Prof. Dr. med. Thomas Szucs Department of Public Health Profiles & Affiliations OverviewResearch Publications Projects & Collaborations Projects & Collaborations OverviewResearch Publications Projects & Collaborations Profiles & Affiliations Projects & Collaborations 15 foundShow per page10 10 20 50 ENDOSCAPE, a clinically applicable non-viral gene delivery technology Research Project | 2 Project MembersGene therapy is one of the most promising treatment options for future advanced therapies in a broad range of diseases. Successful gene delivery requires the recognition of target cells as well as cytosolic and nucleosolic uptake of the gene. Currently, non-viral based gene delivery such as transfection reagents are only suitable for in vitro applications and clinical gene therapeutics delivery is accomplished via viral vectors, which still has major safety concerns and complex and costly manufacturing procedures, preventing future implementation for the treatment of diseases with large patients groups. In the last 15 years, a class of secondary plant metabolites has been discovered that selectively mediates endosomal escape and cytoplasmic delivery of macromolecules only at low endosomal pH, thereby inducing a 40-fold enhanced gene delivery efficacy, in vivo . The currently employed methods of applying endosomal escape enhancers and gene therapeutic product, however, do not ensure that both compounds are at the same time at the site of interaction. The ENDOSCAPE technology platform will develop and collect proof of concept for a non-viral gene delivery technology with increased synchronization (in time and place) of both compounds. Proof of concept of the ENDOSCAPE technology has a major impact on the therapeutic opportunities for current and future macromolecule drugs for a broad range of diseases. All this induces new biotech-based businesses; new research projects and creates new technology platforms for development of new macromolecule therapeutics for a broad range of disease indications. The non-viral bases ENDOSCAPE technology will enhance therapeutic efficacy with lower therapeutic dose thereby reducing costs of healthcare, improving the health of patients worldwide, and strengthening the competitive landscape of the EU in the worldwide quest for such an advanced technology. Cost-effectiveness of novel multiple sclerosis drug Research Project | 4 Project MembersAssessment of cost-effectiveness of a novel multiple sclerosis drug, from the perspective of the Swiss statutory health insurance and Swiss healthcare system. Impact of targeted therapy in patients with metastatic lung cancer Research Project | 3 Project MembersCost effectiveness of pembrolizumab vs chemotherapy as first-line treatment for metastatic NSCLC that expresses high levels of PD-L1 in Switzerland Aim The study aim was to evaluate the cost-effectiveness of pembrolizumab monotherapy compared to chemotherapy as a first-line treatment for previously untreated metastatic non-small cell lung cancer (NSCLC) with PD-L1 tumour proportion score (TPS) ≥50%, from a Swiss payer perspective. Cost-effectiveness of pembrolizumab for this indication has not previously been evaluated in Switzerland. Methods We conducted an analysis using a partitioned survival model with a cycle length of one week, basecase time horizon of 20 years and discount rate of 3% for cost and health outcomes. KEYNOTE-024 randomised controlled trial data of pembrolizumab monotherapy compared to chemotherapy was used as a basis for projecting time-on-treatment, progression-free survival and overall survival outcomes, over a 20 year period. For overall survival and progression-free survival, we used Kaplan-Meier probabilities for a brief initial period of the model, followed by parametric curves which had the best fit with subsequent trial data. Quality-adjusted life years (QALYs) were calculated based on the EuroQol 5-dimensional 3-level (EQ-5D-3L) questionnaire administered to trial patients. Costs (Swiss Franc (CHF), year 2018) of drug acquisition/administration, adverse events and disease management were included. Results For the base-case, pembrolizumab monotherapy resulted in mean incremental costs of CHF 77,060 (pembrolizumab: CHF 223,324, chemotherapy: CHF 146,264) and mean incremental QALYs of 1.34 (pembrolizumab: 3.05, chemotherapy: 1.71), leading to an incremental cost-effectiveness ratio of CHF 57,402 per QALY gained. Cost-effectiveness results were most sensitive to overall survival parameters and relatively insensitive to other parameters varied. In probabilistic sensitivity analysis, the probability