2025-26 Project (Matthewman & Langan)

Long-term safety of glucocorticoids across treatments modalities

SUPERVISORY TEAM

Supervisor

Dr Julian Matthewman at LSHTM
Email: julian.matthewman1@lshtm.ac.uk

Co-Supervisor

Professor Sinéad Langan at LSHTM
Email: sinead.langan@lshtm.ac.uk

PROJECT SUMMARY

Project Summary

This project aims to investigate the long-term safety of glucocorticoids, widely used to treat inflammatory conditions, by examining different forms (oral, inhaled, and topical) and their associated risks. While glucocorticoids have been effective for decades, they are linked to adverse effects across multiple organ systems. It is crucial to assess the safety of continued steroid use, especially inhaled and topical steroids, often prescribed long-term, and combined exposures through different routes. 

The student will be working with longitudinal electronic health records data, studying multiple exposures, outcomes and underlying conditions using high-throughput techniques and efficient and reproducible workflows. Complex exposure definitions will be applied to define time-changing steroid exposure, also aiming to disentangle the effects of steroids form the severity of the underlying disease. A placement in either Canada or Denmark will give the opportunity to work in a different setting, and replicating the study in another country will strengthen results.

Project Key Words

Glucocorticoids, multimodal, high-throughput, inhaled steroids, topical

MRC LID Themes

  1. Health Data Science
  2. Translational and Implementation Research

Skills

MRC Core Skills

  1. Quantitative skills

Skills we expect a student to develop/acquire whilst pursuing this project

• Reproducible and efficient analytical workflows
• Skills in epidemiological study design, statistics and causal inference
• Developing ideas from protocol to publication

Routes

Which route/s are available with this project?

  • 1+4 = Yes
  • +4 = Yes

Possible Master’s programme options identified by supervisory team for 1+4 applicants:

  • LSHTM – MSc Epidemiology
  • LSHTM – MSc Health Data Science
  • LSHTM – MSc Medical Statistics

Full-time/Part-time Study

Is this project available for full-time study? Yes
Is this project available for part-time study? Yes

Location & Travel

Students funded through MRC LID are expected to work on site at their primary institution, meeting – at the minimum – the institutional research degree regulations and expectations. Students may also be required to travel for conferences (up to 3 over the duration of the studentship), and for any required training (for research degree study). Other travel expectations and opportunities highlighted by the supervisory team are noted below.

Primary location for duration of this research degree: LSHTM, London

Travel requirements for this project: A 3-month visit to either the University of Aarhus or the University of Toronto is envisaged.

Eligibility/Requirements

Particular prior educational requirements for a student undertaking this project

  • Minimum LSHTM institutional eligibility criteria for doctoral study.
  • Health and data science related MSc, e.g., Health data science, Epidemiology, Medical statistics

Other useful information

  • Potential Industrial CASE (iCASE) conversion? = No

PROJECT IN MORE DETAIL

Scientific description of this research project

Background 
Glucocorticoids such as prednisolone, also known as steroid tablets, inhalers or creams, have been used in the treatment of several inflammatory conditions for decades. They are known to be associated with adverse effects across multiple organ systems, including bone fractures, diabetes, hypertension and infections. The landscape of therapeutics is changing, with disease modifying “steroid-sparing” therapies offering alternatives to long-term oral or systemic steroids. However, evidence is emerging on risks associated with other modalities. To treat atopic and allergic conditions, such as asthma and eczema that commonly co-occur, inhaled and topical steroids are often used in combination and over many years. Thus studying multimodal long-term safety is essential. Rich data are available from UK primary care, with follow-up time now available for decades; long enough to study adverse effects compounding over many years. However there has been a lack of comprehensive research into long-term steroid safety across modality, outcomes and type of underlying disease.

Objectives
Study the long term safety of glucocorticoids
• by steroid modality (e.g., oral, inhaled, topical)
• by combination of modalities (e.g., inhaled and topical)
• by outcome (e.g., bone fractures, diabetes, hypertension, infections)
• by underlying disease (or combination of diseases)

Techniques
The student will be working with longitudinal Electronic health records data. Studying multiple exposures, outcomes and underlying conditions will require the use of high-throughput techniques to study design and efficient and reproducible workflows. Complex drug exposure definitions will need to be applied, to define steroid exposure, e.g., by cumulative dose and recency and being able to account for time-changing steroid exposure. This will also include assessing multimodal steroid exposure. Suitable methods of confounding adjustment need to be used, in particular to disentangle the effects of steroids from the severity of the underlying disease

Data
CPRD Aurum, which contains UK primary care data that can be linked to several other data sources (e.g., hospital data), captures diagnoses, symptoms, prescriptions, referrals and tests. International comparisons can add considerable value to this work and we have close collaborations with both Danish and Canadian epidemiological researchers. We will therefore explore (partial) replication of the study with either Danish or Canadian national health data; which would involve a 3 month placement at either site.

Risks
The risk of data access issues with CPRD Aurum is low. There are risks concerning slow computation, which may be addressed through the use of LSHTM’s high performance compute cluster.

Further reading

Relevant preprints and/or open access articles:
(DOI = Digital Object Identifier)

Additional information from the supervisory team

The supervisory team has provided a recording for prospective applicants who are interested in their project. This recording should be watched before any discussions begin with the supervisory team.

Matthewman-Langan recording

MRC LID LINKS

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