Time: 15:00 - 17:00 UK time
The paper to be presented appeared earlier this year in Pharmaceutical Statistics (Weber, Hemmings, Koch, 17, 329-341) and is motivated by the opportunities and challenges for using Bayesian methods with informative priors to support drug development and licencing when only a small pool of patients is available, as in the case of rare diseases and paediatric population. With a small study population, meeting the expected level of evidence required for regulatory approval can be challenging. The specific focus of the paper is on the use of data‐based priors in the decision-making process of paediatric extrapolation, and results are presented comparing different frequentist and Bayesian meta-analytic methods for combining adult and paediatric data.
In this webinar, the authors will present their paper, followed by discussion on:
- Scientific rationale for borrowing existing data to make inference about drug effects under different settings: rare diseases, extrapolation and use of historical controls.
- Other methods for combining historical and prospective data beyond standard meta-analytic approaches (e.g., robust MAP priors).
- Ways in which the Bayesian strategy could be supplemented or adapted to enable the independent contribution of the new trial data to be formally quantified and assessed.
We are pleased to announce that the meeting will be chaired by Byron Jones (Novartis)
 |
Kristina Weber (Institute for Biostatistics, Hannover Medical School) Kristina Weber is since 2014 a research associate at the Institute of Biostatistics, Hannover Medical School. Her research interests are in the development of efficient and effective research strategies in limited populations. Her PhD thesis focuses on the application of Bayesian methods in paediatric and rare diseases extrapolation concepts. She has joined Roche in November 2018. |
 |
Rob Hemmings (MHRA) Rob has been with the Licensing Division within MHRA for approaching 19 years, has been a co-opted member of CHMP for 11 years; chair of the EMA’s SAWP for the past 8 years; first chair and then member of the EMA’s BSWP since its inception. |
 |
Armin Koch (Institute for Biostatistics, Hannover Medical School) Professor Armin Koch studied mathematics and chemistry at Heidelberg University, has been a research assistant at the German Centre for the Research on Cancer (DKFZ) between 1984 and 1991. Thereafter he has been an employee at the Institute of Medical Biometry at Heidelberg University until in 1999 when he joined the Federal Institute for Drugs and Medical Devices (BfArM) in Germany. From 2001 to 2008 he was head of the unit „Biostatistics and Experimental Design“. Since 2008 he is Director of the Institute for Biostatistics at Hannover Medical School. Prof. Koch is a member of the Scientific Advice Working Party (SAWP) and the Biostatistics working party (BSWP) at the European Medicines Agency (EMA) and has been a member of the International Council for Harmonisation ICH-E17 working group. |
Discussants:
 |
Nicky Best (GSK) (on behalf of the EFSPI/PSI Historical Data SIG) Nicky Best was an academic statistician for 20 years, starting out at the Medical Research Council Biostatistics Unit in Cambridge, UK before moving to Imperial College London, where she was professor of Statistics and Epidemiology. Her research interests focused around the development and application of Bayesian methods in health and social science, and she is a co-developer of the BUGS Bayesian software package. In 2014 she moved to GlaxoSmithKline (GSK), where she is Head of the Advanced Biostatistics and Data Analytics group. She was awarded the RSS/PSI award for Statistical Excellence in the Pharmaceutical Industry in 2015 for her leading role in implementing expert prior elicitation methods and statistical assurance calculations to improve decision making in clinical development at GSK, and the RSS Bradford Hill Medal in 2018 for her contributions to the exposition and application of Bayesian methods to clinical trials, cost-effectiveness, epidemiology and drug development programmes. |
 |
Lisa LaVange (University of North Carolina, Chapel Hill) Lisa LaVange, PhD, is Professor and Associate Chair of Biostatistics, Gillings School of Global Public Health, UNC-CH. She is also director of the department’s Collaborative Studies Coordinating Center. From 2011 to 2017, Dr. LaVange led the Office of Biostatistics, CDER, FDA, where she directed over 200 statisticians involved in the development and application of statistical methodology for drug regulation. Prior to her government and academic experience, she spent 16 years in non-profit research and 10 years in the pharmaceutical industry. Dr. LaVange is an elected fellow of the American Statistical Association (ASA) and is the 2018 ASA President. |
| Registration | |
| PSI Member | Free |
| Non-member | £20 (plus VAT) |
Time: 15:00 - 17:00 UK time
The paper to be presented appeared earlier this year in Pharmaceutical Statistics (Weber, Hemmings, Koch, 17, 329-341) and is motivated by the opportunities and challenges for using Bayesian methods with informative priors to support drug development and licencing when only a small pool of patients is available, as in the case of rare diseases and paediatric population. With a small study population, meeting the expected level of evidence required for regulatory approval can be challenging. The specific focus of the paper is on the use of data‐based priors in the decision-making process of paediatric extrapolation, and results are presented comparing different frequentist and Bayesian meta-analytic methods for combining adult and paediatric data.