of cost-effectiveness of pembrolizumab assuming a willingness-to-pay threshold of CHF 100,000 per QALY gained, was 88%. Conclusion Pembrolizumab is likely to be cost-effective for treating Swiss patients with previously untreated metastatic NSCLC expressing PD-L1 TPS≥50%. This economic evaluation was based on the KEYNOTE-024 trial. The trial identifier is NCT02142738. (Swiss Med Wkly 2019;149:w20170. doi: 10.4414/smw.2019.20170. eCollection 2019 Dec 16) Cost-effectiveness of hyperkalemia treatment Research Project | 4 Project MembersAn increase in blood-serum-potassium levels (hyperkalemia) is common in patients with renal impairment or heart failure. Indicated drug treatments, namely RAAS-inhibitors, (RAASi) such as ACE inhibitors, AT1 receptor-antagonists and aldosterone-blockers, lead to a further rise in potassium levels and may need to be discontinued despite their favourable cardiac and renal effects. Patiromer is an oral drug that can be used to treat latent/chronic hyperkalemia, reduce the risk of acute episodes of hyperkalemia, and enable the continuation of RAASi treatment. Based on clinical trial data, published literature and expert input, we have developed a decision-analytic model, composed of a decision-tree and a semi-Markov module, to evaluate the health economic properties of treatment with patiromer, for European countries. Cost of HCV treatment in Switzerland Research Project | 3 Project MembersFeasibility assessment for a study to assess the cost of hepatatis C treatment in Switzerland. Effect of the Swiss human research legislation on the costs associated with randomized clinical trials in Switzerland Research Project | 3 Project MembersIn any medical and health related field there is often uncertainty from which of two or more available treatment options a patient would profit most. Allocating groups of patients randomly to different treatment options in the context of so-called randomised controlled trials (RCTs) provides the most reliable comparisons and evidence for decision making in clinical practice. However, the conduct of RCTs is costly, administratively burdensome and highly regulated to protect study participants. The conduct of an RCT does not only consist of patient enrolment, treatment and follow-up, but also of a comprehensive preparation phase, during which multiple tasks have to be accomplished. For example, a study protocol and a number of other documents need to be created, approval from research ethics committees (RECs) and in some cases from the Swiss Agency for Therapeutic Products ( Swissmedic ) has to be obtained. To create favourable research conditions in Switzerland, the new law on research with human beings (Human Research Act) and its ordinances, jointly abbreviated in this report as Swiss Legislation on Human Research (LHR), was enacted in January 2014. The main aim of this study was to assess if the new LHR had an impact on the administrative burden and costs to plan and prepare an RCT. To find out about required working efforts and costs to plan and prepare an RCT, we contacted investigators from RCTs which were approved by Swiss RECs in 2012 and 2016 (before and after the implementation of the LHR). Investigators received a comprehensive excel sheet in which all possible preparation steps for an RCT were listed. They were asked to retrospectively estimate the working efforts for all involved staff members and to give information about fixed costs. Based on this information, we aimed to calculate the working efforts and the costs to plan and prepare an RCT. Furthermore, we assessed approval times (i.e. times from submission of study documents until final approval) by RECs and Swissmedic. We received complete resource use and cost data for the preparation phase of 18 RCTs which were approved in 2012 and of 35 RCTs which were approved in 2016. The median working time to plan and prepare an RCT was 113 days (25 th to 75 th percentile range [IQR]: 51-190 days) in 2012 and 133 days (IQR: 79-239 days) in 2016. The median costs to plan and prepare these RCTs were estimated to be CHF 81'100 (IQR: CHF 69'500-123'100) in 2012 and CHF 73'800 (IQR: CHF 43'500-176'700) in 2016. Given the small number of RCTs for which we received data and a strong possibility of selection effects, it was not possible to draw firm conclusions on a cost impact of the LHR. Approval times from RECs were available for a total of 183 RCTs approved in 2012 and 217 RCTs approved in 2016. The median time from application to approval was 72 days (IQR: 41-72 days) in 2012 and 109 days (IQR: 79-154 days) in 2016. Further data provided