of balance within the data may be catered for by dividing the population into clusters with similar characteristics, allowing within cluster inferences to be made. A Bayesian hierarchical model for multiple outcomes is proposed and applied to data from a safety and effectiveness study of direct oral anticoagulants (DOACs) in Scotland 2009 – 2015.Results: The Bayesian modelling results were comparable to the results from the original safety and effectiveness study, with the additional benefit of balancing patient clusters and controlling for relationships in the data.Conclusion: Bayesian hierarchical models are a suitable approach for modelling routinely collected healthcare data. There is the possibility of moving to an integrated Bayesian approach, with the inclusion of treatment relationships; uncertainty regarding cluster membership; and treatment allocation in the model, eventually leading to more reliable treatment decisions.", keywords = "Bayesian hierarchy, safety, direct oral anticoagulants (DOACs), stratification, clusters", author = "Carragher, {Raymond Bernard} and Tanja Mueller and Marion Bennie and Chris Robertson", year = "2020", month = mar, day = "6", language = "English", note = "EuroDURG 2020 ; Conference date: 03-03-2020 Through 07-03-2020", } . EuroDURG 2020, Szeged, Hungary, 3/03/20.

Effectiveness of the 23-valent pneumococcal polysaccharide vaccine against Invasive Pneumococcal Disease incidence in European adults aged 65 years and above @conference{9ed3564e550f4698ad9ba4ed6eb4f4ae, title = "Effectiveness of the 23-valent pneumococcal polysaccharide vaccine against Invasive Pneumococcal Disease incidence in European adults aged 65 years and above: results of SpIDnet/I-MOVE+ multicentre study (2012-2016)", abstract = "Background and Aims: We measured the effectiveness of 23-valent pneumococcal polysaccharidic vaccine(PPV23) against invasive pneumococcal disease (IPD) in 65+ year-olds, pooling surveillance data from seven European sites. PPV23 vaccination is recommended in all sites (8-69% uptake) and PCV13 in high risk groups in two sites (<5%uptake). Methods: We compared the vaccination status of IPD cases caused byPPV23 serotypes (cases) to that of nonPPV23 IPD (controls) notified between2012 and 2016. We defined PPV23 vaccination as at least one dose. PPV23 pooled effectiveness was calculated as (1 –odds ratio of vaccination)*100, adjusted for site, age, sex, underlying conditions and year. We stratified PPV23effectiveness by time since last dose of vaccine: <2, 2-4, 5-9 and 10+years. Results: We included 2011 cases and 878 controls. Compared to controls,cases were younger (p=0.001), less likely to have an underlying condition(p=0.025), more likely to be admitted for intensive care (p=0.038) and to have pneumonia (p=0.005). PPV23 effectiveness was 24% (95%CI: 4; 41) against PPV23-serotypes.By serotype, PPV23 effectiveness ranged between -2% (95%CI: -48; 30) against serotype 3 (n=687) and 55% (95%CI: 15; 76) against serotype 9N IPD (n=540). By years since vaccination, PPV23 effectiveness was 43% (95%CI: 3-66) and 15%(95%CI: -25; 43) for <2 years and 10+ years, respectively. Conclusion: Our findings suggest a low PPV23 effectiveness against IPD caused by PPV23serotypes in the elderly, varying by serotype, and higher in the first two years after vaccination. Despite low effectiveness, PPV23 in the elderly may prevent at least 25% of cases among vaccinated.", keywords = "pneumococcal, pneumoniae, IPD, Vaccine, Effectiveness, PPV23, Elderly", author = "Camelia Savulescu and P. Valentiner-Branth and J. Mereckiene and B.A. Winje and P. Ciruela and P. Latasa and M. Guevara and Carragher, {Raymond Bernard} and T. Dalby and M. Corcoran and D.F. Vestrheim and C. Munoz-Almagro and J.C. Sanz and J. Castilla and A. Smith and E. Colzani and L. Pastore-Celentano and G. Hanquet", year = "2018", month = apr, day = "17", language = "English", note = "11th International Symposium on Pneumococci and Pneumococcal Diseases, ISPPD ; Conference date: 15-04-2018 Through 19-04-2018", } . 11th International Symposium on Pneumococci and Pneumococcal Diseases, Melbourne, Australia, 15/04/18.