In this webinar, the authors will present their paper, followed by discussion on:
- Scientific rationale for borrowing existing data to make inference about drug effects under different settings: rare diseases, extrapolation and use of historical controls.
- Other methods for combining historical and prospective data beyond standard meta-analytic approaches (e.g., robust MAP priors).
- Ways in which the Bayesian strategy could be supplemented or adapted to enable the independent contribution of the new trial data to be formally quantified and assessed.
We are pleased to announce that the meeting will be chaired by Byron Jones (Novartis)
| |
Kristina Weber (Institute for Biostatistics, Hannover Medical School) Kristina Weber is since 2014 a research associate at the Institute of Biostatistics, Hannover Medical School. Her research interests are in the development of efficient and effective research strategies in limited populations. Her PhD thesis focuses on the application of Bayesian methods in paediatric and rare diseases extrapolation concepts. She has joined Roche in November 2018. |
| |
Rob Hemmings (MHRA) Rob has been with the Licensing Division within MHRA for approaching 19 years, has been a co-opted member of CHMP for 11 years; chair of the EMA’s SAWP for the past 8 years; first chair and then member of the EMA’s BSWP since its inception. |
| |
Armin Koch (Institute for Biostatistics, Hannover Medical School) Professor Armin Koch studied mathematics and chemistry at Heidelberg University, has been a research assistant at the German Centre for the Research on Cancer (DKFZ) between 1984 and 1991. Thereafter he has been an employee at the Institute of Medical Biometry at Heidelberg University until in 1999 when he joined the Federal Institute for Drugs and Medical Devices (BfArM) in Germany. From 2001 to 2008 he was head of the unit „Biostatistics and Experimental Design“. Since 2008 he is Director of the Institute for Biostatistics at Hannover Medical School. Prof. Koch is a member of the Scientific Advice Working Party (SAWP) and the Biostatistics working party (BSWP) at the European Medicines Agency (EMA) and has been a member of the International Council for Harmonisation ICH-E17 working group. |
Discussants:
| |
Nicky Best (GSK) (on behalf of the EFSPI/PSI Historical Data SIG) Nicky Best was an academic statistician for 20 years, starting out at the Medical Research Council Biostatistics Unit in Cambridge, UK before moving to Imperial College London, where she was professor of Statistics and Epidemiology. Her research interests focused around the development and application of Bayesian methods in health and social science, and she is a co-developer of the BUGS Bayesian software package. In 2014 she moved to GlaxoSmithKline (GSK), where she is Head of the Advanced Biostatistics and Data Analytics group. She was awarded the RSS/PSI award for Statistical Excellence in the Pharmaceutical Industry in 2015 for her leading role in implementing expert prior elicitation methods and statistical assurance calculations to improve decision making in clinical development at GSK, and the RSS Bradford Hill Medal in 2018 for her contributions to the exposition and application of Bayesian methods to clinical trials, cost-effectiveness, epidemiology and drug development programmes. |
| |
Lisa LaVange (University of North Carolina, Chapel Hill) Lisa LaVange, PhD, is Professor and Associate Chair of Biostatistics, Gillings School of Global Public Health, UNC-CH. She is also director of the department’s Collaborative Studies Coordinating Center. From 2011 to 2017, Dr. LaVange led the Office of Biostatistics, CDER, FDA, where she directed over 200 statisticians involved in the development and application of statistical methodology for drug regulation. Prior to her government and academic experience, she spent 16 years in non-profit research and 10 years in the pharmaceutical industry. Dr. LaVange is an elected fellow of the American Statistical Association (ASA) and is the 2018 ASA President. |
| Registration | |
| PSI Member | Free |
| Non-member | £20 (plus VAT) |
Time: 15:00 - 17:00 UK time
The paper to be presented appeared earlier this year in Pharmaceutical Statistics (Weber, Hemmings, Koch, 17, 329-341) and is motivated by the opportunities and challenges for using Bayesian methods with informative priors to support drug development and licencing when only a small pool of patients is available, as in the case of rare diseases and paediatric population. With a small study population, meeting the expected level of evidence required for regulatory approval can be challenging. The specific focus of the paper is on the use of data‐based priors in the decision-making process of paediatric extrapolation, and results are presented comparing different frequentist and Bayesian meta-analytic methods for combining adult and paediatric data.
