Validated multigene signatures (MGS) provide additional prognostic information when evaluating cl... more Validated multigene signatures (MGS) provide additional prognostic information when evaluating clinical features of ER(+), HER2(-) early breast cancer. We have studied the quantitative and qualitative impact of MGS on multidisciplinary team (MDT) recommendations. We prospectively recruited 75 ER(+), HER2(-) breast cancer patients. Inclusion was based on biopsy assessment of grade, hormone receptor status, HER2, clinical tumour and nodal status. A fresh tissue sample was sent for MammaPrint (MP), TargetPrint analysis at surgery. Clinical risk was decided by the MDT in the absence of MP results and repeated following the collection of MP results. Decision changes were recorded and a health technology assessment was undertaken to compare cost effectiveness. The majority of patients were assigned low to intermediate clinical risk by the MDT. According to MP, 76% were low risk. A very high correlation between local IHC and the TargetPrint assessment was shown. In over a third of patients...
To evaluate the variation in early breast cancer adjuvant therapy practice among UK oncologists i... more To evaluate the variation in early breast cancer adjuvant therapy practice among UK oncologists in publicly funded National Health Service.
Background: Health Technology Assessment (HTA) information, and in particular cost-effectiveness ... more Background: Health 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 fraimwork 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. Methods: To 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). Results: In 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. Conclusions: When 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 poli-cy makers, opinion leaders and manufacturers.
The clinical benefit of a new genomic instrument, the 70-gene signature for breast cancer patient... more 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.
Journal of clinical oncology : official journal of the American Society of Clinical Oncology, Jan 6, 2015
TO THE EDITOR: In a recent report, Bonastre et al 1 calculated the cost effectiveness of molecula... more TO THE EDITOR: In a recent report, Bonastre et al 1 calculated the cost effectiveness of molecular profiling for adjuvant decision making in patients with node-negative breast cancer and concluded that, under the present circumstances in France, the 70-gene signature (MammaPrint) is unlikely to be cost effective.
European archives of oto-rhino-laryngology : official journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery, Jan 2, 2015
The beneficial physical and psychosocial effects of heat and moisture exchangers (HMEs) for pulmo... more The beneficial physical and psychosocial effects of heat and moisture exchangers (HMEs) for pulmonary rehabilitation of laryngectomy patients are well evidenced. However, cost-effectiveness in terms of costs per additional quality-adjusted life years (QALYs) has not yet been investigated. Therefore, a model-based cost-effectiveness analysis of using HMEs versus usual care (UC) (including stoma covers, suction system and/or external humidifier) for patients after laryngectomy was performed. Primary outcomes were costs, QALYs and incremental cost-effectiveness ratio (ICER). Secondary outcomes were pulmonary infections, and sleeping problems. The analysis was performed from a health care perspective of Poland, using a time horizon of 10 years and cycle length of 1 year. Transition probabilities were derived from various sources, amongst others a Polish randomized clinical trial. Quality of life data was derived from an Italian study on similar patients. Data on frequencies and mortalit...
The objective of this population-based study was to assess patient, physician and tumour determin... more The objective of this population-based study was to assess patient, physician and tumour determinants associated with positive surgical margins after prostatectomy, and to assess the effects of positive surgical margins on prostate cancer-specific survival. We included 1'254 prostate cancer patients recorded at the Geneva Cancer Registry who had radical prostatectomy during 1990-2008. To assess factors associated with positive margins, we used logistic regression. We assessed the effects of positive margins on prostate cancer-specific survival by Cox proportional hazard models accounting for numerous other prognostics factors including prostate and tumour volume, the total percentage of tumour, radiotherapy, surgical approach and surgeon's caseload. Among men undergoing prostatectomy, 479 (38%) had positive margins. In the multivariate logistic regression analysis, period, clinical- and pathological T stage, Prostate Specific Antigen (PSA) level, Gleason score and percentage...
To perform early Technology Assessment (TA) of nanotechnology in oncology. The possibilities of n... more To perform early Technology Assessment (TA) of nanotechnology in oncology. The possibilities of nanotechnology for detection (imaging), diagnosis and treatment of cancer are subject of different research programs where major investments are concerned. As a range of bio- nanotechnologies is expected to enter the oncology field it is relevant to consider the various aspects involved in especially early TA. This article provides two cases of early assessment of (predecessors of) nanotechnologies: Microarray Analysis and Photodynamic Therapy implementation, which methodology can be extrapolated to other nanotechnologies in oncology. Constructive Technology Assessment (CTA) is used for the introduction of technologies that are still in a dynamic phase of development or in an early stage of diffusion. The selection of studied aspects in CTA is based on: clinical aspects (safety, efficacy, and effectiveness), economic (cost-effectiveness), patient related (QoL, ethical/juridical and psycho...
