Biomarker testing using molecular diagnostics is one of the cores of precision oncology. By identifying targetable genomic alterations, physicians can identify patients who are more likely to respond to targeted therapies. Additionally, identification of prognostic biomarkers can predict long-term outcomes for individual patient whereas others can lead to improved diagnosis by refinements of initial diagnosis.
Today, there are many cancer-related biomarkers being evaluated within routine cancer care such as HER2, NTRK, BRAF, ALK and many more cancer-specific as well as pan-cancer are emerging. Many studies have shown that patients who are administered biomarker / molecularly matched therapies have better outcomes than the ones who received cytotoxic agents such as chemotherapies 1,2 .
However, bringing a novel molecular diagnostics-based biomarker testing tool (for which there is no comparable and reimbursed solution available) into Europe routine healthcare system is not so straight forward. From manufacturing and validating a novel assay until bringing into a routine testing setting, it can take more than a decade as brilliantly described in a recent publication by Denis Horgan et al3. where they describe the challenges faced by OncoTypeDx, a prognostic and predictive tool that amongst other was able to distinguish a subpopulation of breast cancer patients in which adjuvant chemotherapy was not beneficial, suggesting a significant clinical impact on patient’s quality of life. The long trajectory and some of the key events related to implementation of OncoTypeDx in routine testing are summarized in Figure 1.
Figure 1. Implementation trajectory of OncoTypeDx into routine care (from Horgan et al (3)).
Once the biomarker-related assay has gone through analytical and clinical validation as well as clinical and economical utility assessment, manufacturers need to engage with local health technology assessment (HTA) bodies and payers. HTA bodies play a crucial role in evaluating the clinical effectiveness and cost-effectiveness of new health technologies, including biomarker tests, to inform reimbursement decisions across EU. Examples of HTA bodies are National Institute for Health and Care Excellence (NICE) in UK, Zorginstituut Nederland or National Healthcare Institute in Netherlands, KCE (Kenniscentrum voor de Gezondheidszorg) or Belgian Health Care Knowledge Centre in Belgium and in Spain it is AETS (Agencia de Evaluación de Tecnologías Sanitarias) that is responsible for HTA evaluations. Once HTA has evaluated test’s clinical effectiveness and cost-effectiveness, the results of HTA assesment are typically presented to health policy makers, who use this information to make decisions regarding the adoption, funding, and regulation of the test in healthcare systems.
Figure 2. Description of key steps and stakeholders involved in analytical and clinical validity, clinical and economic utility.
Another important stakeholder to bring early in this process are key opinion leaders, clinicians who can support manufacturer in many ways such as evidence generation, impact studies, contribute to shaping European guidelines, a key step prior to reimbursement of molecular diagnostics in Europe. Ideally, the inclusion of novel approach into International and National guidelines, should precede or occur at the same time as the presentation of HTA results to policy makers. On that matter, inclusion / recommendation of a novel method into European clinical guidelines is way more difficult than what is observed in US for instance with NCCN Guidelines – in Europe, you would typically need to have a clinical utility study led by ideally a group of pan-European clinicians, who would then publish a peer-review publication presenting the positive findings using this novel approach. In instances where there is doubt around clinical utility demonstration, KOLs together with manufacturers staff (typically lead by manufacturer’s Governmental Affairs and Market Access teams) would meet with ministry of health to design implementation studies. HTA evaluations are one path to coverage used in some countries, whereas in others the focus is set on implementation studies, national programs and legislation, such as UK’s NHS Genomic Medicine Service progam and Plan Cancer 2014-2019 in France, which have positively influenced reimbursement landscapes in respective countries.
Varied reimbursement pathways across EU require manufacturers of novel diagnostic tools to generate robust clinical evidence, conduct thorough economic analyses, and actively engage with stakeholders early one, in order to successfully navigate this complexity. Understanding these nuances and having a thorough European Reimbursement Roadmap which includes evidence generating and KOL engagement strategy, as well as initiating early dialogue with local HTA bodies / payers are crucial steps for manufacturers who aim to secure favourable reimbursement and ensure patient access to innovative diagnostic solutions.
- Soria JC, Ohe Y, Vansteenkiste J, et al. Osimertinib in Untreated EGFR-Mutated Advanced Non-Small-Cell Lung Cancer. N Engl J Med. Jan 11 2018;378(2):113-125. doi:10.1056/NEJMoa1713137
- Chazan G, Franchini F, Shah R, et al. Real-World Treatment and Outcomes in ALK-Rearranged NSCLC: Results From a Large U.S.-Based Database. JTO Clin Res Rep. Aug 2024;5(8):100662. doi:10.1016/j.jtocrr.2024.100662
- Horgan D, Hofman P, Giacomini P, et al. Challenges and barriers for the adoption of personalized medicine in Europe: the case of Oncotype DX Breast Recurrence Score(®) test. Diagnosis (Berl). Dec 17 2024;doi:10.1515/dx-2024-0127
