Evaluating the impact of advancements in myeloma treatment integrating clinical trial and real-world data

One full scholarship is available in the Leeds Institute of Clinical Trials Research in the School of Medicine in 2024/25. <br /> <br /> This scholarship is open to UK applicants and covers fees plus £19,237 maintenance. This fully funded PhD place provides an exciting opportunity to pursue postgraduate research in cancer clinical trials methodology within the Leeds Cancer Research UK Clinical Trials Unit at the Leeds Institute of Clinical Trials Research. The Institute is an international leader in the field of clinical trials and the CRUK Unit is one of the largest in the UK being one of only 7 clinical trials units to receive a prestigious infrastructure award from Cancer Research UK. We conduct national and international early phase and late phase clinical trials specialising in blood cancers, treatment with radiotherapy, and colorectal cancer, and this PhD will integrate into these portfolios. <br /> <br /> We invite applications from prospective postgraduate researchers who wish to commence study for a PhD in the academic year 2024/25 for the CRUK Clinical Trials Unit Scholarship. The award is open to full-time or part-time candidates (UK only) who meet the eligibility for a place on a PhD degree at the School of Medicine.

<h5>Background</h5> <p>Evidence from the concurrent series of MRC/NRCI clinical trials in new diagnosed multiple myeloma patients since 1980 have shown that outcomes have greatly improved over time [1]. Randomised controlled trials (RCT) and observational studies based on routinely collected health data are complementary sources of information that can be used to quantify the impact of changes in treatment over time. Strict includsion and exclusion criteria of RCTs often mean trial participants are not representative of the wider population. In real-world populations new treatments may not be reflective of clinical standards of care where the dose of individual drugs may be adjusted according to patient factors such as comorbidities, frailty and disease complications. It is important to know how the improvements in outcomes in trial populations translates to improvements in real world cohorts.</p> <p>A range of different measures and metrics to describe survival trends exist, including both relative and absolute measures. These are important for clinicians and patients to help understand the impacts of a cancer diagnosis and treatment on a patient’s prognosis. However, different metrics of interest are years of life lost (YLL) and (statistical) cure. YLL encompasses a range of different definitions and methodologies, with each method focused on estimating different quantities [2]. YLL metrics are popular and simple summary measures to describe a population’s health in relation to a diagnosis of cancer. Statistical cure model can provide additional insights into survival trends by assuming there are two groups of patients: one who do not experience the outcome of interest and are ‘cured’ and the other who do experience the outcome (the ‘uncured’) and their survival is estimated separately [3-5]. These alternative metrics may be better suited to inform patients and clinicans of prognosis following a cancer diagnosis and assessing impact.</p> <h5>Studentship</h5> <p>This project will assess the impact of improvements in myeloma treatment in both clinical trials and population-based (real world setting) by evaluating and implementing suitable metrics to convey impact.  The project will involve a variety of descriptive, epidemiological and survival modelling techniques utilising data from different data sources including national phase 3 clinical trials, regional and national cancer registry data.</p> <p>The project will review methodology to estimate standard metrics for cancer survival (including YLL and cure models) and assess which are most suitable to evaluate impact in both trial and real-world populations.  The application of these methods can be developed and applied to the different datasets to assess if it is possible to translate the trial findings in real world data and how these vary by patient and tumour characteristics. The project will assess myeloma outcomes initially but there may be potential to expand to consider other haematological cancers.</p> <h5>Supervisors</h5> <p>Day-to-day support will be provided by Professor David Cairns and Dr Lesley Smith of the Leeds Cancer Research UK Clinical Trials Unit, with expertise in the development and implementation of statistical methods in clinical trials and routine data. Co-supervision will be provided by Dr Alex Smith from Haematological Malignancy Research Network, University of York, with expertise in epidemiology.</p> <h5>References</h5> <ol> <li>Cairns D, Gregory W, Dunn J, Iqbal G, MacLennan I, Rawstron A, et al. From Plateau to MRD-Negative CR: Outcomes in the MRC/NCRI Series of Randomised Trials in Newly Diagnosed Patients With Multiple Myeloma From 1980 to 2016. Clin Lymphoma Myeloma Leuk 2017;17. <a href="https://doi.org/10.1016/j.clml.2017.03.110">https://doi.org/10.1016/j.clml.2017.03.110</a>.</li> <li>Chudasma Y V, Khunti K, Gillies CL, Dhalwani NN, Davies Davies MJ, Yates T, et al. Estimates of years of life lost depended on the method used: tutorial and comparative investigation. J Clin Epidemiol 2022;150:42–50. <a href="https://doi.org/10.1016/j.jclinepi.2022.06.012">https://doi.org/10.1016/j.jclinepi.2022.06.012</a>.</li> <li>Yu XQ, De Angelis R, Andersson TML, Lambert PC, O’Connell DL, Dickman PW. Estimating the proportion cured of cancer: Some practical advice for users. Cancer Epidemiol 2013;37:836–42. <a href="https://doi.org/10.1016/j.canep.2013.08.014">https://doi.org/10.1016/j.canep.2013.08.014</a>.</li> <li>Othus M, Barlogie B, LeBlanc ML, Crowley JJ. Cure models as a useful statistical tool for analyzing survival. Clinical Cancer Research 2012;18:3731–6. <a href="https://doi.org/10.1158/1078-0432.CCR-11-2859">https://doi.org/10.1158/1078-0432.CCR-11-2859</a>.</li> <li>Ravi P, Kumar SK, Cerhan JR, Maurer MJ, Dingli D, Ansell SM, et al. Defining cure in multiple myeloma: A comparative study of outcomes of young individuals with myeloma and curable hematologic malignancies. Blood Cancer J 2018;8. <a href="https://doi.org/10.1038/s41408-018-0065-8">https://doi.org/10.1038/s41408-018-0065-8</a>.</li> </ol>

