Constructive technology assessment of gene expression profiling for breast cancer

Constructive Technology Assessment (CTA) can be used as a complementary\ud approach to Health Technology Assessment (HTA), especially for the early and\ud dynamic introduction of new technologies in a controlled way. CTA is based on the\ud idea that during the course of technology development, choices are constantly\ud being made about the form, the function, and the use of that technology. In this\ud dissertation the mixed method approach of CTA covers an integral assessment of\ud clinical, economic, patient-related, ethical/juridical, and organizational domains.\ud Diffusion scenarios, which are commonly applied in industry to anticipate on their\ud strategies concerning future development, have been adapted to monitor the\ud dynamics in this study.\ud The aim of this dissertation was to contribute to the knowledge on early stage HTA\ud by performing a CTA for the introduction and diffusion of gene expression profiling\ud for breast cancer patients. As a clinical case, the introduction and diffusion of the\ud 70-gene prognosis signature (MammaPrintTM) using microarray analysis was\ud evaluated. The research objectives were twofold: first to develop the CTA method\ud in early stages of technology development and second, to apply the CTA method\ud to the case of the 70-gene signature for breast cancer, in order to support and\ud anticipate on the introduction of this new diagnostic test, specified in different CTA\ud aspects.\ud This study showed that the CTA methodology can be a useful tool to guide\ud controlled early implementation of a promising technology and its possible use for\ud coverage decisions, in this case the 70-gene signature for breast cancer patients.\ud The patient information regarding the 70-gene signature appeared to be clear and\ud satisfactory and resulted in a good understanding of (the consequences of) the\ud genomic profile. In general, the 70-gene signature seems most cost-effective in\ud terms of quality adjusted life years; the slightly more sensitive tests deliver more life\ud years, but leads to a substantial larger amount of adjuvant chemotherapy and\ud hence higher costs, thus demanding a higher willingness to pay. Developing the\ud 70-gene signature based on paraffin instead of fresh frozen tissue could establish\ud a higher cost-effectiveness and could thus be a worthwhile investment. Finally,\ud when incorporating scenarios in the decision model, it became apparent that early\ud anticipation on certain aspects is necessary to reach the potential costeffectiveness

MammaPrint is cost-effective compared to clinical risk assessment in early stage breast cancer

Rationale: The 70-gene signature (MammaPrint®, MP) is a prognostic test which guides treatment decisions in patients with early breast cancer. After level 1A evidence for clinical utility of MP has been proven, cost-effectiveness data is important to inform reimbursement. Research objectives: To compare cost-effectiveness of adding MP to clinical risk assessment versus clinical risk assessment alone for the US and EU. Clinical risk was assessed by Adjuvant Online! (AOL) as described in Cardoso et al. NEJM 2016. We used prospective survival data from the large randomized phase 3 trial 'Microarray In Node-negative and 1 to 3 positive lymph node Disease may Avoid ChemoTherapy' (MINDACT). Methods: We used a Markov decision model to estimate the expected costs and outcomes (quality adjusted life years; QALYs) for MP versus AOL in early breast cancer patients from a payers perspective in the US and a societal perspective in the EU over a 5 year time horizon. Five year breast cancer overall- and distant metastasis free survival was calculated based on the MINDACT population (n=6,693). Utility scores were collected by means of the EuroQol-5D in the pilot phase of MINDACT(the first n=800 MINDACT patients). Cost data were for the US based on published insurance claim data, for the EU on published health care- and societal costs. The cost-effectiveness was calculated for: (1) total early stage breast cancer population, (2) clinical high risk population and (3) clinical high risk group in the ER+/HER2- population. Finally, budget impact for a high-low range of different countries was calculated, as the application and costs of chemotherapy can be highly variable between countries. Results: For all groups (1,2,and 3) in the US, using MINDACT survival data and insurance claim data, adding MP to AOL saved costs and gained more QALYs compared to AOL alone (total costs per patient $42,223 vs$45,566 and 4.035 vs 4.031 QALYs respectively). Thus, a small difference in quality adjusted life years (0,0041) was observed, whereas a large difference in costs (3,342) renders MP a highly cost-effective test (less costly & more effective in 64% of the cases). The largest cost-benefit effect was seen for group 3. The cut-off point for MP being cost-effective in the total population (group 1) is when the chemotherapy costs (and consequences) together are above 30,000. In the US, with approximately 250,000 new breast cancer patients per year, and a cost saving of $3,342, annual budget savings are expected to be$836M. Similar results for the Netherlands (15,000 breast cancer patients per year), reveal a cost difference of $300 per patient, and overall annual budget savings are expected to be$4,5M. Conclusion: Adding MP to clinical risk assessment is highly cost-effective compared to clinical risk assessment alone, based on the MINDACT survival data and US insurance claim data, for all above mentioned groups. When costs for chemotherapy (and consequences) exceed $30,000, MP is cost-effective for the total early breast cancer population. When costs for chemotherapy (and consequences) are below$30,000, the MP is cost-effective for the clinical high risk early breast cancer group. The separate results for EU countries will follow