by Swissmedic indicated that Swissmedic approval times for clinical trials (not only RCTs) were also longer in 2016 (median: 27.0 days; IQR: 19.0-50.5 days) than in 2012 (median: 49.0 days; IQR: 36.0-67.0 days). Gathering actual resource use and cost data for RCTs was difficult, because such information was not systematically documented and it required active collaboration of RCT investigators to comprehensively capture spent resources. Due to the sparseness of the available data, we could not draw firm conclusions regarding changes in the working efforts and costs for the preparation phases of RCTs. Approval times by RECs and Swissmedic were higher in 2016 compared to 2012. However, it is difficult to differentiate whether these differences were due to the LHR or due to other reasons. OPERAM: Optimising PharmacothERApy in the Multimorbid elderly Research Project | 3 Project MembersThe overall aim of OPERAM (OPtimising thERapy to prevent Avoidable hospital admissions in the Multimorbid elderly) is to optimise existing pharmacological and non-pharmacological therapy primarily in order to reduce avoidable hospital admissions among the elderly population aged ≥70 years with multimorbidity. Specifically, the OPERAM consortium aims at: Creating new evidence to prevent avoidable hospital admissions through optimising pharmacotherapy in the multimorbid elderly by performing a multi-centre cluster randomised clinical trial (RCT) to assess the impact of a structured medication review Obtaining evidence-based data comparing pharmacological and non-pharmacological interventions to prevent common causes of avoidable hospital admissions in the elderly with multimorbidity, and rank these interventions according to their effectiveness and safety using network meta-analyses (NMA) Identify the most cost-effective pharmacological and non-pharmacological interventions to prevent avoidable hospital admissions in the multimorbid elderly Cost-effectivness of chronic heart failure treatment Research Project | 2 Project MembersAssessment of the cost-effectiveness of a novel chronic heart failure treatment, from a Swiss perspective. Cost-effectiveness analysis of acute heart failure treatment Research Project | 2 Project MembersCost-effectiveness analysis of serelaxin in the treatment of acute heart failure Genome-based biomarkers leading to validated molecular diagnostic tests for response prediction in breast cancer Research Project | 3 Project MembersObjectives of the WP: WP7 aims at developing the existing analytical framework further and applying it to novel (discovered by the RESPONSIFY consortium) and already available biomarkers. On this basis, health economic characteristics will be defined and we will begin generating an evidence base to sustain efficient decision making on novel test assays in breast cancer management. Currently known markers will also be assessed and different treatment settings (adjuvant, neoadjuvant, metastatic) can be addressed as relevant. It is planned to establish a core health economic model (Markov model) for European countries as a basis for comparing different testing strategies for various biomarkers in breast cancer patients (and potentially, other indications). Clinically useful predictive tests with reasonable sensitivity and specificity to predict drug-response are one cornerstone in achieving a cost? effective implementation of new treatment strategies in oncology. The main advance is the identification of the most effective diagnostic and testing regimens from a health economic point of view. 12 12 OverviewResearch Publications Projects & Collaborations
Projects & Collaborations 15 foundShow per page10 10 20 50 ENDOSCAPE, a clinically applicable non-viral gene delivery technology Research Project | 2 Project MembersGene therapy is one of the most promising treatment options for future advanced therapies in a broad range of diseases. Successful gene delivery requires the recognition of target cells as well as cytosolic and nucleosolic uptake of the gene. Currently, non-viral based gene delivery such as transfection reagents are only suitable for in vitro applications and clinical gene therapeutics delivery is accomplished via viral vectors, which still has major safety concerns and complex and costly manufacturing procedures, preventing future implementation for the treatment of diseases with large patients groups. In the last 15 years, a class of secondary plant metabolites has been discovered that selectively mediates endosomal escape and cytoplasmic delivery of macromolecules only at low endosomal pH, thereby inducing