PSI Scientific Committee Webinar: Heart Failure Trials: Novel Estimands and Methodologies to Evaluate Therapies based on the Totality of Evidence
Heart failure (HF) is a common and global health problem affecting approx. 2% of adults in developed countries. Good news is that with new treatments on the market, HF has been converted from a short-term and quickly fatal condition to a chronic disease, which is characterized by recurrent non-fatal events (HF hospitalizations) and relatively low disease-related mortality. Classical heart failure trials have used a composite primary endpoint of cardiovascular (CV) death and HF hospitalization. This endpoint was then analyzed using a ‘time to first composite event’ analysis.
Various limitations of this endpoint have been raised in recent years. Among others, the ‘time to first composite event’ endpoint is thought to not fully capture the disease burden as it ignores all events that occur after the first event. Given that a number of recent large HF
outcome trials have failed to show a clinical benefit for patients using the traditional endpoint, clinical teams are reviewing novel endpoints that better capture clinical benefit and which
adapt to the changing disease profile.
In this session, we will discuss some of the recently proposed estimands and their associated analysis methods, ranging from composite endpoints of recurrent HF hospitalizations (HFH) and death to joint frailty models for recurrent HFH and death. We will illustrate these approaches based on various case-studies and discuss benefits as well as limitations from an academic, regulatory and industry perspective.
Application of Recurrent Events Methodology in Cardiovascular Trials
Dr. Brian Claggett (Harvard Medical School)
We describe a range of alternative models for recurrent events data collected in cardiovascular trials. We consider their applicability and interpretation from a medical context and illustrate them using data from a particular trial.
The Totality of Evidence: Is More the Same as Better?
Dr. Bruce Binkowitz (Merck)
Analysis of time to first event is a long held tradition for trials in the cardiovascular area, including heart failure. Yet subjects in these studies can experience more than 1 event. Recent literature has focused on utilizing all events experienced by each subject as a way of increasing efficiency through having to enroll less subjects, use less investigator sites, and save money. Consideration for examining all events further extends to measuring total patient burden, cost effectiveness, and most importantly, capturing the best picture of a subject's condition and therefore the best potential therapy. This presentation will discuss how analyzing total events isn't as simple as designing a traditional time to first event study and, for example, running an Anderson-Gill extension to a Cox PH model on all events. Examples will be taken from actual trials including a trial examining subjects with acute decompensated heart failure.
Recurrent or Multiple Event Analyses in Cardiovascular Trials
Dr. H.M. James Hung, US FDA
In cardiovascular or renal trials that we have seen in regulatory applications, major adverse clinical events are almost always assessed using analysis of time to first occurrence of the events. As some component events occur much more frequently, such as hospitalizations, during the trial, the analysis that includes all the events may improve statistical efficiency and capture disease burden of patients more properly. In this talk, I shall share a number of regulatory experiences with recurrent or multiple event analyses to give my insights into the possible values of such analysis and to stipulate the issues that need more attention.
Registration fee: None
This webinar is free of charge. However, attendees must register on the PSI website in order to obtain the dial-in details and the webinar link.
We do encourage your participation. If you have questions relating to this webinar, or any of the listed talks, ahead of the webinar, please email them to Mouna.Akacha@novartis.com
We will do our best to discuss them at the webinar.
PSI Scientific Committee Webinar: Heart Failure Trials: Novel Estimands and Methodologies to Evaluate Therapies based on the Totality of Evidence
Heart failure (HF) is a common and global health problem affecting approx. 2% of adults in developed countries. Good news is that with new treatments on the market, HF has been converted from a short-term and quickly fatal condition to a chronic disease, which is characterized by recurrent non-fatal events (HF hospitalizations) and relatively low disease-related mortality. Classical heart failure trials have used a composite primary endpoint of cardiovascular (CV) death and HF hospitalization. This endpoint was then analyzed using a ‘time to first composite event’ analysis.
Various limitations of this endpoint have been raised in recent years. Among others, the ‘time to first composite event’ endpoint is thought to not fully capture the disease burden as it ignores all events that occur after the first event. Given that a number of recent large HF
outcome trials have failed to show a clinical benefit for patients using the traditional endpoint, clinical teams are reviewing novel endpoints that better capture clinical benefit and which
adapt to the changing disease profile.
