Clinical FeaturesOncology

Understanding the Health Economics of Colorectal Cancer: A COLOSSAL undertaking

Written by Dr Jonathan Briody. Dr Briody is a health economist conducting an economic evaluation of the cost-effectiveness of precision medicine for metastatic colorectal cancer (mCRC) at RCSI University of Medicine and Health Sciences

Colorectal cancer (CRC), sometimes referred to as bowel cancer, colon cancer, or rectal cancer, is the development of cells which grow out of control in the colon or rectum (parts of the large intestine). As the third most commonly diagnosed, and second deadliest cancer, on average 10% of cancer diagnoses and 9.4% of deaths are attributed to CRC annually. A global burden of 1.93 million new diagnoses and 0.94 million deaths in 2020, coupled with projections of 3.2 million annual cases in 2040, suggests a growing global public health challenge. A key determinant of patient prognosis, metastatic colorectal cancer (mCRC) accounts for most recorded colorectal cancer-related deaths. CRC cells may break away from the original tumour and travel to other parts of the body via the blood or lymphatic system. Typical locations for this CRC metastasis include the liver, lungs, and brain.

mCRC is a heterogeneous disease, and subtyping captures the significance of this heterogeneity in predicting clinical outcomes, such as expected therapeutic response and patient survival. At least half of mCRC cases have disruptions in the RAS gene, a gene which manages cell growth and division. Such disruptions lead to uncontrolled growth, making cells cancerous as they stop responding to the natural defences of the body. Microsatellite stable or MSS RAS mutant metastatic CRC cells additionally have a repair mechanism to address mutations in genes. While such mutational status currently does not significantly alter the initial treatment of mCRC from the frontline treatment traditionally provided in colorectal cancer, there is a growing consensus that targetted therapies may pose an important step in reducing mortality, and improving prognosis in mCRC.

COLOSSUS is an EU-funded Horizon 2020 project of 14 different partner organisations from 8 different countries that aims to provide more effective ways to index patients with mCRC and to develop subtypespecific treatment options for these patients. As part of this work, the consortium is analysing colorectal tissue and blood samples from MSS RAS mt mCRC patients in Spain, Germany and Ireland. Colossus has identified new methods for classifying mCRC via advanced multi-omic computational and mathematical modelling. These approaches have been applied to discover new MSS RAS mt specific subtypes, with contemporary clinically applicable diagnostic test prototypes in progress to stratify these patients. Now, specific novel combinatorial treatment options are under development based on these new classifications.

Appropriately establishing predictive biomarkers with targeted therapy options is not, however, the only step required for adoption in the clinic. With greater than 5 million people worldwide estimated to be living with Colorectal cancer, efforts to expand treatment options for mCRC are expected to have a significant impact on healthcare costs. Against a background of increasing demands on limited resources, the financial consequences of novel therapies are quickly becoming an important consideration in clinical decision-making.

Health economics exists to analyse whether interventions in health are both effective, and an efficient use of strained resources. However, health economics is about more than just money. Healthcare budgets are finite; investments in one area of the healthcare system will necessarily be at the expense of others. For example, given a national recommendation to increase cardiac screening, careful thought is needed on whether providing this additional service may require contracting other areas of care, and whether such shifts will lead to a net gain or loss in the total health produced in the current system. This discipline facilitates optimal decision making by providing a clear framework in which options that maximise the expected overall benefits from available resources in the health system are preferred. Particularly, economic evaluation relates the expected costs and benefits of alternative means of health care, such that it is possible to determine whether the gains from introducing an intervention outweigh those foregone when reallocating existing health budgets.

This basic principle of health economics, the production of the maximum level of net health available in the health care system, is the cornerstone of the economic evaluation of any new screening strategy, model of care or medical therapy – such as the delivery of a personalised medicine approach for patients with MSS RAS mt mCRC. In COLOSSUS, clinically relevant outcomes, such as improved patient survival, are of significant interest. However, the health economics of the proposed treatment strategy, when compared to current best practice, is also considered meaningful and explicitly modelled to estimate whether increments in expected benefit justify proposed shifts in resource allocation.

In this project, the cost per quality adjusted life-year (QALY) gained from testing and associated novel subtype-specific treatment options, compared with standard of care without testing, is estimated in a cost-effectiveness analysis. Cost-effectiveness analysis takes it’s name from the manner in which the benefit of the proposed intervention is measured, typically valuing outcomes in terms of natural units, such as deaths prevented or life years gained from one treatment when compared to another. When making choices on allocating resources to a new method of care, it is necessary to understand how much this intervention may cost (per unit of health gained) when compared with possible alternatives and whether this choice may lead to a net loss or gain in the total level of health currently produced in the health care system.

The results of such an analysis can thus be useful to decision makers, such as a national health authority, who will be able to identify interventions which will be more effective and less costly. In such cases, the proposed intervention will result in improvements in health and savings in resources – which can be redirected back into the health care system. Even when interventions are more costly than the existing standard of care, the health economic analysis provides a transparent structure to determine when health improvements warrant increased demands on health care services.

Particularly, the use of a common measure of outcome facilitates comparisons across every disparate healthcare sector. For example, as the most popular outcome studied in cost effectiveness analysis, the QALY simultaneously captures both elements of health, increased life expectancy and the health related quality of this increased expectancy. By it’s nature, a QALY gained in neonatal care has equal merit to one gained in rehabilitation interventions for the ageing. Consequently, it is possible in health economic evaluation for decision makers to establish allocative efficiency, that is, to make decisions to maximise the health of society as a whole.

Whilst the design of more targeted and personalised regimens is something which is welcomed in mCRC, in the provision of health care, difficult choices are inevitable. The discipline of health economics provides a framework to make such decisions equitable and explicit. To support real world advancements in patient care at all stages, from the bench to the bedside, COLOSSUS is embracing a robust analysis of the expected clinical effectiveness and the cost-effectiveness of its proposed personalised medicine approach for patients with MSS RAS mt mCRC.

For further information on the COLOSSUS project, please visit or follow COLOSSUSEU on Facebook and Twitter. Dr Briody can be found at: @JonathanBriody

This project has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No 754923. The material presented and views expressed here are the responsibility of the author(s) only. The EU Commission takes no responsibility for any use made of the information set out.

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