a 40-fold enhanced gene delivery efficacy, in vivo . The currently employed methods of applying endosomal escape enhancers and gene therapeutic product, however, do not ensure that both compounds are at the same time at the site of interaction. The ENDOSCAPE technology platform will develop and collect proof of concept for a non-viral gene delivery technology with increased synchronization (in time and place) of both compounds. Proof of concept of the ENDOSCAPE technology has a major impact on the therapeutic opportunities for current and future macromolecule drugs for a broad range of diseases. All this induces new biotech-based businesses; new research projects and creates new technology platforms for development of new macromolecule therapeutics for a broad range of disease indications. The non-viral bases ENDOSCAPE technology will enhance therapeutic efficacy with lower therapeutic dose thereby reducing costs of healthcare, improving the health of patients worldwide, and strengthening the competitive landscape of the EU in the worldwide quest for such an advanced technology. Cost-effectiveness of novel multiple sclerosis drug Research Project | 4 Project MembersAssessment of cost-effectiveness of a novel multiple sclerosis drug, from the perspective of the Swiss statutory health insurance and Swiss healthcare system. Impact of targeted therapy in patients with metastatic lung cancer Research Project | 3 Project MembersCost effectiveness of pembrolizumab vs chemotherapy as first-line treatment for metastatic NSCLC that expresses high levels of PD-L1 in Switzerland Aim The study aim was to evaluate the cost-effectiveness of pembrolizumab monotherapy compared to chemotherapy as a first-line treatment for previously untreated metastatic non-small cell lung cancer (NSCLC) with PD-L1 tumour proportion score (TPS) ≥50%, from a Swiss payer perspective. Cost-effectiveness of pembrolizumab for this indication has not previously been evaluated in Switzerland. Methods We conducted an analysis using a partitioned survival model with a cycle length of one week, basecase time horizon of 20 years and discount rate of 3% for cost and health outcomes. KEYNOTE-024 randomised controlled trial data of pembrolizumab monotherapy compared to chemotherapy was used as a basis for projecting time-on-treatment, progression-free survival and overall survival outcomes, over a 20 year period. For overall survival and progression-free survival, we used Kaplan-Meier probabilities for a brief initial period of the model, followed by parametric curves which had the best fit with subsequent trial data. Quality-adjusted life years (QALYs) were calculated based on the EuroQol 5-dimensional 3-level (EQ-5D-3L) questionnaire administered to trial patients. Costs (Swiss Franc (CHF), year 2018) of drug acquisition/administration, adverse events and disease management were included. Results For the base-case, pembrolizumab monotherapy resulted in mean incremental costs of CHF 77,060 (pembrolizumab: CHF 223,324, chemotherapy: CHF 146,264) and mean incremental QALYs of 1.34 (pembrolizumab: 3.05, chemotherapy: 1.71), leading to an incremental cost-effectiveness ratio of CHF 57,402 per QALY gained. Cost-effectiveness results were most sensitive to overall survival parameters and relatively insensitive to other parameters varied. In probabilistic sensitivity analysis, the probability of cost-effectiveness of pembrolizumab assuming a willingness-to-pay threshold of CHF 100,000 per QALY gained, was 88%. Conclusion Pembrolizumab is likely to be cost-effective for treating Swiss patients with previously untreated metastatic NSCLC expressing PD-L1 TPS≥50%. This economic evaluation was based on the KEYNOTE-024 trial. The trial identifier is NCT02142738. (Swiss Med Wkly 2019;149:w20170. doi: 10.4414/smw.2019.20170. eCollection 2019 Dec 16) Cost-effectiveness of hyperkalemia treatment Research Project | 4 Project MembersAn increase in blood-serum-potassium levels (hyperkalemia) is common in patients with renal impairment or heart failure. Indicated drug treatments, namely RAAS-inhibitors, (RAASi) such as ACE inhibitors, AT1 receptor-antagonists and aldosterone-blockers, lead to a further rise in potassium levels and may need to be discontinued despite their favourable cardiac and renal effects. Patiromer is an oral drug that can be used to treat latent/chronic hyperkalemia, reduce the risk of acute episodes of hyperkalemia, and enable the continuation of RAASi treatment. Based on clinical trial data, published literature and expert input, we have developed a decision-analytic model, composed of