In this session, we will discuss some of the recently proposed estimands and their associated analysis methods, ranging from composite endpoints of recurrent HF hospitalizations (HFH) and death to joint frailty models for recurrent HFH and death. We will illustrate these approaches based on various case-studies and discuss benefits as well as limitations from an academic, regulatory and industry perspective.
Application of Recurrent Events Methodology in Cardiovascular Trials
Dr. Brian Claggett (Harvard Medical School)
We describe a range of alternative models for recurrent events data collected in cardiovascular trials. We consider their applicability and interpretation from a medical context and illustrate them using data from a particular trial.
The Totality of Evidence: Is More the Same as Better?
Dr. Bruce Binkowitz (Merck)
Analysis of time to first event is a long held tradition for trials in the cardiovascular area, including heart failure. Yet subjects in these studies can experience more than 1 event. Recent literature has focused on utilizing all events experienced by each subject as a way of increasing efficiency through having to enroll less subjects, use less investigator sites, and save money. Consideration for examining all events further extends to measuring total patient burden, cost effectiveness, and most importantly, capturing the best picture of a subject's condition and therefore the best potential therapy. This presentation will discuss how analyzing total events isn't as simple as designing a traditional time to first event study and, for example, running an Anderson-Gill extension to a Cox PH model on all events. Examples will be taken from actual trials including a trial examining subjects with acute decompensated heart failure.
Recurrent or Multiple Event Analyses in Cardiovascular Trials
Dr. H.M. James Hung, US FDA
In cardiovascular or renal trials that we have seen in regulatory applications, major adverse clinical events are almost always assessed using analysis of time to first occurrence of the events. As some component events occur much more frequently, such as hospitalizations, during the trial, the analysis that includes all the events may improve statistical efficiency and capture disease burden of patients more properly. In this talk, I shall share a number of regulatory experiences with recurrent or multiple event analyses to give my insights into the possible values of such analysis and to stipulate the issues that need more attention.
Registration fee: None
This webinar is free of charge. However, attendees must register on the PSI website in order to obtain the dial-in details and the webinar link.
We do encourage your participation. If you have questions relating to this webinar, or any of the listed talks, ahead of the webinar, please email them to Mouna.Akacha@novartis.com
We will do our best to discuss them at the webinar.
PSI Scientific Committee Webinar: Heart Failure Trials: Novel Estimands and Methodologies to Evaluate Therapies based on the Totality of Evidence
Heart failure (HF) is a common and global health problem affecting approx. 2% of adults in developed countries. Good news is that with new treatments on the market, HF has been converted from a short-term and quickly fatal condition to a chronic disease, which is characterized by recurrent non-fatal events (HF hospitalizations) and relatively low disease-related mortality. Classical heart failure trials have used a composite primary endpoint of cardiovascular (CV) death and HF hospitalization. This endpoint was then analyzed using a ‘time to first composite event’ analysis.
Various limitations of this endpoint have been raised in recent years. Among others, the ‘time to first composite event’ endpoint is thought to not fully capture the disease burden as it ignores all events that occur after the first event. Given that a number of recent large HF
outcome trials have failed to show a clinical benefit for patients using the traditional endpoint, clinical teams are reviewing novel endpoints that better capture clinical benefit and which
adapt to the changing disease profile.
In this session, we will discuss some of the recently proposed estimands and their associated analysis methods, ranging from composite endpoints of recurrent HF hospitalizations (HFH) and death to joint frailty models for recurrent HFH and death. We will illustrate these approaches based on various case-studies and discuss benefits as well as limitations from an academic, regulatory and industry perspective.
Application of Recurrent Events Methodology in Cardiovascular Trials
Dr. Brian Claggett (Harvard Medical School)
We describe a range of alternative models for recurrent events data collected in cardiovascular trials. We consider their applicability and interpretation from a medical context and illustrate them using data from a particular trial.
The Totality of Evidence: Is More the Same as Better?
