The AWARD criteria to guide the translation of liquid biopsies for use in cancer management
Professor Maarten IJzerman – lead of the Cancer Health Services Research unit at the University of Melbourne Centre for Cancer Research – has developed new criteria proposed to guide studies towards the routine implementation of liquid biopsies in addition to clinical research required to demonstrate clinical utility to improve cancer outcomes.
Maarten IJzerman, MSc, PhD
University of Melbourne Centre for Cancer Research
Sir Peter MacCallum Department of Medical Oncology
Parkville, Australia
Challenges in the clinical translation of liquid biopsies
Blood based liquid biopsies are considered a promising diagnostic and monitoring tool for cancer. Because liquid biopsies only require a blood draw, they are non-invasive, potentially more rapid and assumed to be a less costly alternative to genomic analysis of tissue-biopsies. In 2020, a multi-disciplinary workshop with nearly 100 Australian experts was organised to discuss challenges in the routine implementation of liquid biopsies in cancer management. A survey and real-time polls were used to collect experts’ opinions about the current evidence of clinical utility and the barriers to implementation. Clinical, laboratory and health economics presentations were given to illustrate the opportunities and current levels of evidence, followed by three moderated break-out sessions to discuss one of three applications, (1) early cancer detection, (2) minimal residual disease and (3) monitoring of progressive disease. The results of the workshop were published in January 2021 [1].
Technology lifecycle and management: early HTA to support reimbursement
The rapid development of genomics, including liquid biopsies, have led to an ongoing emphasis on how health systems should reimburse and provide those diagnostic services to patients. The debate usually focuses on the clinical benefit or utility relative to the additional cost of the assays. There is consensus that not just prognostic value but clinical utility, i.e. the ability to change clinical management and thus improve outcomes, should drive implementation and consequently the reimbursement. However, with ongoing developments in precision oncology, it becomes increasingly difficult to determine the clinical utility because of an increasing number of molecular targets, (combination) treatments and complexity in prescribing and monitoring response to treatment. Moreover, demonstration of clinical utility is a requirement, but it certainly does not ensure implementation and reimbursement.
Early Health Technology Assessment (also referred to as development-focussed or lifecycle HTA) is therefore proposed as a mechanism to quantify (uncertainties) in the health economic evidence base in cases where clinical evidence is either emerging or immature [2]. The use of early-stage modelling is an attractive and low-cost approach to informing the translation of, for instance, liquid biopsies. Only recently, early-stage economic modelling studies investigating the potential cost-effectiveness were published. To further guide the implementation and to improve early-stage health economic models, the AWARD criteria are presented during the Thomas Ashworth Symposium in 2021.
The AWARD criteria
The AWARD criteria are proposed to guide studies towards the routine implementation of liquid biopsies in addition to clinical research required to demonstrate clinical utility to improve cancer outcomes. Feedback and improvements are welcome at cancer-hsr@unimelb.edu.au.
| Criterion | What is important to consider? | |
|---|---|---|
| A | Agnostic vs. tumor specific | A tumor-informed assay, presenting detailed molecular information about the origin of the tumor, is preferred in particular for screening and because of the higher clinical utility in treatment selection. However, a tumor-agnostic test such as ctDNA volume or CTC enumeration is easier to implement because of the lower cost of the assay, economies of scale and advantages to integrate in the workflow. Tumor-agnostic assays may be considered as a triage test or cheap monitoring. |
| W | Workflow | How and when the liquid biopsy is to be used is critical as optimal use should align with the clinical workflow. For instance, knowing which mutations to monitor before or immediate after surgery can reduce the turn-around time for ctDNA analysis which is clinically relevant. Similar, the workflow and turn-around time in the pathology lab is reduced with if batch volumes increase. This has implications for offering services in low-resource or regional health settings. |
| A | Advancing clinical outcomes | Obviously, the clinical utility to improve patient outcomes (predictive and not just prognostic validity) is a key requirement for an assay. The assay should be able to inform about changes in management, whether that is the selection of systematic cancer treatments or a triage for further molecular imaging. |
| R | Reimbursable price of the assay | The cost of the assay should align with the benefits realised for patients and, in that instance, targeted (real-time PCR) assays at lower cost may be sufficient for monitoring of known molecular targets. |
| D | Downstream effects and flow-on consequences | For any molecular test it is important to consider the downstream effects (better treatment outcomes) and flow-on consequences (additional diagnostic testing). Liquid biopsies may have health economic impact in cancer surveillance, i.e. they are used to triage for imaging rather than routine imaging for all patients. Similar, if for treatment selection, the window of opportunity to improve survival using a liquid biopsy is largest early in the (progressive) disease informing 1st or 2nd line treatments. |
References
1.IJzerman MJ, de Boer J, Azad A, Degeling K, Geoghegan J, Hewitt C, Hollande F, Lee B, To YH, Tothill RW, Wright G, Tie J, Dawson SJ. Towards Routine Implementation of Liquid Biopsies in Cancer Management: It Is Always Too Early, until Suddenly It Is Too Late. Diagnostics. 2021 Jan 11;11(1):103. doi: 10.3390/diagnostics11010103
2.IJzerman MJ, Steuten LM. Early assessment of medical technologies to inform product development and market access: a review of methods and applications. Appl Health Econ Health Policy. 2011 Sep 1;9(5):331-47. doi: 10.2165/11593380-000000000-00000
3.To YH, Degeling K, Kosmider S, Wong R, Lee M, Dunn C, Gard G, Jalali A, Wong V, IJzerman M, Gibbs P, Tie J. Circulating Tumour DNA as a Potential Cost-Effective Biomarker to Reduce Adjuvant Chemotherapy Overtreatment in Stage II Colorectal Cancer. Pharmacoeconomics. 2021 Aug;39(8):953-964. doi: 10.1007/s40273-021-01047-0
Suggested citation
IJzerman MJ: The AWARD criteria: Criteria to consider when translating liquid biopsies for routine clinical cancer management. Keynote presented at the Thomas Ashworth Symposium (Sydney), 21/22 October 2021: https://www.liquidbiopsy.org.au