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UCL Institute of Clinical Trials and Methodology

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Current studentships

MRC Clinical Trials Unit Funded Studentships

Funding is also available for the following studentships based at MRCCTU starting from Autumn 2022.  These UKRI-funded PhD studentships, will be available to award for successful applicants across the following projects:

Second line antiretroviral therapy in infants, children and adolescents living with HIV

What is the Project?

The growing numbers of HIV-infected children on first-line antiretroviral therapy (ART), coupled with widening coverage of viral load monitoring leading to increased detection of first-line treatment failure, means increasing numbers of children are switching to second-line ART. MRC CTU has conducted two large randomised controlled trials evaluating different treatment regimens for children starting second-line ART.

 The ODYSSEY trial recruited ~800 children starting first or second line ART in Africa, Thailand and Europe. Children were randomised to dolutegravir-based ART versus standard of care and followed up for over 2 years. Around 400 participants started second-line ART at entry to ODYSSEY. ODYSSEY reported superiority of dolutegravir-based ART in the total trial population. The CHAPAS-4 trial recruited over 900 children starting second line ART in Africa. Children were randomised to dolutegravir- versus darunavir- versus azatanavir- versus lopinavir-based ART; all children will complete follow-up by February 2023 and no results are available yet.

This PhD offers the opportunity to combine data across the two trials to answer clinically important questions, for example:

1.         What is the efficacy and safety of dolutegravir-based ART versus atazanavir or lopinavir-based ART in children starting second-line therapy?

2.         Can we identify predictors of poor virological outcomes on second-line doutegravir-based ART in children?

3.         Is there an association between drug resistance at switch to second-line ART, NRTI-backbone and subsequent treatment failure in children starting second-line dolutegravir-based ART?

4.         What is the evidence from ODYSSEY and CHAPAS-4 regarding outcomes for children who start third-line treatment?

Depending on the interests and background of the student there will also be the opportunity for more methodological work within the project.

Who are the ICTM and the MRC Clinical Trials Unit at UCL?

The MRC CTU at UCL is at the forefront of resolving internationally important questions in infectious diseases and cancer, and delivering swifter and more effective translation of scientific research into patient benefits. It does this by carrying out challenging and innovative studies, and developing and implementing methodological advances in study design, conduct and analysis.  You will be joining a team of renowned experts in the field of clinical trials.

Eligibility

Ideally, the candidate should have a strong background in statistics, ideally with an MSc in Applied Statistics or Medical statistics. Nb We are only able to consider a full-time student for this project, due to timelines for completing some of the proposed work.

How to Apply & Additional Information

Who are the supervisors?

Dr Debbie Ford will be the primary supervisor.  You will also be supported by secondary supervisors and a Thesis Committee (TC), which will provide degree-spanning support and advice about academic and training progress for the successful candidate over the course of the Doctoral study.

When can I start?

Successful candidates are expected to commence studies in October 2022

What funding is available?

A full-time studentship in line with the current UKRI PhD studentship levels, including home (UK) student fees and stipend.  Successful overseas candidates may also be eligible for top-up funding to cover overseas student fees.

How do I apply?

We would encourage you to speak to Dr Ford (email: debbie.ford@ucl.ac.uk) in the first instance for further information. Applications by CV and covering letter should be sent to ICTM.education@ucl.ac.uk

Deadline for applications: 14 March 2022. 

Estimands for interventions which may be used more than once: implications for design and analysis of clinical trials

What is the Project?

In practice, many interventions may be used more than once. For instance, IVF treatment may be given again if the first cycle is unsuccessful; patients may become re-infected with certain diseases, requiring re-treatment; or patients may suffer an underlying condition such as sickle cell disease which causes repeated pain episodes, each require a new round of treatment to manage. These interventions are typically evaluated using a parallel group design, where only the first treatment administration is tested, however this approach may not be sufficient to fully inform the intervention’s use in practice, as the treatment may become less effective the more often it is used, or may work differently in those who require treatment more often.

This project aims to define relevant estimands for such multi-use interventions; evaluate a number of novel trial designs (including re-randomisation, and cluster designs) using simulation and re-analysis of published datasets to identify which are most appropriate in this setting; and evaluate different methods of analysis (independence estimating equations, mixed-effects models, generalised estimating equations) using a combination of simulation and re-analysis of published datasets to determine which are best.

Who are the ICTM and the MRC Clinical Trials Unit at UCL?

The MRC CTU at UCL is at the forefront of resolving internationally important questions in infectious diseases and cancer, and delivering swifter and more effective translation of scientific research into patient benefits. It does this by carrying out challenging and innovative studies, and developing and implementing methodological advances in study design, conduct and analysis.  You will be joining a team of renowned experts in the field of clinical trials.

Eligibility

Ideally, the candidate should have a strong background in mathematics and ideally hold an MSc in Statistics or similar.  Candidates should also have a keen interest in clinical trials methodology.

How to apply & Additional Information

Who are the supervisors?

The supervisory teams is Professor James Carpenter and Dr Brennan Kahan.  You will also be supported by a Thesis Committee (TC), which will provide degree-spanning support and advice about academic and training progress for the successful candidate over the course of the Doctoral study.

