The market access of complementary diagnostics, precision medicine reimbursement policies and value assessment

Abstract

Precision medicine relies on two technologies jointly working together to deliver benefit to patients, a medicine on the one hand and a diagnostic on the other. The diagnostic's purpose is to identify the right patient population for the medicine, and could be considered complementary to the use of the medicine. In recent years the market access of these complementary diagnostics has been scrutinized as being inadequate to ensure time access for patients. This thesis has delved into this issue and, as indicated in Chapters 1 and 2, sought to gain insights in these market access hurdles and gain a better understanding of the value derived from complementary diagnostics for our healthcare system. Chapter 3 delves into the reimbursement policies of complementary diagnostics (such as companion diagnostics). It identifies the reasons why the reimbursement issues of complementary diagnostics, and specifically companion diagnostics have emerged across European countries. In this study several issues with the standard in vitro diagnostic reimbursement pathways were identified across eight European countries, that consequently have risen to prominence when precision medicine was gradually introduced into healthcare systems. Several alternative reimbursement approaches were identified, specifically for companion diagnostics in Germany and Belgium and more broadly for complementary diagnostics in France. Chapter 4 examines the Belgian healthcare payer's health technology assessment of precision medicines with companion diagnostics. This research formulated several recommendations that could enhance the assessment practice under the novel reimbursement pathway for precision medicines with companion diagnostics in Belgium, as identified and discussed in chapter 3. Specifically, the introduction of the linked-evidence approach was recommended to be introduced in the assessment practice as many companion diagnostics lack the necessary direct evidence to establish their clinical utility. In Chapter 5, a study on the interaction between the biomarker that is identified by the diagnostic test, and the precision medicine is discussed. This interaction can also be referred to as the 'precision mechanism'. In this chapter we introduce the use of a novel performance parameter that examines directly what is at the heart of precision medicine; The ability of the diagnostic test to identify patients who are more likely to respond to treatment. These novel parameters convey the probability that a patient belonging to a specific subgroup will benefit from precision therapy or not. We applied these novel parameters to European medicine agency's approved precision medicines. The result of this analysis shows that not every companion diagnostics, or therefore precision mechanism, provides the same clinical utility, and that this differentiation could inform reimbursement decision making. Chapter 6 covers a systematic review on the use and adoption of assessment frameworks for complementary diagnostics such as omics technologies, by health technology assessment agencies. Many of these frameworks have been published, however none have seen their wide scale adoption by health technology assessment agencies. When looking at the health technology assessment reports on these technologies, the most recurrent elements under assessment were the clinical utility and the cost-effectiveness of these types of tests. Concepts such as ethical, social, and organisational aspect were often not considered. Specifically for organisational aspects, this could be of concern, as the specific context in which a test is implemented determines its clinical utility and therefore its cost-effectiveness. In Chapter 7 this issue is further illustrated. The working hypothesis of the study is that specific contextual factors influencing the clinical utility of a test (e.g., level of training by the treating physician, local clinical guidelines, experience level, etc) will therefore influence the cost-effectiveness, and hence the value perception of the test, which is expressed through the value-based price at a certain willingness to pay threshold. The study collected a range of published clinical utility scenarios across countries and healthcare systems. These scenarios were consequently inputted into a cost-effectiveness model with all other variables kept the same. The results showed that there is a range of outcomes where either the test can be seen as extremely valuable to the current clinical practice and others where the test adds not much additional benefit tot the current practice. This finding has its implications if one is to consider value-based pricing mechanisms as a pricing methodology for complementary diagnostics. In summary, this work took a closer look at the policies forming the market access of complementary diagnostics together with a specific focus on their clinical utility, how it is established, how it can be interpretated through probabilistic performance parameters, how its interpretation has implications for reimbursement policies and finally how contextual factors determining the clinical utility influence the value perception of these tests.