The safety of glucocorticoids in patients with inflammatory musculoskeletal conditions

Lead Research Organisation: University of Manchester
Department Name: Medical and Human Sciences

Abstract

Glucocorticoids, also known as steroids, are drugs commonly used for the treatment of rheumatoid arthritis and other inflammatory conditions. Steroids are a good treatment because they quickly ease joint pain, swelling and stiffness, thus improving disability. However, as with most medication, there are potential side effects.

When starting medication, most patients want to know their chance of developing side effects. However, we don‘t know accurately how commonly side effects occur, what dose of steroid leads to side effects, or what sort of person is particularly at risk. The chance of side effects probably varies according to many factors, including how old a patient is, their gender, whether they have other diseases, or are taking other medication. This research aims to answer these questions, and to provide a likelihood of side effects tailored to the individual.

Only patients themselves know whether they take their medicines, at what dose, or whether they develop side effects. In order to improve risk measurement, we need to collect such information directly from patients. Then, having measured risk, we need to improve the way we communicate this information to patients. This project aims to develop electronic systems to advance this two-way communication.

Technical Summary

Aim
To quantify the risk of single and multiple adverse events in patients with inflammatory musculoskeletal conditions treated with glucocorticoid (GC) therapy.
Objectives
To explore the association between time-varying GC dosage and route of administration of GC and outcome.
To develop and validate a predictive tool to estimate likelihood of GC-associated adverse events.
To address the influence of adherence upon risk estimates.
To better understand the benefit/ harm balance of GC use.
To improve risk communication through development of an electronic visual tool
Design and Methodology
The planned analyses will use databases that are established or in development. First, nested case-control and cohort studies, with modelling of time-varying GC exposure including dose, will be undertaken using respected UK primary care databases: the General Practice Research Database and The Health Improvement Network. Prediction modelling will be used to identify patients at risk of GC-associated adverse events (including infection, cardiovascular disease, diabetes, fractures), in one dataset with validation in the second dataset. In order to address the influence of factors captured only in secondary care, such as parenteral GC therapy and disease severity measures, further analysis will be undertaken in two additional databases under development, the arc Early Inflammatory Arthritis Information System and the NorthWest e-Health e-Labs project. Additional funding will be sought to develop and implement novel technology to capture patient reported outcome measures and adherence data, and to develop an electronic visual tool for risk communication.
Scientific and medical opportunities
It is not clear which GC treatment regimes place patients at risk of adverse events, what degree of risk is conferred, or what predisposes patients to such events. This makes accurate communication of risk difficult. The work described above will unpick some of the complexities of GC-associated adverse events. It will also move risk estimation towards personalised risk assessment, whereby patients can be informed of their individual risk of side effects given their profile, including demographics, disease characteristics and co-morbidity.
Pharmacoepidemiology is currently limited by the scope of available datasets. These projects will improve capture of clinical data, both from clinicians and directly from patients. Although focussed on GC safety, the skills, techniques and visual tools developed in these projects will have wider application for investigating the safety of other medications.

Publications

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Dixon WG (2014) A dynamic model of patient consent to sharing of medical record data. in BMJ (Clinical research ed.)

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Dixon WG (2011) Bisphosphonates and esophageal cancer--a pathway through the confusion. in Nature reviews. Rheumatology