Dr. Bruce Binkowitz (Merck)
Analysis of time to first event is a long held tradition for trials in the cardiovascular area, including heart failure. Yet subjects in these studies can experience more than 1 event. Recent literature has focused on utilizing all events experienced by each subject as a way of increasing efficiency through having to enroll less subjects, use less investigator sites, and save money. Consideration for examining all events further extends to measuring total patient burden, cost effectiveness, and most importantly, capturing the best picture of a subject's condition and therefore the best potential therapy. This presentation will discuss how analyzing total events isn't as simple as designing a traditional time to first event study and, for example, running an Anderson-Gill extension to a Cox PH model on all events. Examples will be taken from actual trials including a trial examining subjects with acute decompensated heart failure.
Recurrent or Multiple Event Analyses in Cardiovascular Trials
Dr. H.M. James Hung, US FDA
In cardiovascular or renal trials that we have seen in regulatory applications, major adverse clinical events are almost always assessed using analysis of time to first occurrence of the events. As some component events occur much more frequently, such as hospitalizations, during the trial, the analysis that includes all the events may improve statistical efficiency and capture disease burden of patients more properly. In this talk, I shall share a number of regulatory experiences with recurrent or multiple event analyses to give my insights into the possible values of such analysis and to stipulate the issues that need more attention.
Registration fee: None
This webinar is free of charge. However, attendees must register on the PSI website in order to obtain the dial-in details and the webinar link.
We do encourage your participation. If you have questions relating to this webinar, or any of the listed talks, ahead of the webinar, please email them to Mouna.Akacha@novartis.com
We will do our best to discuss them at the webinar.
PSI Scientific Committee Webinar: Heart Failure Trials: Novel Estimands and Methodologies to Evaluate Therapies based on the Totality of Evidence
Heart failure (HF) is a common and global health problem affecting approx. 2% of adults in developed countries. Good news is that with new treatments on the market, HF has been converted from a short-term and quickly fatal condition to a chronic disease, which is characterized by recurrent non-fatal events (HF hospitalizations) and relatively low disease-related mortality. Classical heart failure trials have used a composite primary endpoint of cardiovascular (CV) death and HF hospitalization. This endpoint was then analyzed using a ‘time to first composite event’ analysis.
Various limitations of this endpoint have been raised in recent years. Among others, the ‘time to first composite event’ endpoint is thought to not fully capture the disease burden as it ignores all events that occur after the first event. Given that a number of recent large HF
outcome trials have failed to show a clinical benefit for patients using the traditional endpoint, clinical teams are reviewing novel endpoints that better capture clinical benefit and which
adapt to the changing disease profile.
In this session, we will discuss some of the recently proposed estimands and their associated analysis methods, ranging from composite endpoints of recurrent HF hospitalizations (HFH) and death to joint frailty models for recurrent HFH and death. We will illustrate these approaches based on various case-studies and discuss benefits as well as limitations from an academic, regulatory and industry perspective.
Application of Recurrent Events Methodology in Cardiovascular Trials
Dr. Brian Claggett (Harvard Medical School)
We describe a range of alternative models for recurrent events data collected in cardiovascular trials. We consider their applicability and interpretation from a medical context and illustrate them using data from a particular trial.
The Totality of Evidence: Is More the Same as Better?
Dr. Bruce Binkowitz (Merck)
Analysis of time to first event is a long held tradition for trials in the cardiovascular area, including heart failure. Yet subjects in these studies can experience more than 1 event. Recent literature has focused on utilizing all events experienced by each subject as a way of increasing efficiency through having to enroll less subjects, use less investigator sites, and save money. Consideration for examining all events further extends to measuring total patient burden, cost effectiveness, and most importantly, capturing the best picture of a subject's condition and therefore the best potential therapy. This presentation will discuss how analyzing total events isn't as simple as designing a traditional time to first event study and, for example, running an Anderson-Gill extension to a Cox PH model on all events. Examples will be taken from actual trials including a trial examining subjects with acute decompensated heart failure.
