Valesca P. Retèl

Cost-effectiveness of the 70-gene signature versus St. Gallen guidelines and Adjuvant Online for early breast cancer

BACKGROUND The 70-gene signature (MammaPrint) is a prognostic test used to guide adjuvant treatment decisions in patients with node-negative breast cancer. In order to decide upon its use, a systematic comparative analysis of the effects of the 70-gene signature, the Sankt Gallen guidelines and the Adjuvant Online Software for these patients on survival, quality of life and costs is warranted. METHODS A Markov decision model was used to simulate the 20-year costs and outcomes (survival and quality-of-life adjusted survival (QALYs)) in a hypothetical cohort of node-negative, estrogen receptor positive breast cancer patients. Sensitivity and specificity of the three prognostic tools were based on 5 and 10 years breast cancer specific survival and distant metastasis as first event, derived from a pooled analysis consisting of 305 tumour samples from 3 previously reported validation studies concerning the 70-gene signature. RESULTS Small differences in survival, but substantial differences in quality-adjusted survival between the prognostic tools were observed. Quality-adjusted survival was highest when using the 70-gene signature. Based on costs per QALY, the 70-gene has the highest probability of being cost-effective for a willingness to pay for a QALY higher than euro12.000. Sankt Gallen showed the highest survival rates compared to the 70-gene signature, but leads to a substantial larger amount of adjuvant chemotherapy and lower cost-effectiveness, thus demanding a high willingness to pay to save a life year. CONCLUSIONS When deciding upon the cost-effectiveness of the prognostic tests, the 70-gene signature improves quality-adjusted survival and has the highest probability of being cost-effective.

A cost-effectiveness analysis of a preventive exercise program for patients with advanced head and neck cancer treated with concomitant chemo-radiotherapy

BackgroundConcomitant chemo-radiotherapy (CCRT) has become an indispensable organ, but not always function preserving treatment modality for advanced head and neck cancer. To prevent/limit the functional side effects of CCRT, special exercise programs are increasingly explored. This study presents cost-effectiveness analyses of a preventive (swallowing) exercise program (PREP) compared to usual care (UC) from a health care perspective.MethodsA Markov decision model of PREP versus UC was developed for CCRT in advanced head and neck cancer. Main outcome variables were tube dependency at one-year and number of post-CCRT hospital admission days. Primary outcome was costs per quality adjusted life years (cost/QALY), with an incremental cost-effectiveness ratio (ICER) as outcome parameter. The Expected Value of Perfect Information (EVPI) was calculated to obtain the value of further research.ResultsPREP resulted in less tube dependency (3% and 25%, respectively), and in fewer hospital admission days than UC (3.2 and 4.5 days respectively). Total costs for UC amounted to €41,986 and for PREP to €42,271. Quality adjusted life years for UC amounted to 0.68 and for PREP to 0.77. Based on costs per QALY, PREP has a higher probability of being cost-effective as long as the willingness to pay threshold for 1 additional QALY is at least €3,200/QALY. At the prevailing threshold of €20,000/QALY the probability for PREP being cost-effective compared to UC was 83%. The EVPI demonstrated potential value in undertaking additional research to reduce the existing decision uncertainty.ConclusionsBased on current evidence, PREP for CCRT in advanced head and neck cancer has the higher probability of being cost-effective when compared to UC. Moreover, the majority of sensitivity analyses produced ICERs that are well below the prevailing willingness to pay threshold for an additional QALY (range from dominance till €45,906/QALY).

Review on early technology assessments of nanotechnologies in oncology

Nanotechnology is expected to play an increasingly important role in the diagnostics, prognostics, and management of targeted cancer treatments. While papers have described promising results for nanotechnology in experimental settings, the translation of fundamental research into clinical applications has yet to be widely adopted. In future, policy makers will need to anticipate new developments for clinical implementation and introduce technology assessments. Here we present an overview of the literature on the technology assessments that have already been undertaken on early stage nanotechnology in cancer care, with particular emphasis placed on clinical efficacy, efficiency, logistics, patient‐related features and technology dynamics.

Prospective cost-effectiveness analysis of genomic profiling in breast cancer

BACKGROUND The cost-effectiveness of the 70-gene signature (70-GS) (MammaPrint®) has earlier been estimated using retrospective validation data. Based on the prospective 5-year survival data of the microarRAy-prognoSTics-in-breast-cancER (RASTER) study, the aim here was to evaluate the cost-effectiveness reflecting the actual use in clinical practice, including reality-based compliance rates. METHODS Costs and outcomes (quality-adjusted-life-years (QALYs)) were calculated in node-negative (N-) patients included in the RASTER study (n=427). Sensitivity and specificity of the 70-gene and Adjuvant! Online (AO) were based on 5-year distant-disease-free survival (DDFS). Subgroup analyses were performed for two groups for whom benefit of the 70-gene had earlier been reported: (1) ductal, oestrogen receptor-positive (ER+), tumour diameter 10-30 mm, grade II, age 40-70; (2) ductal, oestrogen receptor-positive, tumour diameter 5-30 mm, grade II/III and age 40-70. RESULTS Based on 5-year survival data, the cost-effectiveness of the 70-gene signature versus AO was prospectively confirmed. The total health care costs per patient were €26,786 for the 70-gene and €29,187 for AO. The quality adjusted life years yielded 12.49 and 11.88, respectively. The subgroups retrieved slightly higher life gains and higher costs, but all resulted finally in a favourable position for the 70-gene signature. CONCLUSIONS The use of the 70-gene signature, as judged appropriate by doctors and patients and supported by a low risk 70-gene signature as an oncological safe choice, was also found to be cost-effective.