In this webinar, the authors will present their paper, followed by discussion on:
- Scientific rationale for borrowing existing data to make inference about drug effects under different settings: rare diseases, extrapolation and use of historical controls.
- Other methods for combining historical and prospective data beyond standard meta-analytic approaches (e.g., robust MAP priors).
- Ways in which the Bayesian strategy could be supplemented or adapted to enable the independent contribution of the new trial data to be formally quantified and assessed.
We are pleased to announce that the meeting will be chaired by Byron Jones (Novartis)
| |
Kristina Weber (Institute for Biostatistics, Hannover Medical School) Kristina Weber is since 2014 a research associate at the Institute of Biostatistics, Hannover Medical School. Her research interests are in the development of efficient and effective research strategies in limited populations. Her PhD thesis focuses on the application of Bayesian methods in paediatric and rare diseases extrapolation concepts. She has joined Roche in November 2018. |
| |
Rob Hemmings (MHRA) Rob has been with the Licensing Division within MHRA for approaching 19 years, has been a co-opted member of CHMP for 11 years; chair of the EMA’s SAWP for the past 8 years; first chair and then member of the EMA’s BSWP since its inception. |
| |
Armin Koch (Institute for Biostatistics, Hannover Medical School) Professor Armin Koch studied mathematics and chemistry at Heidelberg University, has been a research assistant at the German Centre for the Research on Cancer (DKFZ) between 1984 and 1991. Thereafter he has been an employee at the Institute of Medical Biometry at Heidelberg University until in 1999 when he joined the Federal Institute for Drugs and Medical Devices (BfArM) in Germany. From 2001 to 2008 he was head of the unit „Biostatistics and Experimental Design“. Since 2008 he is Director of the Institute for Biostatistics at Hannover Medical School. Prof. Koch is a member of the Scientific Advice Working Party (SAWP) and the Biostatistics working party (BSWP) at the European Medicines Agency (EMA) and has been a member of the International Council for Harmonisation ICH-E17 working group. |
Discussants:
| |
Nicky Best (GSK) (on behalf of the EFSPI/PSI Historical Data SIG) Nicky Best was an academic statistician for 20 years, starting out at the Medical Research Council Biostatistics Unit in Cambridge, UK before moving to Imperial College London, where she was professor of Statistics and Epidemiology. Her research interests focused around the development and application of Bayesian methods in health and social science, and she is a co-developer of the BUGS Bayesian software package. In 2014 she moved to GlaxoSmithKline (GSK), where she is Head of the Advanced Biostatistics and Data Analytics group. She was awarded the RSS/PSI award for Statistical Excellence in the Pharmaceutical Industry in 2015 for her leading role in implementing expert prior elicitation methods and statistical assurance calculations to improve decision making in clinical development at GSK, and the RSS Bradford Hill Medal in 2018 for her contributions to the exposition and application of Bayesian methods to clinical trials, cost-effectiveness, epidemiology and drug development programmes. |
| |
Lisa LaVange (University of North Carolina, Chapel Hill) Lisa LaVange, PhD, is Professor and Associate Chair of Biostatistics, Gillings School of Global Public Health, UNC-CH. She is also director of the department’s Collaborative Studies Coordinating Center. From 2011 to 2017, Dr. LaVange led the Office of Biostatistics, CDER, FDA, where she directed over 200 statisticians involved in the development and application of statistical methodology for drug regulation. Prior to her government and academic experience, she spent 16 years in non-profit research and 10 years in the pharmaceutical industry. Dr. LaVange is an elected fellow of the American Statistical Association (ASA) and is the 2018 ASA President. |
| Registration | |
| PSI Member | Free |
| Non-member | £20 (plus VAT) |
Time: 15:00 - 17:00 UK time
The paper to be presented appeared earlier this year in Pharmaceutical Statistics (Weber, Hemmings, Koch, 17, 329-341) and is motivated by the opportunities and challenges for using Bayesian methods with informative priors to support drug development and licencing when only a small pool of patients is available, as in the case of rare diseases and paediatric population. With a small study population, meeting the expected level of evidence required for regulatory approval can be challenging. The specific focus of the paper is on the use of data‐based priors in the decision-making process of paediatric extrapolation, and results are presented comparing different frequentist and Bayesian meta-analytic methods for combining adult and paediatric data.