a decision-tree and a semi-Markov module, to evaluate the health economic properties of treatment with patiromer, for European countries. Cost of HCV treatment in Switzerland Research Project | 3 Project MembersFeasibility assessment for a study to assess the cost of hepatatis C treatment in Switzerland. Effect of the Swiss human research legislation on the costs associated with randomized clinical trials in Switzerland Research Project | 3 Project MembersIn any medical and health related field there is often uncertainty from which of two or more available treatment options a patient would profit most. Allocating groups of patients randomly to different treatment options in the context of so-called randomised controlled trials (RCTs) provides the most reliable comparisons and evidence for decision making in clinical practice. However, the conduct of RCTs is costly, administratively burdensome and highly regulated to protect study participants. The conduct of an RCT does not only consist of patient enrolment, treatment and follow-up, but also of a comprehensive preparation phase, during which multiple tasks have to be accomplished. For example, a study protocol and a number of other documents need to be created, approval from research ethics committees (RECs) and in some cases from the Swiss Agency for Therapeutic Products ( Swissmedic ) has to be obtained. To create favourable research conditions in Switzerland, the new law on research with human beings (Human Research Act) and its ordinances, jointly abbreviated in this report as Swiss Legislation on Human Research (LHR), was enacted in January 2014. The main aim of this study was to assess if the new LHR had an impact on the administrative burden and costs to plan and prepare an RCT. To find out about required working efforts and costs to plan and prepare an RCT, we contacted investigators from RCTs which were approved by Swiss RECs in 2012 and 2016 (before and after the implementation of the LHR). Investigators received a comprehensive excel sheet in which all possible preparation steps for an RCT were listed. They were asked to retrospectively estimate the working efforts for all involved staff members and to give information about fixed costs. Based on this information, we aimed to calculate the working efforts and the costs to plan and prepare an RCT. Furthermore, we assessed approval times (i.e. times from submission of study documents until final approval) by RECs and Swissmedic. We received complete resource use and cost data for the preparation phase of 18 RCTs which were approved in 2012 and of 35 RCTs which were approved in 2016. The median working time to plan and prepare an RCT was 113 days (25 th to 75 th percentile range [IQR]: 51-190 days) in 2012 and 133 days (IQR: 79-239 days) in 2016. The median costs to plan and prepare these RCTs were estimated to be CHF 81'100 (IQR: CHF 69'500-123'100) in 2012 and CHF 73'800 (IQR: CHF 43'500-176'700) in 2016. Given the small number of RCTs for which we received data and a strong possibility of selection effects, it was not possible to draw firm conclusions on a cost impact of the LHR. Approval times from RECs were available for a total of 183 RCTs approved in 2012 and 217 RCTs approved in 2016. The median time from application to approval was 72 days (IQR: 41-72 days) in 2012 and 109 days (IQR: 79-154 days) in 2016. Further data provided by Swissmedic indicated that Swissmedic approval times for clinical trials (not only RCTs) were also longer in 2016 (median: 27.0 days; IQR: 19.0-50.5 days) than in 2012 (median: 49.0 days; IQR: 36.0-67.0 days). Gathering actual resource use and cost data for RCTs was difficult, because such information was not systematically documented and it required active collaboration of RCT investigators to comprehensively capture spent resources. Due to the sparseness of the available data, we could not draw firm conclusions regarding changes in the working efforts and costs for the preparation phases of RCTs. Approval times by RECs and Swissmedic were higher in 2016 compared to 2012. However, it is difficult to differentiate whether these differences were due to the LHR or due to other reasons. OPERAM: Optimising PharmacothERApy in the Multimorbid elderly Research Project | 3 Project MembersThe overall aim of OPERAM (OPtimising thERapy to prevent Avoidable hospital admissions in the Multimorbid elderly) is to optimise existing pharmacological and non-pharmacological therapy primarily in order to reduce avoidable hospital admissions among the elderly population aged ≥70 years with multimorbidity. Specifically, the