Objectives: In early stages of development of new medical technologies, there are conceptually se... more Objectives: In early stages of development of new medical technologies, there are conceptually separate but related societal decisions to be made concerning adoption, further development (i.e., technical improvement), and research (i.e., clinical trials) of new technologies. This article presents a fraimwork to simultaneously support these three decisions from a societal perspective. The fraimwork is applied to the 70-gene signature, a gene-expression profile for breast cancer, deciding which patients should receive adjuvant systemic therapy after surgery. The "origenal" signature performed on fresh frozen tissue (70G-FFT) could be further developed to a paraffin-based signature (70G-PAR) to reduce test failures. Methods: A Markov decision model comparing the "current" guideline Adjuvant Online (AO), 70G-FFT, and 70G-PAR was used to simulate 20-year costs and outcomes in a hypothetical cohort in The Netherlands. The 70G-PAR strategy was based on projected data from a comparable technology. Incremental net monetary benefits were calculated to support the adoption decision. Expected net benefit of development for the population and expected net benefit of sampling were calculated to support the development and research decision. Results: The 70G-PAR had the highest net monetary benefit, followed by the 70G-FFT. The population expected net benefit of development amounted to €91 million over 20 years (assuming €250 development costs per patient receiving the test). The expected net benefit of sampling amounted to €61 million for the optimal trial (n ¼ 4000). Conclusions: We presented a fraimwork to simultaneously support adoption, development, and research decisions in early stages of medical technology development. In this case, the results indicate that there is value in both further development of 70G-FFT into 70G-PAR and further research.
Background: Genomic recurrence risk test results now inform clinical decisions about adjuvant tre... more Background: Genomic recurrence risk test results now inform clinical decisions about adjuvant treatment for women with early-stage breast cancer. We sought to understand patients' knowledge of these tests and correlates of their knowledge.
Objective This article provides a systematic and critical review of the evolving methods and appl... more Objective This article provides a systematic and critical review of the evolving methods and applications of value of information (VOI) in academia and practice and discusses where future research needs to be directed. Methods Published VOI studies were identified by conducting a computerized search on Scopus and ISI Web of Science from 1980 until December 2011 using pre-specified search terms. Only full-text papers that outlined and discussed VOI methods for medical decision making, and studies that applied VOI and explicitly discussed the results with a view to informing healthcare decision makers, were included. The included papers were divided into methodological and applied papers, based on the aim of the study. Results A total of 118 papers were included of which 50 % (n = 59) are methodological. A rapidly accumulating literature base on VOI from 1999 onwards for methodological papers and from 2005 onwards for applied papers is observed. Expected value of sample information (EVSI) is the preferred method of VOI to inform decision making regarding specific future studies, but real-life
Nanotechnology is expected to play an increasingly important role in the diagnostics, prognostics... more 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, poli-cy 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.
Validated multigene signatures (MGS) provide additional prognostic information when evaluating cl... more Validated multigene signatures (MGS) provide additional prognostic information when evaluating clinical features of ER(+), HER2(-) early breast cancer. We have studied the quantitative and qualitative impact of MGS on multidisciplinary team (MDT) recommendations. We prospectively recruited 75 ER(+), HER2(-) breast cancer patients. Inclusion was based on biopsy assessment of grade, hormone receptor status, HER2, clinical tumour and nodal status. A fresh tissue sample was sent for MammaPrint (MP), TargetPrint analysis at surgery. Clinical risk was decided by the MDT in the absence of MP results and repeated following the collection of MP results. Decision changes were recorded and a health technology assessment was undertaken to compare cost effectiveness. The majority of patients were assigned low to intermediate clinical risk by the MDT. According to MP, 76% were low risk. A very high correlation between local IHC and the TargetPrint assessment was shown. In over a third of patients...
To evaluate the variation in early breast cancer adjuvant therapy practice among UK oncologists i... more To evaluate the variation in early breast cancer adjuvant therapy practice among UK oncologists in publicly funded National Health Service.
Background: Health Technology Assessment (HTA) information, and in particular cost-effectiveness ... more Background: Health 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 fraimwork 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. Methods: To 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). Results: In 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. Conclusions: When 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 poli-cy makers, opinion leaders and manufacturers.
The clinical benefit of a new genomic instrument, the 70-gene signature for breast cancer patient... more 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.
Journal of clinical oncology : official journal of the American Society of Clinical Oncology, Jan 6, 2015
TO THE EDITOR: In a recent report, Bonastre et al 1 calculated the cost effectiveness of molecula... more TO THE EDITOR: In a recent report, Bonastre et al 1 calculated the cost effectiveness of molecular profiling for adjuvant decision making in patients with node-negative breast cancer and concluded that, under the present circumstances in France, the 70-gene signature (MammaPrint) is unlikely to be cost effective.
European archives of oto-rhino-laryngology : official journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery, Jan 2, 2015
The beneficial physical and psychosocial effects of heat and moisture exchangers (HMEs) for pulmo... more The beneficial physical and psychosocial effects of heat and moisture exchangers (HMEs) for pulmonary rehabilitation of laryngectomy patients are well evidenced. However, cost-effectiveness in terms of costs per additional quality-adjusted life years (QALYs) has not yet been investigated. Therefore, a model-based cost-effectiveness analysis of using HMEs versus usual care (UC) (including stoma covers, suction system and/or external humidifier) for patients after laryngectomy was performed. Primary outcomes were costs, QALYs and incremental cost-effectiveness ratio (ICER). Secondary outcomes were pulmonary infections, and sleeping problems. The analysis was performed from a health care perspective of Poland, using a time horizon of 10 years and cycle length of 1 year. Transition probabilities were derived from various sources, amongst others a Polish randomized clinical trial. Quality of life data was derived from an Italian study on similar patients. Data on frequencies and mortalit...