In this webinar, the authors will present their paper, followed by discussion on:
- Scientific rationale for borrowing existing data to make inference about drug effects under different settings: rare diseases, extrapolation and use of historical controls.
- Other methods for combining historical and prospective data beyond standard meta-analytic approaches (e.g., robust MAP priors).
- Ways in which the Bayesian strategy could be supplemented or adapted to enable the independent contribution of the new trial data to be formally quantified and assessed.
We are pleased to announce that the meeting will be chaired by Byron Jones (Novartis)
| |
Kristina Weber (Institute for Biostatistics, Hannover Medical School) Kristina Weber is since 2014 a research associate at the Institute of Biostatistics, Hannover Medical School. Her research interests are in the development of efficient and effective research strategies in limited populations. Her PhD thesis focuses on the application of Bayesian methods in paediatric and rare diseases extrapolation concepts. She has joined Roche in November 2018. |
| |
Rob Hemmings (MHRA) Rob has been with the Licensing Division within MHRA for approaching 19 years, has been a co-opted member of CHMP for 11 years; chair of the EMA’s SAWP for the past 8 years; first chair and then member of the EMA’s BSWP since its inception. |
| |
Armin Koch (Institute for Biostatistics, Hannover Medical School) Professor Armin Koch studied mathematics and chemistry at Heidelberg University, has been a research assistant at the German Centre for the Research on Cancer (DKFZ) between 1984 and 1991. Thereafter he has been an employee at the Institute of Medical Biometry at Heidelberg University until in 1999 when he joined the Federal Institute for Drugs and Medical Devices (BfArM) in Germany. From 2001 to 2008 he was head of the unit „Biostatistics and Experimental Design“. Since 2008 he is Director of the Institute for Biostatistics at Hannover Medical School. Prof. Koch is a member of the Scientific Advice Working Party (SAWP) and the Biostatistics working party (BSWP) at the European Medicines Agency (EMA) and has been a member of the International Council for Harmonisation ICH-E17 working group. |
Discussants:
| |
Nicky Best (GSK) (on behalf of the EFSPI/PSI Historical Data SIG) Nicky Best was an academic statistician for 20 years, starting out at the Medical Research Council Biostatistics Unit in Cambridge, UK before moving to Imperial College London, where she was professor of Statistics and Epidemiology. Her research interests focused around the development and application of Bayesian methods in health and social science, and she is a co-developer of the BUGS Bayesian software package. In 2014 she moved to GlaxoSmithKline (GSK), where she is Head of the Advanced Biostatistics and Data Analytics group. She was awarded the RSS/PSI award for Statistical Excellence in the Pharmaceutical Industry in 2015 for her leading role in implementing expert prior elicitation methods and statistical assurance calculations to improve decision making in clinical development at GSK, and the RSS Bradford Hill Medal in 2018 for her contributions to the exposition and application of Bayesian methods to clinical trials, cost-effectiveness, epidemiology and drug development programmes. |
| |
Lisa LaVange (University of North Carolina, Chapel Hill) Lisa LaVange, PhD, is Professor and Associate Chair of Biostatistics, Gillings School of Global Public Health, UNC-CH. She is also director of the department’s Collaborative Studies Coordinating Center. From 2011 to 2017, Dr. LaVange led the Office of Biostatistics, CDER, FDA, where she directed over 200 statisticians involved in the development and application of statistical methodology for drug regulation. Prior to her government and academic experience, she spent 16 years in non-profit research and 10 years in the pharmaceutical industry. Dr. LaVange is an elected fellow of the American Statistical Association (ASA) and is the 2018 ASA President. |
| Registration | |
| PSI Member | Free |
| Non-member | £20 (plus VAT) |
Time: 15:00 - 17:00 UK time
The paper to be presented appeared earlier this year in Pharmaceutical Statistics (Weber, Hemmings, Koch, 17, 329-341) and is motivated by the opportunities and challenges for using Bayesian methods with informative priors to support drug development and licencing when only a small pool of patients is available, as in the case of rare diseases and paediatric population. With a small study population, meeting the expected level of evidence required for regulatory approval can be challenging. The specific focus of the paper is on the use of data‐based priors in the decision-making process of paediatric extrapolation, and results are presented comparing different frequentist and Bayesian meta-analytic methods for combining adult and paediatric data.