 
Title Bedrock: Exhibition of Nicola Dale's artist-in-residence time in the Centre for Epidemiology 
Description This innovative arts-science collaboration allowed visual artist Nicola Dale to undertake a residency in the Arthritis Research UK Centre for Epidemiology (CfE) that was founded in 1954. The initial aim was to research, develop and create artworks inspired by the CfE's archive, and to reflect the relevance of the archive in today's medical and epidemiological practice. Nicola focussed on an x-ray archive collected by the first Director, Dr John Lawrence, in a 1950's study of rheumatism in local miners. Further supported by a Wellcome Trust ISSF Public Engagement Award, the work extended to include interviews and workshops with patients and local miners in collaboration with the Centre for History of Science, Technology & Medicine. Local miners were invited through a live discussion on BBC Radio Manchester. These interviews significantly influenced several art pieces. A further collaboration with the Granada Centre for Visual Anthropology allowed students to document the project through short films, shown in the final exhibition. The project was conceived to make epidemiology accessible through a creative collaboration interweaving art, history, science and medicine. 
Type Of Art Artwork 
Year Produced 2016 
Impact The work culminated with a public exhibition "Bedrock" in Salford from 28-31st January that featured sculptures and 2-D artwork, an artist's talk as well as films of the creative process and an uncovered 1952 film of Dr Lawrence at the Walkden Miners Clinic from the BFI archive. The exhibition had significant press interest including the BBC and Manchester Evening News. There were 188 visitors over three days including members of the public, arthritis patients, miners, artists, MA students from the Granada Centre, clinicians and UoM researchers. During the show there were 1052 visitors to www.nicoladale.com. Visitor book comments included: "Such a well researched project and so painstakingly, imaginatively and beautifully executed" "An epic subject well deserving the epic exposition." "Moving, insightful, reflective, poetic. Wonderful collaboration between Nicola, Manchester University and a range of audiences." Nicola has maintained a project blog and is producing a commemorative publication. In addition to the exhibition, further engagement and impact included visits to the artist's studio for the research group, encouraging their own involvement in traditional and creative public engagement. The project has an important legacy in the artwork to be mounted in the CfE and within outpatients at Salford Royal Hospital. The work will also be showcased during the European City of Science Festival (July 2016) and will be included in the Manchester Histories Festival (June 2016). 
URL http://www.nicoladale.com/bedrock---work-in-progress.html
 
Description CHM Working Group on the safety and efficacy of insulins
Geographic Reach National 
Policy Influence Type Participation in advisory committee
 
Description EULAR recommendations for core dataset in RA
Geographic Reach Multiple continents/international 
Policy Influence Type Membership of a guideline committee
 
Description EULAR taskforce on steroid safety
Geographic Reach Europe 
Policy Influence Type Membership of a guideline committee
Impact Guidelines on the safe prescribing of glucocorticoid therapy will improve outcomes for patients treated with such therapies, avoiding unnecessary doses through guiding clinical practice
 
Description Glucocorticoid infection risk included in UpToDate
Geographic Reach Multiple continents/international 
Policy Influence Type Influenced training of practitioners or researchers
 
Description Guidelines for giant cell arteritis
Geographic Reach Multiple continents/international 
Policy Influence Type Membership of a guideline committee
 
Description MHRA Ad Hoc Committee for the review of over the counter analgesics
Geographic Reach National 
Policy Influence Type Implementation circular/rapid advice/letter to e.g. Ministry of Health
Impact Improved balance of benefits and harms of prescribed over the counter medication
 
Description Arthritis Research UK Centre for Epidemiology
Amount £2,500,000 (GBP)
Organisation Versus Arthritis 
Start 08/2012 
End 07/2017
 
Description Centres of Excellence
Amount £1,999,419 (GBP)
Funding ID 21755 
Organisation Versus Arthritis 
Start 08/2018 
End 07/2023
 
Description Cross-Farr small awards
Amount £15,000 (GBP)
Organisation Farr Institute of Health Informatics Research 
Sector Academic/University
Country United Kingdom
Start 07/2016 
End 07/2017
 
Description E-Health Centres of Excellence
Amount £4,500,000 (GBP)
Organisation Medical Research Council (MRC) 
Sector Academic/University
Country United Kingdom
Start 03/2013 
End 03/2018
 
Description Evaluating the Accuracy of New Methods of Pharmacosurveillance: Computerized Administrative Data and Electronic Prescribing and Drug Management Systems
Amount £747,000 (GBP)
Funding ID 99305 
Organisation Canadian Institutes of Health Research 
Sector Public
Country Canada
Start 04/2011 
End 04/2015
 
Description Generic roll-out of the Arthritis Research UK Catalogue of Studies
Amount £15,000 (GBP)
Funding ID 20878 
Organisation Versus Arthritis 
Start 07/2014 
End 01/2016
 
Description Granulomatosis with Polyangiitis: Defining the risk of infection associated with the disease and treatment, Arthritis Research UK
Amount £30,182 (GBP)
Funding ID 20613 
Organisation Versus Arthritis 
Start 04/2014 
End 03/2015
 
Description HS&DR
Amount £618,424 (GBP)
Organisation National Institute for Health Research 
Sector Public
Country United Kingdom
Start 09/2015 
End 08/2017
 