Detection of safety signals in randomised controlled trials using groupings @conference{fa7e4cff703e4b90beec04a8b15dcbcf, title = "Detection of safety signals in randomised controlled trials using groupings", abstract = "Many different types of adverse event are routinely recorded during clinical trials. The statistical analysis of this data may need to take into account:1.potential multiple comparison issues;2.low power - effect sizes of adverse events in clinical trials are generally small.The use of methods which use possible groupings of adverse events (e.g. by System Organ Class) in their statistical analyses may result in an increase in the power to detect adverse event incidence while maintaining control over the Type-I error rate. ", keywords = "safety, clinical trials, adverse events, body system, system organ class, Bayesian hierarchy, false discovery, rate, interim analysis", author = "Raymond Carragher", year = "2017", month = sep, day = "5", language = "English", note = "Royal Statistical Society Conference 2017, RSS2017 ; Conference date: 04-09-2017 Through 07-09-2017", } . Royal Statistical Society Conference 2017, Glasgow, 4/09/17.

DATA SET

Carragher, Raymond Bernard(2021). Comparative study for: "Assessing safety at the end of clinical trials using system organ classes: a case and comparative study" .

Carragher, Raymond Bernard(2020). Bayesian Hierarchical Possion Models for Mulitple Grouped Outcomes with Clustering - Simulation Study . University of Strathclyde

SOFTWARE

Carragher, Raymond(2019). Bayesian Hierarchical Possion Models for Mulitple Grouped Outcomes with Clustering . Zenodo. Zenodo

(2017). c212: Methods for Detecting Safety Signals in Clinical Trials Using Body-Systems (System Organ Classes) .

ONLINE RESOURCE

Carragher, Raymond(2019). rcarragh/c212: Release 0.95 to CRAN . Zenodo. Zenodo

REPORT

Associations between Ambient Outdoor Temperature and Patterns of Morbidity and Mortality in Scotland @book{462203b15c09454c915f962d8d4e8d55, title = "Associations between Ambient Outdoor Temperature and Patterns of Morbidity and Mortality in Scotland", abstract = "This report investigates the association between ambient air temperature and health impacts, measured as morbidity (hospital admissions) and mortality, in Scotland to determine what evidence there is to reject the (null) hypothesis that there is no relationship. ", keywords = "ambient temperature, mortality, morbidity", author = "Colin Ramsay and C. Robertson and Ray Carragher and Stephen Corson", year = "2018", month = mar, day = "31", language = "English", publisher = "National Centre for Resilience", } .

OTHER

c212: Methods for Detecting Safety Signals in Clinical Trials Using Body-Systems (System Organ Classes) @misc{a45fd9354b4d4050b9b14912bdf94afb, title = "c212: Methods for Detecting Safety Signals in Clinical Trials Using Body-Systems (System Organ Classes)", abstract = "This software package implements a number of methods for the detection of safety signals in Clinical Trials based on groupings of adverse events by body-system or system organ class. The methods include an implementation of the Three-Level Hierarchical model for Clinical Trial Adverse Event Incidence Data of Berry and Berry (2004) , an implementation of the same model without the Point Mass (Model 1a from Xia et al (2011)), and extended Bayesian hierarchical methods based on system organ class or body-system groupings for interim analyses. The package also implements a number of methods for error control when testing multiple hypotheses, specifically control of the False Discovey Rate (FDR). The FDR control methods implemented are the Benjamini-Hochberg procedure, the Double False Discovery Rate, the Group Benjamini-Hochberg and subset Benjamini-Hochberg methods. Also included are the Bonferroni correction and the unadjusted testing procedure.", keywords = "System organ class, clinical trials, safety signals", author = "Raymond Carragher", year = "2017", month = jan, day = "7", language = "English", publisher = "University of Strathclyde", } .