Precision and Uncertainty : Cancer biomarkers and new perspectives on fairness in priority setting decisions in personalized medicine

Abstract

Introduction: Precision oncology aims to tailor diagnostics and treatment to patients’ individual biological characteristics, and a central part of this approach is the stratification of patients into smaller groups. This might increase treatment effect, avoid ineffective treatment and harmful side effects, and promote fair priority setting. But precision oncology may also increase uncertainty about the quality of evidence, creating public controversy and challenges for fair priority setting.

Objectives: The primary aim of this thesis was to describe and discuss how biomarkers and personalized medicine are being incorporated into priority setting decisions for new cancer drugs in Norway, and to explore how this may challenge concepts of fairness in the priority setting system. This was done by investigating three secondary aims, all with special attention to biomarkers: I) To describe the Norwegian system for priority setting and drug appraisal, and to analyse if coverage decisions are in accordance with the established criteria for priority setting; II) To study Norwegian cancer doctors’ stated preferences for considering individual patient characteristics in a hypothetical priority setting scenario; III) To provide a critical analysis of the current priority setting practice for personalized medicine through a perspective from science and technology studies.

Methods: Three studies were conducted to respond to each of the secondary objectives. Study I and II were empirical, while study III was a theoretical analysis. In study I we used logistic and linear regression analysis to evaluate drug coverage decision for the Norwegian specialized health care sector from 2014 to 2019, using confidential price data. In study II we distributed a survey to Norwegian cancer doctors where we used a conjoint analysis to elicit preferences in a hypothetical priority setting scenario between two cancer patients. In study III we examined and criticized the Norwegian priority setting practice through a Science and Technology perspective.

Results: Study I shows a strong inverse relationship between the incremental cost-effectiveness ratios and the probability of approval, after price negotiations and severity of disease has been taken into account. This demonstrates how cost-effectiveness, price negotiations and concerns for a fair distribution of health benefits are systematically implemented in the Norwegian drug appraisal system. This was also found for biomarker-accompanied cancer drugs; however, a systematic quantitative evaluation of uncertainty is not possible due to the lack of data.

Study II shows that biomarker status is perceived as relevant for priority setting decisions, alongside more well-known patient characteristics like age, physical function, and comorbidity. Based on these findings we discuss a framework that can help clarify whether biomarker status should be accepted as an ethically acceptable factor for stratifying patients into smaller groups and give them unequal treatment. In this framework a key aspect of reducing uncertainty is to improve biomarker quality.

In study III precision oncology is seen not only as a solution but also a potential contributor to high health care costs and persisting controversy. We argue that a wider perspective on science and society is needed to strengthen the priority setting system. From a co-production perspective, scientific, technological, and societal developments are causally entangled into each other. Alongside refining priority setting principles, one can and ought to raise normative questions about the trajectory of personalized cancer medicine and of how to create a well-functioning public sphere.

Conclusion: Precision oncology and cancer biomarkers appear to be well integrated in the priority setting system, but there are also concerns about how uncertainty increases and how this may challenge priority setting. Acknowledging the interdependence between science and society, this calls for a stronger emphasis on co-production of knowledge and procedural aspects of fairness. This could strengthen the priority setting system and reduce public controversy. A wider participation of stakeholders is essential, and deliberation must address both the production of knowledge and of standards. The former includes organization of trial design, research and development of new drugs, and even the whole political economy of drug development, and the latter the normative foundations of priority setting, its principles and practices. In such reimagining there is still a role for biomarkers, but their role would be reimagined too.