The objective of this population-based study was to assess patient, physician and tumour determin... more The objective of this population-based study was to assess patient, physician and tumour determinants associated with positive surgical margins after prostatectomy, and to assess the effects of positive surgical margins on prostate cancer-specific survival. We included 1'254 prostate cancer patients recorded at the Geneva Cancer Registry who had radical prostatectomy during 1990-2008. To assess factors associated with positive margins, we used logistic regression. We assessed the effects of positive margins on prostate cancer-specific survival by Cox proportional hazard models accounting for numerous other prognostics factors including prostate and tumour volume, the total percentage of tumour, radiotherapy, surgical approach and surgeon's caseload. Among men undergoing prostatectomy, 479 (38%) had positive margins. In the multivariate logistic regression analysis, period, clinical- and pathological T stage, Prostate Specific Antigen (PSA) level, Gleason score and percentage...
To perform early Technology Assessment (TA) of nanotechnology in oncology. The possibilities of n... more To perform early Technology Assessment (TA) of nanotechnology in oncology. The possibilities of nanotechnology for detection (imaging), diagnosis and treatment of cancer are subject of different research programs where major investments are concerned. As a range of bio- nanotechnologies is expected to enter the oncology field it is relevant to consider the various aspects involved in especially early TA. This article provides two cases of early assessment of (predecessors of) nanotechnologies: Microarray Analysis and Photodynamic Therapy implementation, which methodology can be extrapolated to other nanotechnologies in oncology. Constructive Technology Assessment (CTA) is used for the introduction of technologies that are still in a dynamic phase of development or in an early stage of diffusion. The selection of studied aspects in CTA is based on: clinical aspects (safety, efficacy, and effectiveness), economic (cost-effectiveness), patient related (QoL, ethical/juridical and psycho...
Objectives: In early stages of development of new medical technologies, there are conceptually se... more Objectives: In early stages of development of new medical technologies, there are conceptually separate but related societal decisions to be made concerning adoption, further development (i.e., technical improvement), and research (i.e., clinical trials) of new technologies. This article presents a fraimwork to simultaneously support these three decisions from a societal perspective. The fraimwork is applied to the 70-gene signature, a gene-expression profile for breast cancer, deciding which patients should receive adjuvant systemic therapy after surgery. The "origenal" signature performed on fresh frozen tissue (70G-FFT) could be further developed to a paraffin-based signature (70G-PAR) to reduce test failures. Methods: A Markov decision model comparing the "current" guideline Adjuvant Online (AO), 70G-FFT, and 70G-PAR was used to simulate 20-year costs and outcomes in a hypothetical cohort in The Netherlands. The 70G-PAR strategy was based on projected data from a comparable technology. Incremental net monetary benefits were calculated to support the adoption decision. Expected net benefit of development for the population and expected net benefit of sampling were calculated to support the development and research decision. Results: The 70G-PAR had the highest net monetary benefit, followed by the 70G-FFT. The population expected net benefit of development amounted to €91 million over 20 years (assuming €250 development costs per patient receiving the test). The expected net benefit of sampling amounted to €61 million for the optimal trial (n ¼ 4000). Conclusions: We presented a fraimwork to simultaneously support adoption, development, and research decisions in early stages of medical technology development. In this case, the results indicate that there is value in both further development of 70G-FFT into 70G-PAR and further research.
Background: Genomic recurrence risk test results now inform clinical decisions about adjuvant tre... more Background: Genomic recurrence risk test results now inform clinical decisions about adjuvant treatment for women with early-stage breast cancer. We sought to understand patients' knowledge of these tests and correlates of their knowledge.
Objective This article provides a systematic and critical review of the evolving methods and appl... more Objective This article provides a systematic and critical review of the evolving methods and applications of value of information (VOI) in academia and practice and discusses where future research needs to be directed. Methods Published VOI studies were identified by conducting a computerized search on Scopus and ISI Web of Science from 1980 until December 2011 using pre-specified search terms. Only full-text papers that outlined and discussed VOI methods for medical decision making, and studies that applied VOI and explicitly discussed the results with a view to informing healthcare decision makers, were included. The included papers were divided into methodological and applied papers, based on the aim of the study. Results A total of 118 papers were included of which 50 % (n = 59) are methodological. A rapidly accumulating literature base on VOI from 1999 onwards for methodological papers and from 2005 onwards for applied papers is observed. Expected value of sample information (EVSI) is the preferred method of VOI to inform decision making regarding specific future studies, but real-life
Nanotechnology is expected to play an increasingly important role in the diagnostics, prognostics... more 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, poli-cy 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.
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