<p>To apply for this scholarship opportunity applicants should complete an <a href="http://www.leeds.ac.uk/research-applying/doc/applying-research-degrees">online application form</a> and attach the following documentation to support their application.</p> <ul> <li>a full academic CV</li> <li>degree certificate and transcripts of marks</li> <li>Evidence that you meet the University's minimum English language requirements (if applicable)</li> </ul> <p>To help us identify that you are applying for this scholarship project please ensure you provide the following information on your application form;</p> <ul> <li>Select PhD in Medicine as your programme of study</li> <li>Give the full project title and name the supervisors listed in this advert</li> <li>For source of funding please state you are applying for a CRUK CTU Scholarship </li> </ul> <p><strong>Please note there are 4 advertised projects for the 2 available awards. If you are interested in more than one project, please submit only one application and indicate your order of preference for the projects. </strong></p> <p>If English is not your first language, you must provide evidence that you meet the University's minimum English language requirements (below).</p> <p><em>As an international research-intensive university, we welcome students from all walks of life and from across the world. We foster an inclusive environment where all can flourish and prosper, and we are proud of our strong commitment to student education. Across all Faculties we are dedicated to diversifying our community and we welcome the unique contributions that individuals can bring, and particularly encourage applications from, but not limited to Black, Asian, people who belong to a minority ethnic community, people who identify as LGBT+ and people with disabilities. Applicants will always be selected based on merit and ability.</em></p>

Applicants to this scholarship in the School of Medicine should normally have an Undergraduate degree of 2:1 or above (or international equivalent) in a relevant subject area. A Master’s degree is desirable, but not essential.

The minimum English language entry requirement for postgraduate research study in the School of Medicine is an IELTS of 6.5 overall with at least 6.0 in each component (reading, writing, listening and speaking) or equivalent. The test must be dated within two years of the start date of the course in order to be valid.

<p>We are offering 2 full-time PhD scholarships in the Leeds Institute of Clinical Trials Research within the School of Medicine for two UK candidates, covering a maintenance grant matching UKRI maintenance stipend (£19,237 in 2024/25) and UK tuition fees for three years, subject to satisfactory progress. The award will be made for one year in the first instance and renewable for a further period of up to two years, subject to satisfactory academic progress.</p> <p>Other Conditions:</p> <ul> <li>Applicants must not have already been awarded or be currently studying for a doctoral degree</li> <li>Applicants must live within a reasonable distance of the University of Leeds whilst in receipt of this scholarship</li> </ul>

<p>For further information please contact the Faculty of Medicine and Health PGR Admissions team<br /> e: <a href="mailto:fmhpgradmissions@leeds.ac.uk">fmhpgradmissions@leeds.ac.uk</a></p>