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

Establishing cost-effectiveness of genetic targeting of cancer therapies

The clinical benefit of a new genomic instrument, the 70-gene signature for breast cancer patients, is being evaluated in a randomised clinical trial. The early, controlled implementation process is supported by a Constructive Technology Assessment to help decision-making in an uncertain time of development

Establishing cost-effectiveness of genetic targeting of cancer therapies\ud

The clinical benefit of a new genomic instrument, the 70-gene signature\ud for breast cancer patients, is being evaluated in a randomised clinical\ud trial. The early, controlled implementation process is supported by a\ud Constructive Technology Assessment to help decision-making in an\ud uncertain time of developmen

Differences in time to patient access to innovative cancer medicines in six European countries

Patients across Europe face inequity regarding access to anticancer medicines. While access is typically evaluated through reimbursement status or sales data, patients can receive first access through early access programs (EAPs) or off-label use. This study aims to assess the time to patient access at the hospital level, considering different indications and countries. (Pre-)registered access to six innovative medicines (Olaparib, Niraparib, Ipilimumab, Osimeritinib, Nivolumab and Ibritunib) was measured using a cross-sectional survey. First patient access to medicines and indications were collected using the hospital databases. Nineteen hospitals from Hungary, Italy, the Netherlands, Belgium, Switzerland and France participated. Analysis showed that some hospitals achieved patient access before national reimbursement, primarily through EAPs. The average time from EMA-approval to patient access for these medicines was 2.1 years (Range: −0.9-7.1 years). Hospitals in Italy and France had faster access compared to Hungary and Belgium. Variation was also found within countries, with specialized hospitals (x̄: −0.9 years; SD: 2.0) more likely to provide patient access prior to national reimbursement than general hospitals (x̄: 0.4 years; SD: 2.9). Contextual differences were observed, with EAPs or off-label use being more prevalent in Switzerland than Hungary. Recent EMA-approved indications and drug combinations reached patients at a later stage. Substantial variation in patient access time was observed between and within countries. Improving pricing and reimbursement timelines, fostering collaboration between national health authorities and market authorization holders, and implementing nationally harmonized, data-generating EAPs can enhance timely and equitable patient access to innovative cancer treatments in Europe.</p

Dynamic Simulation Modeling to Analyze the Impact of Whole Genome Sequencing National Implementation Scenarios in Lung cancer on Time-to-Treatment, Costs and Patient Demand

Background Although Whole Genome Sequencing (WGS) is increasingly proposed to unravel molecular origins of advanced cancers, it is less clear if and how WGS should be routinely offered in the health service. The objective of this study is to investigate how the cost per patient and time-to-treatment is affected if WGS were implemented in the national health system and how these outcomes differ among subgroups of patients with lung cancer. This first-ever study used health systems simulation modeling to analyze implementation scenarios ensuring sustainable access to cancer treatment.Methods A base case and three scenarios (varying stage of disease and hospitals offering WGS) the optimal placement of WGS in the diagnostic pathway was simulated using a dynamic simulation model. The model simulated lung cancer patients undergoing molecular diagnostic procedures in one or multiple hospitals. The model also included patient and healthcare provider heterogeneity as well as referral patterns of lung cancer (LC) patients using patient-level data obtained from the Netherlands Cancer Registry. Model outcomes were the time-to-treatment, total diagnostic cost, and the demand for WGS sequencing capacity including the expertise of a molecular tumor board.Results The time-to-treatment ranged between 20-46 days for all four scenarios considered. The cost of molecular diagnostic testing per patient ranged from €621 in the base case to €1930 in the scenario where all LC patients (stage I-IV) receive upfront WGS. Compared to the base case, upfront testing using WGS in all LC patients led to a 33% reduction in the time-to-treatment, a 210% increase in the cost per patient and a six-fold increase in total diagnostic costs.Conclusions This first-ever study investigating implementation scenario’s demonstrated that upfront WGS for all lung cancer patients can reduce the time to treatment yet at a higher cost. However, upfront WGS also reduces diagnostic pathway complexity, which may improve care planning and treatment efficiency. The model is versatile in its approach to study the impact of price discounts or the amount of actionable targets tested for and further analysis showed discounts on consumables up to 50% imply WGS would the preferred strategy

Duty to recontact in genomic cancer care:A tool helping to assess the professional's responsibility

Tumour DNA and germline testing, based on DNA-wide sequencing analysis, are becoming more and more routine in clinical-oncology practice. A promising step in medicine, but at the same time leading to challenging ethicolegal questions. An important one is under what conditions individuals (patients and their relatives, research participants) should be recontacted with new information, even if many years have passed since the last contact. Based on legal- and ethical study, we developed a tool to help professionals to decide whether or not to recontact an individual in specific cases. It is based on four assessment criteria: (1) professional relationship (2) clinical impact (3) individual's preferences and (4) feasibility. The tool could also serve as a framework for guidelines on the topic.</p

Supporting participation in paid work of cancer survivors and their partners in the Netherlands:protocol of the SusTained Employability in cancer Patients and their partnerS (STEPS) multi-centre randomized controlled trial and cohort study

BACKGROUND: Many cancer survivors experience physical and/or psychosocial problems affecting return to work (RTW) and work retention. Current interventions on RTW lack evidence regarding effectiveness, while interventions for work retention are missing. Partners of cancer survivors may also experience work- and health-related outcomes; yet, these consequences are not well understood. Here, the protocol of the STEPS study is described. The study aims are to: 1) evaluate the (cost-)effectiveness of a rehabilitation program for RTW and work retention in cancer survivors, and 2) assess health- and work-related outcomes among cancer survivors' partners. METHODS: In a multicentre Randomized Controlled Trial (RCT), 236 working-age cancer survivors with an employment contract will be randomly allocated to a usual care group or an intervention group receiving a multidisciplinary rehabilitation program, combining occupational therapy facilitating work retention (e.g., energy management and self-efficacy training) and reintegration consultation addressing work-related issues (e.g., RTW planning and discussing workplace or task modifications with the supervisor). Alongside the RCT, a prospective cohort study will be conducted among cancer survivors' partners (n = 267). Participants in the RCT and cohort study will be asked to complete questionnaires at baseline, and after six and 12 months, assessing work- and health-related outcomes. Generalized estimating equations will be used to assess intervention's effectiveness, compared to usual care, regarding primary (i.e., working hours per week) and secondary outcomes. Also economic and process evaluations will be performed. For the cohort study, logistic or linear regression modelling will be applied assessing work- and health-related outcomes (primary outcome: working hours) of cancer survivors' partners, and what factors predict these outcomes. RESULTS: The study is planned to start in September 2021; results are expected in 2023. CONCLUSION: Compared to usual care, the STEPS intervention is hypothesized to be (cost-)effective and the intervention could be a valuable addition to standard care helping cancer survivors to sustain employment. Further, it is expected that living with a cancer survivor has a substantial impact on work and health of partners, while specific groups of partners that are at particular risk for this impact are likely to be identified. TRIAL REGISTRATION: Dutch Trial Register ( NTR;NL9094 ; 15-12-2020)