OPERAM consortium aims at: Creating new evidence to prevent avoidable hospital admissions through optimising pharmacotherapy in the multimorbid elderly by performing a multi-centre cluster randomised clinical trial (RCT) to assess the impact of a structured medication review Obtaining evidence-based data comparing pharmacological and non-pharmacological interventions to prevent common causes of avoidable hospital admissions in the elderly with multimorbidity, and rank these interventions according to their effectiveness and safety using network meta-analyses (NMA) Identify the most cost-effective pharmacological and non-pharmacological interventions to prevent avoidable hospital admissions in the multimorbid elderly Cost-effectivness of chronic heart failure treatment Research Project | 2 Project MembersAssessment of the cost-effectiveness of a novel chronic heart failure treatment, from a Swiss perspective. Cost-effectiveness analysis of acute heart failure treatment Research Project | 2 Project MembersCost-effectiveness analysis of serelaxin in the treatment of acute heart failure Genome-based biomarkers leading to validated molecular diagnostic tests for response prediction in breast cancer Research Project | 3 Project MembersObjectives of the WP: WP7 aims at developing the existing analytical framework further and applying it to novel (discovered by the RESPONSIFY consortium) and already available biomarkers. On this basis, health economic characteristics will be defined and we will begin generating an evidence base to sustain efficient decision making on novel test assays in breast cancer management. Currently known markers will also be assessed and different treatment settings (adjuvant, neoadjuvant, metastatic) can be addressed as relevant. It is planned to establish a core health economic model (Markov model) for European countries as a basis for comparing different testing strategies for various biomarkers in breast cancer patients (and potentially, other indications). Clinically useful predictive tests with reasonable sensitivity and specificity to predict drug-response are one cornerstone in achieving a cost? effective implementation of new treatment strategies in oncology. The main advance is the identification of the most effective diagnostic and testing regimens from a health economic point of view. 12 12
ENDOSCAPE, a clinically applicable non-viral gene delivery technology Research Project | 2 Project MembersGene therapy is one of the most promising treatment options for future advanced therapies in a broad range of diseases. Successful gene delivery requires the recognition of target cells as well as cytosolic and nucleosolic uptake of the gene. Currently, non-viral based gene delivery such as transfection reagents are only suitable for in vitro applications and clinical gene therapeutics delivery is accomplished via viral vectors, which still has major safety concerns and complex and costly manufacturing procedures, preventing future implementation for the treatment of diseases with large patients groups. In the last 15 years, a class of secondary plant metabolites has been discovered that selectively mediates endosomal escape and cytoplasmic delivery of macromolecules only at low endosomal pH, thereby inducing a 40-fold enhanced gene delivery efficacy, in vivo . The currently employed methods of applying endosomal escape enhancers and gene therapeutic product, however, do not ensure that both compounds are at the same time at the site of interaction. The ENDOSCAPE technology platform will develop and collect proof of concept for a non-viral gene delivery technology with increased synchronization (in time and place) of both compounds. Proof of concept of the ENDOSCAPE technology has a major impact on the therapeutic opportunities for current and future macromolecule drugs for a broad range of diseases. All this induces new biotech-based businesses; new research projects and creates new technology platforms for development of new macromolecule therapeutics for a broad range of disease indications. The non-viral bases ENDOSCAPE technology will enhance therapeutic efficacy with lower therapeutic dose thereby reducing costs of healthcare, improving the health of patients worldwide, and strengthening the competitive landscape of the EU in the worldwide quest for such an advanced technology.
Cost-effectiveness of novel multiple sclerosis drug Research Project | 4 Project MembersAssessment of cost-effectiveness of a novel multiple sclerosis drug, from the perspective of the Swiss statutory health insurance and Swiss healthcare system.