Description INBANK Project Manager & Project Support Officer
Amount £269,382 (GBP)
Organisation Versus Arthritis 
Start 10/2011 
End 10/2014
 
Description INBANK Scientific Lead (Research Funding Award)
Amount £53,876 (GBP)
Organisation Versus Arthritis 
Start 04/2012 
End 12/2014
 
Description ISSF
Amount £3,450 (GBP)
Organisation Wellcome Trust 
Sector Charity/Non Profit
Country United Kingdom
Start 07/2015 
End 01/2016
 
Description MRC Confidence in Concept 2
Amount £106,270 (GBP)
Organisation Medical Research Council (MRC) 
Sector Academic/University
Country United Kingdom
Start 10/2014 
End 06/2015
 
Description Project Grant: Psoriasis in UK BIobank
Amount £165,670 (GBP)
Organisation Versus Arthritis 
Start 03/2016 
End 02/2019
 
Description Project Grant: Sleep-RA
Amount £249,990 (GBP)
Funding ID 21188 
Organisation Versus Arthritis 
Start 04/2016 
End 03/2019
 
Description Salford EPR for research
Amount £43,416 (GBP)
Organisation Salford Royal NHS Foundation Trust 
Sector Public
Country United Kingdom
Start 08/2013 
End 08/2014
 
Description Special Strategic Award: Cloudy with a Chance of Pain
Amount £199,212 (GBP)
Funding ID 21225 
Organisation Versus Arthritis 
Start 09/2015 
End 08/2017
 
Description Special Strategic Award: REMORA
Amount £394,000 (GBP)
Organisation Versus Arthritis 
Start 02/2015 
End 02/2017
 
Title Drug preparation algorithm 
Description Algorithm and reporting framework for increasing the efficiency and transparency of drug data preparation methods 
Type Of Material Improvements to research infrastructure 
Year Produced 2017 
Provided To Others? Yes  
Impact Markedly increased the efficiency of data preparation for users 
 
Title DrugPrep 
Description Framework to improve the efficiency and transparency of drug exposure data preparation 
Type Of Material Improvements to research infrastructure 
Year Produced 2018 
Provided To Others? Yes  
Impact Marked reduction in the time spent to prepare drug exposure data, leading to more efficient use of funders' money 
URL https://zenodo.org/record/1313712#.XHZOtFP7Txo
 
Description Anna Cox 
Organisation University College London
Department Department of Computer Science
Country United Kingdom 
Sector Academic/University 
PI Contribution Connection made with research group interested in studying Citizen Science projects
Collaborator Contribution Contribution to design and evaluation of Citizen Science experiment
Impact None to date
Start Year 2015
 
Description Dynamic consent 
Organisation London School of Economics and Political Science (University of London)
Country United Kingdom 
Sector Academic/University 
PI Contribution Provided clinical setting for application of dymanic consent model
Collaborator Contribution Established the model of dynamic consent and its practical application through a RTSB award
Impact Publications
Start Year 2012
 
Description Dynamic consent 
Organisation University of Oxford
Country United Kingdom 
Sector Academic/University 
PI Contribution Provided clinical setting for application of dymanic consent model
Collaborator Contribution Established the model of dynamic consent and its practical application through a RTSB award
Impact Publications
Start Year 2012
 
Description EULAR Registers and Observational Drug Studies (RODS) 
Organisation The European League Against Rheumatism (EULAR)
Country Switzerland 
Sector Charity/Non Profit 
PI Contribution Co-Lead of EULAR RODS Study Group
Collaborator Contribution Community of registers and observational drug studies across European rheumatology. Inaugural meeting (convened by me) in Prague Nov 14/15th 2013
Impact Inaugural meeting of RODS Working Groups in progress
Start Year 2012
 
Description EULAR taskforce on steroid safety 
Organisation The European League Against Rheumatism (EULAR)
Country Switzerland 
Sector Charity/Non Profit 
PI Contribution Contributed to guidelines for the use of steroids in inflammatory musculoskeletal disease
Collaborator Contribution Contributed to guidelines for the use of steroids in inflammatory musculoskeletal disease
Impact Publication in draft
Start Year 2014
 