Recurrent or Multiple Event Analyses in Cardiovascular Trials
Dr. H.M. James Hung, US FDA
In cardiovascular or renal trials that we have seen in regulatory applications, major adverse clinical events are almost always assessed using analysis of time to first occurrence of the events. As some component events occur much more frequently, such as hospitalizations, during the trial, the analysis that includes all the events may improve statistical efficiency and capture disease burden of patients more properly. In this talk, I shall share a number of regulatory experiences with recurrent or multiple event analyses to give my insights into the possible values of such analysis and to stipulate the issues that need more attention.
Registration fee: None
This webinar is free of charge. However, attendees must register on the PSI website in order to obtain the dial-in details and the webinar link.
We do encourage your participation. If you have questions relating to this webinar, or any of the listed talks, ahead of the webinar, please email them to Mouna.Akacha@novartis.com
We will do our best to discuss them at the webinar.
PSI Scientific Committee Webinar: Heart Failure Trials: Novel Estimands and Methodologies to Evaluate Therapies based on the Totality of Evidence
Heart failure (HF) is a common and global health problem affecting approx. 2% of adults in developed countries. Good news is that with new treatments on the market, HF has been converted from a short-term and quickly fatal condition to a chronic disease, which is characterized by recurrent non-fatal events (HF hospitalizations) and relatively low disease-related mortality. Classical heart failure trials have used a composite primary endpoint of cardiovascular (CV) death and HF hospitalization. This endpoint was then analyzed using a ‘time to first composite event’ analysis.
Various limitations of this endpoint have been raised in recent years. Among others, the ‘time to first composite event’ endpoint is thought to not fully capture the disease burden as it ignores all events that occur after the first event. Given that a number of recent large HF
outcome trials have failed to show a clinical benefit for patients using the traditional endpoint, clinical teams are reviewing novel endpoints that better capture clinical benefit and which
adapt to the changing disease profile.
In this session, we will discuss some of the recently proposed estimands and their associated analysis methods, ranging from composite endpoints of recurrent HF hospitalizations (HFH) and death to joint frailty models for recurrent HFH and death. We will illustrate these approaches based on various case-studies and discuss benefits as well as limitations from an academic, regulatory and industry perspective.
Application of Recurrent Events Methodology in Cardiovascular Trials
Dr. Brian Claggett (Harvard Medical School)
We describe a range of alternative models for recurrent events data collected in cardiovascular trials. We consider their applicability and interpretation from a medical context and illustrate them using data from a particular trial.
The Totality of Evidence: Is More the Same as Better?
Dr. Bruce Binkowitz (Merck)
Analysis of time to first event is a long held tradition for trials in the cardiovascular area, including heart failure. Yet subjects in these studies can experience more than 1 event. Recent literature has focused on utilizing all events experienced by each subject as a way of increasing efficiency through having to enroll less subjects, use less investigator sites, and save money. Consideration for examining all events further extends to measuring total patient burden, cost effectiveness, and most importantly, capturing the best picture of a subject's condition and therefore the best potential therapy. This presentation will discuss how analyzing total events isn't as simple as designing a traditional time to first event study and, for example, running an Anderson-Gill extension to a Cox PH model on all events. Examples will be taken from actual trials including a trial examining subjects with acute decompensated heart failure.
Recurrent or Multiple Event Analyses in Cardiovascular Trials
Dr. H.M. James Hung, US FDA
In cardiovascular or renal trials that we have seen in regulatory applications, major adverse clinical events are almost always assessed using analysis of time to first occurrence of the events. As some component events occur much more frequently, such as hospitalizations, during the trial, the analysis that includes all the events may improve statistical efficiency and capture disease burden of patients more properly. In this talk, I shall share a number of regulatory experiences with recurrent or multiple event analyses to give my insights into the possible values of such analysis and to stipulate the issues that need more attention.
Registration fee: None
This webinar is free of charge. However, attendees must register on the PSI website in order to obtain the dial-in details and the webinar link.
We do encourage your participation. If you have questions relating to this webinar, or any of the listed talks, ahead of the webinar, please email them to Mouna.Akacha@novartis.com
We will do our best to discuss them at the webinar.
