The 'Molecularly Unstratified' Patient

Research exploring the moral, psycho-social, and societal significance of patients who are not eligible for specific forms of precision medicine. 

The molecularly unstratified patient: a focus for moral, psycho-social and societal research

Research question

In addition to the scientific and clinical significance of the application of a personalised (precision/stratified) medicine approach in cancer for patients who come to be ‘molecularly unstratified’ and who therefore will not be assigned to receive a novel treatment, what moral, psycho-social and societal issues are important in relation to such patients and how might they be best addressed?

Key publication

The 'molecularly unstratified patient': a focus for moral, psycho-social and societal research

Research Team

Prof Tim Maughan, University of Oxford

Prof Joshua Hordern, University of Oxford Healthcare Values Partnership

Prof Mark Lawler, Queen’s University Belfast

Prof Richard Sullivan, KCL

Dr Therese Feiler, University of Oxford Healthcare Values Partnership

Contributing partners

Deborah Alsina, Bowel Cancer UK

Dr Alison Hall, PHG Foundation

Prof Rob Horne, Centre for the Advancement of Sustainable Medical Innovation, UCL

Dr Liz Morrell, Centre for the Advancement of Sustainable Medical Innovation, University of Oxford

Alastair Kent, Rare Disease UK/Genetic Alliance UK


The promise

The zeitgeist of contemporary medicine has been built on the promise of personalised, precision medicine that utilises the newest tools of the biomedical revolution and the newest targeted treatments. Nowhere is this modern biomedical paradigm being more acutely realised and promised than in cancer care. The public discourse is fed, daily, with the fuel of this promise; new precision medicines and other biomarkers, and new discoveries in the fundamental aspects of molecular biology.

Clinical status

The clinical significance of being “molecularly unstratified” is that hope laden therapeutic options are closed down and allocation to non-targeted or standard therapeutic treatments, or supportive care become the only path. Those without the distinction of molecular specificity are excluded from eligibility to many targeted therapy trials (e.g. the 100 patients randomised in FOCUS4-N spread across many hospitals in the UK). While becoming unstratified may be due in some instances to technical failure of the assays or inadequate tumour content in the biopsy, more importantly, it can also be due to a lack of knowledge of how to target the tumour’s molecular characteristics in these specific patients. This lack of knowledge can make this group a focus for further research. However, this is increasingly challenging since it is significantly easier to identify therapeutic approaches within biomarker defined cohorts where a number of treatments have been developed compared to the challenges of for instance Ras mutant or Myc amplified tumours, where no therapeutic approach has been established. 

Left behind

Therefore, for the unclassified/unstratified patient, what remains is a speculative search for genetic or other disease drivers. This process is much further back in the developmental pathway when compared to current therapeutic intervention, implying many years or decades of waiting before a therapeutic treatment could emerge. While precision is being aimed at and yet not (or not yet) being delivered upon for these patients, what moral, societal, psychosocial issues attend the molecularly unstratified experience?

Psycho-social impact

Deflation of hope among and the difficulty of identifying next treatment steps for this group of persons may have the side-effect of a kind of psycho-social distinction between unclassified persons and those ‘lucky’ enough to be stratified in some way. This is important because such a distinction could become a widespread, quite self-conscious experience in society as the expectation of personalised precision, powered by a heady mix of clinical and scientific promise and hype, seems likely to become increasingly part of public and patient experiences. If researchers fail to address this experience of being a ‘molecularly unstratified’ person/patient as an issue requiring moral analysis and research focus, a dilution or at least pronounced heterogeneity in the public’s welcome of stratified/personalised approaches may follow.

Approaching the issue

To further specify and begin to clarify and address these issues, this project will draw on relevant social scientific approaches and humanities disciplines. Philosophical and theological approaches will consider moral questions which arise concerning the patients for whom the particular molecular nature of their cancer becomes the occasion of both feeling and being left out and left behind, bobbing untidily about in the wake of technological and scientific ‘advance’. While cancer is the focus in this study, this approach may also be applicable in other diseases beyond cancer e.g. in other MRC Stratified Medicine Consortia.

A preliminary workshop to explore this theme took place in Oxford on September 6th 2017.

A public workshop to discuss this research was held on November 29th 2017 at the European Alliance on Personalised Medicine inaugural European Personalised Health Congress entitled "Personalising your Health: A Global Imperative" at the Waterfront Conference venue in Belfast 27-30 November 2017. Event details.

To express interest in participating in the project, please contact Joshua Hordern