In this webinar, the authors will present their paper, followed by discussion on:
- Scientific rationale for borrowing existing data to make inference about drug effects under different settings: rare diseases, extrapolation and use of historical controls.
- Other methods for combining historical and prospective data beyond standard meta-analytic approaches (e.g., robust MAP priors).
- Ways in which the Bayesian strategy could be supplemented or adapted to enable the independent contribution of the new trial data to be formally quantified and assessed.
We are pleased to announce that the meeting will be chaired by Byron Jones (Novartis)
| |
Kristina Weber (Institute for Biostatistics, Hannover Medical School) Kristina Weber is since 2014 a research associate at the Institute of Biostatistics, Hannover Medical School. Her research interests are in the development of efficient and effective research strategies in limited populations. Her PhD thesis focuses on the application of Bayesian methods in paediatric and rare diseases extrapolation concepts. She has joined Roche in November 2018. |
| |
Rob Hemmings (MHRA) Rob has been with the Licensing Division within MHRA for approaching 19 years, has been a co-opted member of CHMP for 11 years; chair of the EMA’s SAWP for the past 8 years; first chair and then member of the EMA’s BSWP since its inception. |
| |
Armin Koch (Institute for Biostatistics, Hannover Medical School) Professor Armin Koch studied mathematics and chemistry at Heidelberg University, has been a research assistant at the German Centre for the Research on Cancer (DKFZ) between 1984 and 1991. Thereafter he has been an employee at the Institute of Medical Biometry at Heidelberg University until in 1999 when he joined the Federal Institute for Drugs and Medical Devices (BfArM) in Germany. From 2001 to 2008 he was head of the unit „Biostatistics and Experimental Design“. Since 2008 he is Director of the Institute for Biostatistics at Hannover Medical School. Prof. Koch is a member of the Scientific Advice Working Party (SAWP) and the Biostatistics working party (BSWP) at the European Medicines Agency (EMA) and has been a member of the International Council for Harmonisation ICH-E17 working group. |
Discussants:
| |
Nicky Best (GSK) (on behalf of the EFSPI/PSI Historical Data SIG) Nicky Best was an academic statistician for 20 years, starting out at the Medical Research Council Biostatistics Unit in Cambridge, UK before moving to Imperial College London, where she was professor of Statistics and Epidemiology. Her research interests focused around the development and application of Bayesian methods in health and social science, and she is a co-developer of the BUGS Bayesian software package. In 2014 she moved to GlaxoSmithKline (GSK), where she is Head of the Advanced Biostatistics and Data Analytics group. She was awarded the RSS/PSI award for Statistical Excellence in the Pharmaceutical Industry in 2015 for her leading role in implementing expert prior elicitation methods and statistical assurance calculations to improve decision making in clinical development at GSK, and the RSS Bradford Hill Medal in 2018 for her contributions to the exposition and application of Bayesian methods to clinical trials, cost-effectiveness, epidemiology and drug development programmes. |
| |
Lisa LaVange (University of North Carolina, Chapel Hill) Lisa LaVange, PhD, is Professor and Associate Chair of Biostatistics, Gillings School of Global Public Health, UNC-CH. She is also director of the department’s Collaborative Studies Coordinating Center. From 2011 to 2017, Dr. LaVange led the Office of Biostatistics, CDER, FDA, where she directed over 200 statisticians involved in the development and application of statistical methodology for drug regulation. Prior to her government and academic experience, she spent 16 years in non-profit research and 10 years in the pharmaceutical industry. Dr. LaVange is an elected fellow of the American Statistical Association (ASA) and is the 2018 ASA President. |
| Registration | |
| PSI Member | Free |
| Non-member | £20 (plus VAT) |
Time: 15:00 - 17:00 UK time
The paper to be presented appeared earlier this year in Pharmaceutical Statistics (Weber, Hemmings, Koch, 17, 329-341) and is motivated by the opportunities and challenges for using Bayesian methods with informative priors to support drug development and licencing when only a small pool of patients is available, as in the case of rare diseases and paediatric population. With a small study population, meeting the expected level of evidence required for regulatory approval can be challenging. The specific focus of the paper is on the use of data‐based priors in the decision-making process of paediatric extrapolation, and results are presented comparing different frequentist and Bayesian meta-analytic methods for combining adult and paediatric data.
