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Moving beyond frequency tables for the analysis and presentation of harm outcomes in randomised controlled trials


   Wolfson Institute of Population Health

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  Dr Rachel Phillips, Dr Victoria Cornelius, Dr Odile Sauzet  No more applications being accepted  Competition Funded PhD Project (Students Worldwide)

About the Project

Background: Good practice statistical analysis methods for assessing potential benefits (often described as “efficacy” or primary and secondary outcomes) are well established. Despite guidelines and recommendations promoting good practice, there is considerable research demonstrating that potential harms are assessed and analysed inconsistently and inadequately, and poor quality reporting of adverse events (means by which we capture harms) observed in RCTs limits the use of RCT evidence for purposes including systematic reviews and clinical practice guidelines. Better adoption of existing guidelines and recommendations would improve the utility of RCTs but additional research and recommendations are needed to improve the methods used to assess, analyse, report, and synthesize evidence about harms.

A much-neglected area of discussion is that for the analysis of adverse events where accepted good analysis practice is sometimes unknown to trialists. Dominant current practice relies on the use of unadjusted hypothesis testing to detect between-arm imbalance. Aspects such as discounting participants’ multiple episodes and competing events, dichotomising continuous measures, use of inappropriate analysis populations and ignoring exposure-time are common. 

A 2019 review provides a comprehensive picture of statistical methods that have been specifically developed or adapted for the analysis of adverse events in RCTs, revealing a broad range of published statistical methods that account for the complexities of harm outcomes. Many of which could be adopted into current practice with relative ease and could potentially lead to improved analysis of harms. There is an opportunity for researchers to move away from the prevalent simplistic approaches currently used but an evaluation and comparison of existing methods is required to identify optimal methods, which would underpin development of best practice guidelines for analysis and identify gaps for future research.

Aim: Identify optimal statistical analysis methods for the analysis of harm outcomes in RCTs.

Objectives: (1) Of the available methods proposed for the analysis of harm outcomes identify the optimal analysis approach(es) specifically for non-prespecified emerging harms utilising all available information (e.g. recurrent events, exposure time etc.) using simulation and case-study examples.

(2) Develop recommendations for best practice approaches for the analysis of harm outcomes in conjunction with the clinical trial community (e.g. CTU and industry statisticians, regulators and journal editors)

(3) Develop tools (such as software) for implementation of the optimal approaches and case studies/tutorials to demonstrate use, ensuring ease of adoption by the clinical trial community.

Supervision: Primary: Rachel Phillips (Pragmatic Clinical Trials Unit, QMUL)

Secondary: Victoria Cornelius (Imperial Clinical Trials Unit, Imperial College London) and Odile Sauzet (Bielefeld School of Public Health, Bielefeld University)

Students will be encouraged to explore collaborations with TMRP Outcomes working group members and other relevant TMRP working groups, UKCRC CTU statisticians, industry statisticians, MHRA representatives and journal editors.

Candidates with a strong quantitative background are sought for this studentship (e.g. MSc in Medical Statistics or similar quantitative subject). Experience working in clinical trials is desirable.

HOW TO APPLY

You are applying for a PhD studentship from the MRC TMRP DTP. A list of potential projects and the application form is available online at:

http://www.methodologyhubs.mrc.ac.uk/about/tmrp-doctoral-training-partnership/

Please complete the form fully. Incomplete forms will not be considered. CVs will not be accepted for this scheme.

Please apply giving details for your first choice project. You can provide details of up to two other TMRP DTP projects you may be interested in at section B of the application form.

Before making an application, applicants should contact the project primary supervisor to find out more about the project and to discuss their interests in the research.

The deadline for applications is 4pm (GMT) 18 February 2022. Late applications will not be considered.

Completed application forms must be returned to: [Email Address Removed]

Informal enquiries may be made to [Email Address Removed]


Funding Notes

Studentships are funded by the Medical Research Council (MRC) for 3 years. Funding will cover tuition fees at the UK rate only, a Research Training and Support Grant (RTSG) and stipend (stipend to include London Weighting where appropriate). We aim to support the most outstanding applicants from outside the UK and are able to offer a limited number of bursaries that will enable full studentships to be awarded to international applicants. These full studentships will only be awarded to exceptional quality candidates, due to the competitive nature of this scheme.

References

Cornelius et al. Pain 2013. Phillips et al. BMC Medical Research Methodology 2020.
Mayo-Wilson et al. Trials 2019.
Stegherr et al. Biometrical Journal 2020.
Unkel et al. Pharmaceutical Statistics 2019.
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