Scenario drafting to anticipate future developments in technology assessment

BackgroundHealth Technology Assessment (HTA) information, and in particular cost-effectiveness data is needed to guide decisions, preferably already in early stages of technological development. However, at that moment there is usually a high degree of uncertainty, because evidence is limited and different development paths are still possible. We developed a multi-parameter framework to assess dynamic aspects of a technology -still in development-, by means of scenario drafting to determine the effects, costs and cost-effectiveness of possible future diffusion patterns. Secondly, we explored the value of this method on the case of the clinical implementation of the 70-gene signature for breast cancer, a gene expression profile for selecting patients who will benefit most from chemotherapy.MethodsTo incorporate process-uncertainty, ten possible scenarios regarding the introduction of the 70-gene signature were drafted with European experts. Out of 5 most likely scenarios, 3 drivers of diffusion (non-compliance, technical failure, and uptake) were quantitatively integrated in a decision-analytical model. For these scenarios, the cost-effectiveness of the 70-gene signature expressed in Incremental Cost-Effectiveness Ratios (ICERs) was compared to clinical guidelines, calculated from the past (2005) until the future (2020).ResultsIn 2005 the ICER was €1,9 million/quality-adjusted-life-year (QALY), meaning that the 70-gene signature was not yet cost-effective compared to the current clinical guideline. The ICER for the 70-gene signature improved over time with a range of €1,9 million to €26,145 in 2010 and €1,9 million to €11,123/QALY in 2020 depending on the separate scenario used. From 2010, the 70-gene signature should be cost-effective, based on the combined scenario. The uptake-scenario had strongest influence on the cost-effectiveness.ConclusionsWhen optimal diffusion of a technology is sought, incorporating process-uncertainty by means of scenario drafting into a decision model may reveal unanticipated developments and can demonstrate a range of possible cost-effectiveness outcomes. The effect of scenarios give additional information on the speed with cost effectiveness might be reached and thus provide a more realistic picture for policy makers, opinion leaders and manufacturers.

Next-generation sequencing in NSCLC and melanoma patients: a cost and budget impact analysis

Next-generation sequencing (NGS) has reached the molecular diagnostic laboratories. Although the NGS technology aims to improve the effectiveness of therapies by selecting the most promising therapy, concerns are that NGS testing is expensive and that the ‘benefits’ are not yet in relation to these costs. In this study, we give an estimation of the costs and an institutional and national budget impact of various types of NGS tests in non-small-cell lung cancer (NSCLC) and melanoma patients within The Netherlands. First, an activity-based costing (ABC) analysis has been conducted on the costs of two examples of NGS panels (small- and medium-targeted gene panel (TGP)) based on data of The Netherlands Cancer Institute (NKI). Second, we performed a budget impact analysis (BIA) to estimate the current (2015) and future (2020) budget impact of NGS on molecular diagnostics for NSCLC and melanoma patients in The Netherlands. Literature, expert opinions, and a data set of patients within the NKI (n = 172) have been included in the BIA. Based on our analysis, we expect that the NGS test cost concerns will be limited. In the current situation, NGS can indeed result in higher diagnostic test costs, which is mainly related to required additional tests besides the small TGP. However, in the future, we expect that the use of whole-genome sequencing (WGS) will increase, for which it is expected that additional tests can be (partly) avoided. Although the current clinical benefits are expected to be limited, the research potentials of NGS are already an important advantage.

Early stage cost-effectiveness analysis of a BRCA1-like test to detect triple negative breast cancers responsive to high dose alkylating chemotherapy.