When can I start?

Successful candidates are expected to commence studies in October 2022

What funding is available?

What funding is available? A full-time studentship in line with the current UKRI PhD studentship levels, including home (UK) student fees and stipend.  Successful overseas candidates may also be eligible for top-up funding to cover overseas student fees.

How do I apply?

We would encourage you to speak to Dr Brennan Kahan (email: b.kahan@ucl.ac.uk) in the first instance for further information. Applications by CV and covering letter should be sent to ICTM.education@ucl.ac.uk

Deadline for applications: 14 March 2022. 

 Design and analysis of trials with multiple primary outcomes

What is the project?

Trials are typically conducted with one primary outcome, often because there is a paramount measure of patient’s health such as survival, but sometimes only for simplicity without a good scientific reason. This then leads to a simple decision rule for whether to declare a new treatment better than the standard at the end of a trial: if its performance on the primary outcome is significantly better (p<0.025 in one-tailed test). However even in trials with ostensibly one primary outcome a treatment will often not be declared better than standard if it has a harmful effect on other ‘safety’ outcomes. This need to include outcomes to measure other effects beyond the primary outcome in making a decision about treatment is particularly apparent in non-inferiority trials where treatments are often trialled precisely because they are thought to reduce ‘harms’ from treatment. Another area where single primary outcomes are problematic is trials of complex interventions which are common in global health and are typically expected to impact on multiple important dimensions of health in different ways. Specifying just one primary outcome is illogical and risks drawing the wrong conclusion - missing the important benefit of an intervention on other outcomes or declaring an intervention a success when it is beneficial for the primary outcome but harmful for others. Selecting a decision rule based on multiple primary outcomes that is scientifically meaningful and also preserves the ‘type I error rate’ is more complex.

The aim of this PhD is to explore how best to analyse and interpret the results of trials with multiple primary outcomes using a range of examples, and explore the implications for trial design by:  

  • Reviewing existing methods for handling multiple primary outcomes and the corresponding decision rules for declaring the new treatment better than the standard.
  • Considering how these methods would apply to example trials including:

•     The BLISTER trial, a noninferiority trial in the treatment of bullous pemphigoid (in which poorer treatment outcomes need to be traded off against reduced side-effects)

•     The AFYA trial of an intervention in Kenya hoped to improve antenatal clinic attendance, delivery at a health centre, postnatal clinic attendance and infant vaccination (and expected to have a similar effect on all)

•     A trial of an intervention for adolescents in India hoped to improve mental health, school attendance and dietary diversity (not expected to have a similar effect on all)

  •  Examining the method proposed by Donkers et al (J Clin Epi 2017 81:86-95) for two primary outcomes and how it might be extended to several outcomes  

Outcomes of this PhD should include: 

  •  Providing guidance on choice of most appropriate decision rule to handle multiple primary outcomes according to trial characteristics and objectives and develop methodology on how to test under each rule whether the new treatment is better than standard preserving the type I error rate. 
  • Developing methodology for sample size calculation with multiple primary outcomes, illustrating its use for example trials, and investigating its performance. 
Who are the ICTM and the MRC Clinical Trials Unit at UCL?

The MRC CTU at UCL is at the forefront of resolving internationally important questions in infectious diseases and cancer, and delivering swifter and more effective translation of scientific research into patient benefits. It does this by carrying out challenging and innovative studies, and developing and implementing methodological advances in study design, conduct and analysis.  You will be joining a team of renowned experts in the field of clinical trials.

Eligibility

Ideally, the candidate would hold a Masters level qualification in medical statistics or a closely aligned area, or have equivalent experience with a strong mathematical background. 

How to apply & Additional Information

Who are the supervisors?

The supervisory team includes Professor Andrew Copas, MRC CTU at UCL, and the supervisory team will include Professor Rumana Omar from PRIMENT CTU at UCL.  You will also be supported by members of the noninferiority trials methodology group at MRC CTU (which the student will join) and a Thesis Committee (TC), which will provide degree-spanning support and advice about academic and training progress for the successful candidate over the course of the Doctoral study.

When can I start?

Successful candidates are expected to commence studies in October 2022

What funding is available?

What funding is available? A full-time studentship in line with the current UKRI PhD studentship levels, including home (UK) student fees and stipend.  Successful overseas candidates may also be eligible for top-up funding to cover overseas student fees.

How do I apply?

We would encourage you to speak to Professor Copas (email: Andrew.copas@ucl.ac.uk) in the first instance for further information. Applications by CV and covering letter should be sent to ICTM.education@ucl.ac.uk

Deadline for applications: 14 March 2022.   

Methods for incorporating complex trial designs into meta-analysis 

What is the Project?

The landscape of randomised trials is becoming more complex, with platforms, baskets, cross-over and adaptive-randomisation features all gaining in popularity and use. Efforts to increase efficiency in identifying effective interventions for COVID-19 has further contributed to their accelerated uptake. Although novel designs have clear advantages for individual trials, the implications for meta-analysis are unclear; in fact some current proposals from the evidence synthesis community may essentially penalise complex trials for efficient revision of timelines.