Impact of targeted therapy in patients with metastatic lung cancer Research Project | 3 Project MembersCost effectiveness of pembrolizumab vs chemotherapy as first-line treatment for metastatic NSCLC that expresses high levels of PD-L1 in Switzerland Aim The study aim was to evaluate the cost-effectiveness of pembrolizumab monotherapy compared to chemotherapy as a first-line treatment for previously untreated metastatic non-small cell lung cancer (NSCLC) with PD-L1 tumour proportion score (TPS) ≥50%, from a Swiss payer perspective. Cost-effectiveness of pembrolizumab for this indication has not previously been evaluated in Switzerland. Methods We conducted an analysis using a partitioned survival model with a cycle length of one week, basecase time horizon of 20 years and discount rate of 3% for cost and health outcomes. KEYNOTE-024 randomised controlled trial data of pembrolizumab monotherapy compared to chemotherapy was used as a basis for projecting time-on-treatment, progression-free survival and overall survival outcomes, over a 20 year period. For overall survival and progression-free survival, we used Kaplan-Meier probabilities for a brief initial period of the model, followed by parametric curves which had the best fit with subsequent trial data. Quality-adjusted life years (QALYs) were calculated based on the EuroQol 5-dimensional 3-level (EQ-5D-3L) questionnaire administered to trial patients. Costs (Swiss Franc (CHF), year 2018) of drug acquisition/administration, adverse events and disease management were included. Results For the base-case, pembrolizumab monotherapy resulted in mean incremental costs of CHF 77,060 (pembrolizumab: CHF 223,324, chemotherapy: CHF 146,264) and mean incremental QALYs of 1.34 (pembrolizumab: 3.05, chemotherapy: 1.71), leading to an incremental cost-effectiveness ratio of CHF 57,402 per QALY gained. Cost-effectiveness results were most sensitive to overall survival parameters and relatively insensitive to other parameters varied. In probabilistic sensitivity analysis, the probability of cost-effectiveness of pembrolizumab assuming a willingness-to-pay threshold of CHF 100,000 per QALY gained, was 88%. Conclusion Pembrolizumab is likely to be cost-effective for treating Swiss patients with previously untreated metastatic NSCLC expressing PD-L1 TPS≥50%. This economic evaluation was based on the KEYNOTE-024 trial. The trial identifier is NCT02142738. (Swiss Med Wkly 2019;149:w20170. doi: 10.4414/smw.2019.20170. eCollection 2019 Dec 16)
Cost-effectiveness of hyperkalemia treatment Research Project | 4 Project MembersAn increase in blood-serum-potassium levels (hyperkalemia) is common in patients with renal impairment or heart failure. Indicated drug treatments, namely RAAS-inhibitors, (RAASi) such as ACE inhibitors, AT1 receptor-antagonists and aldosterone-blockers, lead to a further rise in potassium levels and may need to be discontinued despite their favourable cardiac and renal effects. Patiromer is an oral drug that can be used to treat latent/chronic hyperkalemia, reduce the risk of acute episodes of hyperkalemia, and enable the continuation of RAASi treatment. Based on clinical trial data, published literature and expert input, we have developed a decision-analytic model, composed of a decision-tree and a semi-Markov module, to evaluate the health economic properties of treatment with patiromer, for European countries.
Cost of HCV treatment in Switzerland Research Project | 3 Project MembersFeasibility assessment for a study to assess the cost of hepatatis C treatment in Switzerland.
Effect of the Swiss human research legislation on the costs associated with randomized clinical trials in Switzerland Research Project | 3 Project MembersIn any medical and health related field there is often uncertainty from which of two or more available treatment options a patient would profit most. Allocating groups of patients randomly to different treatment options in the context of so-called randomised controlled trials (RCTs) provides the most reliable comparisons and evidence for decision making in clinical practice. However, the conduct of RCTs is costly, administratively burdensome and highly regulated to protect study participants. The conduct of an RCT does not only consist of patient enrolment, treatment and follow-up, but also of a comprehensive preparation phase, during which multiple tasks have to be accomplished. For example, a study protocol and a number of other documents need to be created, approval from research ethics committees (RECs) and in some cases from the Swiss Agency for Therapeutic Products ( Swissmedic ) has to be obtained. To create favourable research conditions in Switzerland, the new law on research with human beings (Human Research Act) and its ordinances, jointly abbreviated in this report as Swiss Legislation on Human Research (LHR), was enacted in January 2014. The main aim of this study was to assess if the new LHR had an impact on the administrative burden and costs to plan and prepare an RCT. To find out about required working efforts and costs to plan and prepare an RCT, we