In this webinar, the authors will present their paper, followed by discussion on:
- Scientific rationale for borrowing existing data to make inference about drug effects under different settings: rare diseases, extrapolation and use of historical controls.
- Other methods for combining historical and prospective data beyond standard meta-analytic approaches (e.g., robust MAP priors).
- Ways in which the Bayesian strategy could be supplemented or adapted to enable the independent contribution of the new trial data to be formally quantified and assessed.
We are pleased to announce that the meeting will be chaired by Byron Jones (Novartis)
| |
Kristina Weber (Institute for Biostatistics, Hannover Medical School) Kristina Weber is since 2014 a research associate at the Institute of Biostatistics, Hannover Medical School. Her research interests are in the development of efficient and effective research strategies in limited populations. Her PhD thesis focuses on the application of Bayesian methods in paediatric and rare diseases extrapolation concepts. She has joined Roche in November 2018. |
| |
Rob Hemmings (MHRA) Rob has been with the Licensing Division within MHRA for approaching 19 years, has been a co-opted member of CHMP for 11 years; chair of the EMA’s SAWP for the past 8 years; first chair and then member of the EMA’s BSWP since its inception. |
| |
Armin Koch (Institute for Biostatistics, Hannover Medical School) Professor Armin Koch studied mathematics and chemistry at Heidelberg University, has been a research assistant at the German Centre for the Research on Cancer (DKFZ) between 1984 and 1991. Thereafter he has been an employee at the Institute of Medical Biometry at Heidelberg University until in 1999 when he joined the Federal Institute for Drugs and Medical Devices (BfArM) in Germany. From 2001 to 2008 he was head of the unit „Biostatistics and Experimental Design“. Since 2008 he is Director of the Institute for Biostatistics at Hannover Medical School. Prof. Koch is a member of the Scientific Advice Working Party (SAWP) and the Biostatistics working party (BSWP) at the European Medicines Agency (EMA) and has been a member of the International Council for Harmonisation ICH-E17 working group. |
Discussants:
| |
Nicky Best (GSK) (on behalf of the EFSPI/PSI Historical Data SIG) Nicky Best was an academic statistician for 20 years, starting out at the Medical Research Council Biostatistics Unit in Cambridge, UK before moving to Imperial College London, where she was professor of Statistics and Epidemiology. Her research interests focused around the development and application of Bayesian methods in health and social science, and she is a co-developer of the BUGS Bayesian software package. In 2014 she moved to GlaxoSmithKline (GSK), where she is Head of the Advanced Biostatistics and Data Analytics group. She was awarded the RSS/PSI award for Statistical Excellence in the Pharmaceutical Industry in 2015 for her leading role in implementing expert prior elicitation methods and statistical assurance calculations to improve decision making in clinical development at GSK, and the RSS Bradford Hill Medal in 2018 for her contributions to the exposition and application of Bayesian methods to clinical trials, cost-effectiveness, epidemiology and drug development programmes. |
| |
Lisa LaVange (University of North Carolina, Chapel Hill) Lisa LaVange, PhD, is Professor and Associate Chair of Biostatistics, Gillings School of Global Public Health, UNC-CH. She is also director of the department’s Collaborative Studies Coordinating Center. From 2011 to 2017, Dr. LaVange led the Office of Biostatistics, CDER, FDA, where she directed over 200 statisticians involved in the development and application of statistical methodology for drug regulation. Prior to her government and academic experience, she spent 16 years in non-profit research and 10 years in the pharmaceutical industry. Dr. LaVange is an elected fellow of the American Statistical Association (ASA) and is the 2018 ASA President. |
| Registration | |
| PSI Member | Free |
| Non-member | £20 (plus VAT) |