Description Google Android Wear 
Organisation Google
Country United States 
Sector Private 
PI Contribution Established new collaboration between University of Manchester and Google Android Wear. Co-designed a smartwatch app for self-reported pain and activity alongside passively collected activity data. Will be Google Android Wear's first health study with a view to ongoing collaboration. The study will be nested within Cloudy with a Chance of Pain
Collaborator Contribution Developed partnership through direct contact with lead engineer at Google Android Wear, proposing the research study and partnership
Impact Project is expected to launch in April 2017. Google providing 100 smartwatches and in kind contributions from software and hardware engineering
Start Year 2016
 
Description Goran Nenadic 
Organisation University of Manchester
Country United Kingdom 
Sector Academic/University 
PI Contribution Collaborative working on multiple projects: automated deidentification of EPR letters, extracting dose information from prescriptions, narratives within HealthUnlocked
Collaborator Contribution Computer Science methods to help solve epidemiological challenges
Impact One publication to date
Start Year 2015
 
Description Health Unlocked 
Organisation Health Unlocked
Country United Kingdom 
Sector Private 
PI Contribution Surveys within HU platform. Analysis of narratives within HU communities
Collaborator Contribution Data provision and extension of their HealthGraph
Impact No outputs to date
Start Year 2016
 
Description Michal Abrahamowicz 
Organisation McGill University
Department Department of Epidemiology, Biostatistics and Occupational Health
Country Canada 
Sector Academic/University 
PI Contribution Input of clinical and epidemiological challenges that require biostatistical solutions
Collaborator Contribution Biostatistical solutions to clinical and epidemiological challenges
Impact Publications
Start Year 2010
 
Description Robyn Tamblyn 
Organisation McGill University
Department Department of Epidemiology, Biostatistics and Occupational Health
Country Canada 
Sector Academic/University 
PI Contribution Co-applicant on international pharmacosurveillance project. Run UK arm of three international sites
Collaborator Contribution Co-applicant on international pharmacosurveillance project. Coordinated by Robyn Tamblyn @ McGill
Impact Publications in progress. Abstracts accepted at ISPE meeting
Start Year 2010
 
Description The Office for Creative Research 
Organisation The Office for Creative Research (OCR)
Country United States 
Sector Private 
PI Contribution Established connection with OCR in 2015 to explore opportunities for collaboration around Cloudy with a Chance of Pain and implementation of Dynamic Consent interface
Collaborator Contribution Developing data visualisations and citizen science project
Impact No outputs yet
Start Year 2015
 
Description uMotif 
Organisation uMotif
Country United Kingdom 
Sector Private 
PI Contribution Co-design of smartphone application to collect data on musculoskeletal disease, including use of accelerometer and GPS data
Collaborator Contribution Use of their configurable smartphone application and supporting systems
Impact MRC Confidence in Concept award Funding for Cloudy with a Chance of Pain, extending work to linkage to wearable devices
Start Year 2013
 
Description BBC Breakfast 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Media (as a channel to the public)
Results and Impact Video feature and then interview on the 'BBC Breakfast couch'. Viewing figures of 7M. Significant public response following broadcast with recruitment spike of around 4000 new registrants that day. Recruiting one new user per second following the show
Year(s) Of Engagement Activity 2016
 
Description BBC2's Trust Me I'm a Doctor 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Media (as a channel to the public)
Results and Impact Broadcast planned for January 2016. Should drive recruitment

Due to broadcast Jan 2016
Year(s) Of Engagement Activity 2015
 
Description Bedrock: Public exhibition of artwork from Centre for Epidemiology artist in residence 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact Three-day public exhibition "Bedrock" in Jan 2016, with BBC coverage (funded by the Wellcome Trust)
Legacy artwork to be mounted in Centre for Epidemiology & Salford Royal Hospital
Due to feature in Manchester Histories Festival June 2016 & European City of Science Festival 2016
Year(s) Of Engagement Activity 2016
URL http://www.nicoladale.com/uploads/1/0/3/6/10361696/ndale_uom_residency_info_2015.pdf
 
Description National newspaper coverage 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Media (as a channel to the public)
Results and Impact Articles about Cloudy with a Chance of Pain features in multiple national newspapers, both print and online editions. National papers included the Independent, The Mirror, Daily Express and Daily Mail.
Year(s) Of Engagement Activity 2016
URL http://www.independent.co.uk/life-style/health-and-families/health-news/smartphone-app-could-help-un...