Personalised and Precision Medicine in Cancer Clinical Trials: Panacea for Progress or Pandora's Box?

Abstract

Cancer clinical trials have been one of the key foundations for significant advances in oncology. However, there is a clear recognition within the academic, care delivery and pharmaceutical/biotech communities that our current model of clinical trial discovery and development is no longer fit for purpose. Delivering transformative cancer care should increasingly be our mantra, rather than maintaining the status quo of, at best, the often miniscule incremental benefits that are observed with many current clinical trials. As we enter the era of precision medicine for personalised cancer care (precision and personalised medicine), it is important that we capture and utilise our greater understanding of the biology of disease to drive innovative approaches in clinical trial design and implementation that can lead to a step change in cancer care delivery. A number of advances have been practice changing (e.g. imatinib mesylate in chronic myeloid leukaemia, Herceptin in erb-B2-positive breast cancer), and increasingly we are seeing the promise of a number of newer approaches, particularly in diseases like lung cancer and melanoma. Targeting immune checkpoints has recently yielded some highly promising results. New algorithms that maximise the effectiveness of clinical trials, through for example a multi-stage, multi-arm type design are increasingly gaining traction. However, our enthusiasm for the undoubted advances that have been achieved are being tempered by a realisation that these new approaches may have significant cost implications. This article will address these competing issues, mainly from a European perspective, highlight the problems and challenges to healthcare systems and suggest potential solutions that will ensure that the cost/value rubicon is addressed in a way that allows stakeholders to work together to deliver optimal cost-effective cancer care, the benefits of which can be transferred directly to our patients.

A systematic review and checklist presenting the main challenges for health economic modeling in personalized medicine: towards implementing patient-level models

“…A positive score in challenges [8][9][10] indicates that the authors identified the corresponding challenge and reported on the challenge in the publication. Negative scores indicate that the corresponding challenge is not addressed or identified and reported by the authors.…”

“…For instance, the use of randomized controlled trials (RCTs) for collecting evidence, and to inform health economic evaluations, is increasingly being questioned in a PM context [5][6][7][8][9]. RCTs are designed to draw conclusions on a population-level, while PM focusses on patient-level outcomes.…”

Mathematical and Computational Modeling in Complex Biological Systems

“…Kim et al proposed an ODE-based computational framework to implement virtual phase i trials in cancer, using an experimentally calibrated mathematical model of melanoma combination therapy, which can readily capture observed heterogeneous clinical outcomes and be used to optimize clinical trial design [120]. Lawler et al suggested potential solutions in precision medicine for clinical trial design that balanced the cost and value, to deliver cost-effective cancer care [121]. The benefits of Lawler's approach can be transferred directly to the patients [121].…”

“…Lawler et al suggested potential solutions in precision medicine for clinical trial design that balanced the cost and value, to deliver cost-effective cancer care [121]. The benefits of Lawler's approach can be transferred directly to the patients [121]. …”

Access for All: A Personalised Approach

“…Lawler and Sullivan [2] highlight the need to address the cost-value dilemma in PCM, moving beyond a simplistic ‘what the market can bear' approach to a more nuanced value-based pricing philosophy. Employing this approach and embedding this philosophy into cancer care pathways can help reward innovation that has truly transformative potential (as opposed to the marginal ‘me too' mentality that is potentially reducing therapeutic effectiveness in cancer clinical trials) [3] and allow the benefits of a value-centred PCM strategy to accrue for both patients and societies.…”