The main aim of this PhD is to establish methods for appropriately incorporating aggregate data into meta-analysis from a variety of complex trial designs; and to identify the implications of such designs from a trial-specific perspective when it comes to reporting or sharing data for the purpose of meta-analysis. This PhD will focus on pairwise aggregate data meta-analyses, but extensions to individual participant data (IPD) and/or network meta-analysis may also be appropriate. The project will include the following pieces of work:

  • A review of existing literature on the topic of evidence synthesis in the presence of complex trial designs or features, such as the following:

    • Platform designs, including multi-arm multi-stage (MAMS) and adaptive-randomisation trials
    • Factorial, stepped-wedge and cross-over trials
    • Trials designed to test hypotheses of non-inferiority
    • Use of Bayesian vs frequentist frameworks
  • Identification of specific issues or unanswered questions, based on literature review and through engagement with members of the clinical trial and meta-analysis community
  • Development of mathematical (or other) approaches to tackle these questions, including practical guidance or tools, and/or statistical code
  • Assessing the practicality and statistical performance of these approaches, both using empirical data from meta-analysis datasets housed at MRC CTU at UCL, and through simulation studies
  • Development of guidance and recommendations both for practitioners of future meta-analyses, and for reporting and sharing of aggregate data from trials with complex designs, with consideration of existing guidance such as CONSORT and PRISMA
Who are the ICTM and the MRC Clinical Trials Unit at UCL?

The MRC CTU at UCL is at the forefront of resolving internationally important questions in infectious diseases and cancer, and delivering swifter and more effective translation of scientific research into patient benefits. It does this by carrying out challenging and innovative studies, and developing and implementing methodological advances in study design, conduct and analysis.  You will be joining a team of renowned experts in the field of clinical trials.

Eligibility

Ideally, the candidate would hold a Masters level qualification in medical statistics or a closely aligned area, or have equivalent experience with a strong mathematical background. 

How to apply & additional information

Who are the supervisors?

The supervisory team includes Dr Peter Godolphin and Mr David Fisher.  You will also be supported by a Thesis Committee (TC), which will provide degree-spanning support and advice about academic and training progress for the successful candidate over the course of the Doctoral study.

When can I start?

Successful candidates are expected to commence studies in October 2022.

What funding in avaliable?

What funding is available? A full-time studentship in line with the current UKRI PhD studentship levels, including home (UK) student fees and stipend.  Successful overseas candidates may also be eligible for top-up funding to cover overseas student fees.

How do I apply?

We would encourage you to speak to Dr Godolphin (email: peter.godolphin@ucl.ac.uk) or Mr Fisher (email: d.fisher@ucl.ac.uk) in the first instance for further information. Applications by CV and covering letter should be sent to ICTM.education@ucl.ac.uk

Deadline for applications: 14 March 2022. 

 Exploring methods for borrowing evidence across baskets or subgroups in a clinical trial

What is the project?

Basket designs are an innovative trial design used increasingly often in cancer trials to evaluate targeted therapies on related cancers in multiple locations. A basket trial is designed to study multiple patient subgroups (baskets): a single treatment is delivered to subgroups of patients with the same disease, aiming to draw conclusions about effectiveness within rather than across subgroups. Borrowing evidence across baskets can be beneficial in enabling conclusions to be drawn about effective treatments in rare diseases or small patient populations which could not be studied in a standalone clinical trial. The aim of this project is to explore methods for borrowing evidence across baskets or subgroups in a clinical trial, in order to provide guidance and recommendations for practice.

The project will address the following research questions:

  • When should we borrow evidence?
  • Where should we borrow evidence from?
  • How should we choose the degree of borrowing?
  • How should we assess our approach to borrowing evidence
  • How should basket trials be designed when we intend to borrow evidence? 
Who are the ICTM and the MRC Clinical Trials Unit at UCL?

The MRC CTU at UCL is at the forefront of resolving internationally important questions in infectious diseases and cancer, and delivering swifter and more effective translation of scientific research into patient benefits. It does this by carrying out challenging and innovative studies, and developing and implementing methodological advances in study design, conduct and analysis.  You will be joining a team of renowned experts in the field of clinical trials. 

Eligibility

Candidates should hold, or expect to achieve, an undergraduate degree in mathematics/statistics (upper second-class or first-class) and ideally a Masters degree in statistics or related subject.

How to apply & additional information

Who are the supervisors?

The supervisory team is Dr Becky Turner and Professor Ian White.  You will also be supported by a Thesis Committee (TC), which will provide degree-spanning support and advice about academic and training progress for the successful candidate over the course of the Doctoral study.

When can I start?

Successful candidates are expected to commence studies in October 2022

What funding is available?

What funding is available? A full-time studentship in line with the current UKRI PhD studentship levels, including home (UK) student fees and stipend.  Successful overseas candidates may also be eligible for top-up funding to cover overseas student fees.

How do I apply?

We would encourage you to speak to Dr Becky Turner (email: becky.turner@ucl.ac.uk) in the first instance for further information. Applications by CV and covering letter should be sent to ICTM.education@ucl.ac.uk

Deadline for applications: 14 March 2022. 

Entry requirements