contacted investigators from RCTs which were approved by Swiss RECs in 2012 and 2016 (before and after the implementation of the LHR). Investigators received a comprehensive excel sheet in which all possible preparation steps for an RCT were listed. They were asked to retrospectively estimate the working efforts for all involved staff members and to give information about fixed costs. Based on this information, we aimed to calculate the working efforts and the costs to plan and prepare an RCT. Furthermore, we assessed approval times (i.e. times from submission of study documents until final approval) by RECs and Swissmedic. We received complete resource use and cost data for the preparation phase of 18 RCTs which were approved in 2012 and of 35 RCTs which were approved in 2016. The median working time to plan and prepare an RCT was 113 days (25 th to 75 th percentile range [IQR]: 51-190 days) in 2012 and 133 days (IQR: 79-239 days) in 2016. The median costs to plan and prepare these RCTs were estimated to be CHF 81'100 (IQR: CHF 69'500-123'100) in 2012 and CHF 73'800 (IQR: CHF 43'500-176'700) in 2016. Given the small number of RCTs for which we received data and a strong possibility of selection effects, it was not possible to draw firm conclusions on a cost impact of the LHR. Approval times from RECs were available for a total of 183 RCTs approved in 2012 and 217 RCTs approved in 2016. The median time from application to approval was 72 days (IQR: 41-72 days) in 2012 and 109 days (IQR: 79-154 days) in 2016. Further data provided by Swissmedic indicated that Swissmedic approval times for clinical trials (not only RCTs) were also longer in 2016 (median: 27.0 days; IQR: 19.0-50.5 days) than in 2012 (median: 49.0 days; IQR: 36.0-67.0 days). Gathering actual resource use and cost data for RCTs was difficult, because such information was not systematically documented and it required active collaboration of RCT investigators to comprehensively capture spent resources. Due to the sparseness of the available data, we could not draw firm conclusions regarding changes in the working efforts and costs for the preparation phases of RCTs. Approval times by RECs and Swissmedic were higher in 2016 compared to 2012. However, it is difficult to differentiate whether these differences were due to the LHR or due to other reasons.
OPERAM: Optimising PharmacothERApy in the Multimorbid elderly Research Project | 3 Project MembersThe overall aim of OPERAM (OPtimising thERapy to prevent Avoidable hospital admissions in the Multimorbid elderly) is to optimise existing pharmacological and non-pharmacological therapy primarily in order to reduce avoidable hospital admissions among the elderly population aged ≥70 years with multimorbidity. Specifically, the OPERAM consortium aims at: Creating new evidence to prevent avoidable hospital admissions through optimising pharmacotherapy in the multimorbid elderly by performing a multi-centre cluster randomised clinical trial (RCT) to assess the impact of a structured medication review Obtaining evidence-based data comparing pharmacological and non-pharmacological interventions to prevent common causes of avoidable hospital admissions in the elderly with multimorbidity, and rank these interventions according to their effectiveness and safety using network meta-analyses (NMA) Identify the most cost-effective pharmacological and non-pharmacological interventions to prevent avoidable hospital admissions in the multimorbid elderly
Cost-effectivness of chronic heart failure treatment Research Project | 2 Project MembersAssessment of the cost-effectiveness of a novel chronic heart failure treatment, from a Swiss perspective.
Cost-effectiveness analysis of acute heart failure treatment Research Project | 2 Project MembersCost-effectiveness analysis of serelaxin in the treatment of acute heart failure
Genome-based biomarkers leading to validated molecular diagnostic tests for response prediction in breast cancer Research Project | 3 Project MembersObjectives of the WP: WP7 aims at developing the existing analytical framework further and applying it to novel (discovered by the RESPONSIFY consortium) and already available biomarkers. On this basis, health economic characteristics will be defined and we will begin generating an evidence base to sustain efficient decision making on novel test assays in breast cancer management. Currently known markers will also be assessed and different treatment settings (adjuvant, neoadjuvant, metastatic) can be addressed as relevant. It is planned to establish a core health economic model (Markov model) for European countries as a basis for comparing different testing strategies for various biomarkers in breast cancer patients (and potentially, other indications). Clinically useful predictive tests with reasonable sensitivity and specificity to predict drug-response are one cornerstone in achieving a cost? effective implementation of new treatment strategies in oncology. The main advance is the identification of the most effective diagnostic and testing regimens from a health economic point of view.