PURPOSE Triple negative breast cancers (TNBC) with a BRCA1-like profile may benefit from high dose alkylating chemotherapy (HDAC). This study examines whether BRCA1-like testing to target effective HDAC in TNBC patients can be more cost-effective than treating all patients with standard chemotherapy. Additionally, we estimated the minimum required prevalence of BRCA1-like and the required positive predictive value (PPV) for a BRCA1-like test to become cost-effective. METHODS Our Markov model compared 1) the incremental costs; 2) the incremental number of respondents; 3) the incremental number of Quality Adjusted Life Years (QALYs); and 4) the incremental cost-effectiveness ratio (ICER) of treating TNBC women with personalized HDAC based on BRCA1-like testing vs. standard chemotherapy, from a Dutch societal perspective and a 20-year time horizon, using probabilistic sensitivity analysis. Furthermore, we performed one-way sensitivity analysis (SA) to all model parameters, and two-way SA to prevalence and PPV. Data were obtained from a current trial (NCT01057069), published literature and expert opinions. RESULTS BRCA1-like testing to target effective HDAC would presently not be cost-effective at a willingness-to-pay threshold of €80.000/QALY (€81.981/QALY). SAs show that PPV drives the ICER changes. Lower bounds for the prevalence and the PPV were found to be 58.5% and 73.0% respectively. CONCLUSION BRCA1-like testing to target effective HDAC treatment in TNBC patients is currently not cost-effective at a willingness-to-pay of €80.000/QALY, but it can be when a minimum PPV of 73% is obtained in clinical practice. This information can help test developers and clinicians in decisions on further research and development of BRCA1-like tests.

Scenario drafting for early technology assessment of next generation sequencing in clinical oncology

BackgroundNext Generation Sequencing (NGS) is expected to lift molecular diagnostics in clinical oncology to the next level. It enables simultaneous identification of mutations in a patient tumor, after which targeted therapy may be assigned. This approach could improve patient survival and/or assist in controlling healthcare costs by offering expensive treatment to only those likely to benefit. However, NGS has yet to make its way into the clinic. Health Technology Assessment can support the adoption and implementation of a novel technology, but at this early stage many of the required variables are still unknown.MethodsScenario drafting and expert elicitation via a questionnaire were used to identify factors that may act as a barrier or facilitate adoption of NGS-based molecular diagnostics. Attention was paid to predominantly elicit quantitative answers, allowing their use in future modelling of cost-effectiveness.ResultsAdequately informing patients and physicians, the latters’ opinion on clinical utility and underlying evidence as well as presenting sequencing results within a relevant timeframe may act as pivotal facilitators. Reimbursement for NGS-based testing and accompanying therapies (both general and in case of off-label prescription) was found to be a potential barrier. Competition on the market and demonstrating clinical utility may also be challenging. Importantly, numerous quantitative values for variables related to each of these potential barriers/facilitators, such as such as desired panel characteristics, willingness to pay or the expected number of targets identified per person, were also elicited.ConclusionsWe have identified several factors that may either pose a barrier or facilitate the adoption of NGS in the clinic. We believe acting upon these findings, for instance by organizing educational events, advocating new ways of evidence generation and steering towards the most cost-effective solution, will accelerate the route from bench-to-bedside. Moreover, due to the methodology of expert elicitation, this study provides parameters that can be incorporated in future cost-effectiveness modeling to steer the development of NGS gene panels towards the most optimal direction.

Cost-Effectiveness of 18f-Fdg Pet/Ct for Screening Distant Metastasis in Stage Ii/Iii Breast Cancer Patients of the UK, the United States and the Netherlands

Objectives: 18F-FDG-PET/CT is accurate in detecting distant metastases (DM) in breast cancer patients scheduled for neoadjuvant chemotherapy. If DMs are screen-detected in an early phase, morbidity and mortality may be reduced. Because 18F-FDG-PET/CT comes at a significant cost, we compared its expected cost-effectiveness in stage II/III breast cancer patients of the UK, the US and the Netherlands (NL) vs. the gold-standard (X-thorax/liver sonography/bone scan (UK/NL) and CT-thorax-abdomen/bone scan (US)). Methods: A time-dependent Markov model compared expected Life Year (LY) and cost/Quality-adjusted Life Year (QALY) gained in four breast cancer subtypes (ER-/HER2+;ER+/HER2+;ER-/HER2-;ER+/HER2-) over a 5-year time horizon from a hospital perspective. Sensitivity and specificity of imaging and type of systemic and local treatments were derived from the Netherlands Cancer Institute. Epidemiological, survival and utility data were estimated from literature or informed by expert assumptions. Costs (2013) were derived from national tariffs (UK and NL), and from the Centres for Medicaid and Medicare Services (US). Results: 18F-FDG-PET/CT is more sensitive (53% vs. 15%) and specific (97% vs. 94%) than the gold-standard. LYs and QALYs gained were similar across subtypes, ranging from 0.025 to 0.027 and 0.0037 to 0.0044 respectively. In all countries, ER+HER2+ was the least and ER+HER2- the most costly group. 18F-FDG-PET/CT is expected to be cost-effective in the NL and the US (with highest ICERs of €165/QALY in ER+/HER2+ and

Molecular Profiling Is Rather Likely to Be Cost Effective

750 in ER-HER2+), with probabilities of cost-effectiveness ranging from 46-52% and 62-72% respectively, but not in the UK, with a 66-75% probability, depending on tumor subtype. Conclusions: Using 18F-FDG-PET/CT for DM screening in stage II/III breast cancer is expected to result in incremental QALY gains in all subtypes and countries. Due to costs differences between countries, 18F-FDG-PET/CT is expected to be cost-effective in the US and the NL, but not in the UK.