PSI Scientific Committee Webinar: Heart Failure Trials: Novel Estimands and Methodologies to Evaluate Therapies based on the Totality of Evidence
Heart failure (HF) is a common and global health problem affecting approx. 2% of adults in developed countries. Good news is that with new treatments on the market, HF has been converted from a short-term and quickly fatal condition to a chronic disease, which is characterized by recurrent non-fatal events (HF hospitalizations) and relatively low disease-related mortality. Classical heart failure trials have used a composite primary endpoint of cardiovascular (CV) death and HF hospitalization. This endpoint was then analyzed using a ‘time to first composite event’ analysis.
Various limitations of this endpoint have been raised in recent years. Among others, the ‘time to first composite event’ endpoint is thought to not fully capture the disease burden as it ignores all events that occur after the first event. Given that a number of recent large HF
outcome trials have failed to show a clinical benefit for patients using the traditional endpoint, clinical teams are reviewing novel endpoints that better capture clinical benefit and which
adapt to the changing disease profile.
In this session, we will discuss some of the recently proposed estimands and their associated analysis methods, ranging from composite endpoints of recurrent HF hospitalizations (HFH) and death to joint frailty models for recurrent HFH and death. We will illustrate these approaches based on various case-studies and discuss benefits as well as limitations from an academic, regulatory and industry perspective.
Application of Recurrent Events Methodology in Cardiovascular Trials
Dr. Brian Claggett (Harvard Medical School)
We describe a range of alternative models for recurrent events data collected in cardiovascular trials. We consider their applicability and interpretation from a medical context and illustrate them using data from a particular trial.
The Totality of Evidence: Is More the Same as Better?
Dr. Bruce Binkowitz (Merck)
Analysis of time to first event is a long held tradition for trials in the cardiovascular area, including heart failure. Yet subjects in these studies can experience more than 1 event. Recent literature has focused on utilizing all events experienced by each subject as a way of increasing efficiency through having to enroll less subjects, use less investigator sites, and save money. Consideration for examining all events further extends to measuring total patient burden, cost effectiveness, and most importantly, capturing the best picture of a subject's condition and therefore the best potential therapy. This presentation will discuss how analyzing total events isn't as simple as designing a traditional time to first event study and, for example, running an Anderson-Gill extension to a Cox PH model on all events. Examples will be taken from actual trials including a trial examining subjects with acute decompensated heart failure.
Recurrent or Multiple Event Analyses in Cardiovascular Trials
Dr. H.M. James Hung, US FDA
In cardiovascular or renal trials that we have seen in regulatory applications, major adverse clinical events are almost always assessed using analysis of time to first occurrence of the events. As some component events occur much more frequently, such as hospitalizations, during the trial, the analysis that includes all the events may improve statistical efficiency and capture disease burden of patients more properly. In this talk, I shall share a number of regulatory experiences with recurrent or multiple event analyses to give my insights into the possible values of such analysis and to stipulate the issues that need more attention.
Registration fee: None
This webinar is free of charge. However, attendees must register on the PSI website in order to obtain the dial-in details and the webinar link.
We do encourage your participation. If you have questions relating to this webinar, or any of the listed talks, ahead of the webinar, please email them to Mouna.Akacha@novartis.com
We will do our best to discuss them at the webinar.
Upcoming Events
Joint PSI/EFSPI Visualisation SIG 'Wonderful Wednesday' Webinars
Our monthly webinar explores examples of innovative data visualisations relevant to our day to day work. Each month a new dataset is provided from a clinical trial or other relevant example, and participants are invited to submit a graphic that communicates interesting and relevant characteristics of the data.
The event will open with an overview on drug development in women’s health from a clinician perspective. This talk is followed by talks about statistical challenges when planning IVF studies and analysing the menstrual cycles.
This webinar will provide an overview of surrogacy for licensing and reimbursement. In turn, the need of extensions of the SPIRIT and CONSORT statement will be defined and outlined, with case studies to support.
Joint PSI/EFSPI Pre-Clinical SIG Webinar: Virtual Control Groups in Toxicity Studies
Lea Vaas will present how replacement of concurrent control animals by Virtual Control Groups (VCGs) in systemic toxicity studies may help in contributing to the 3R's principle of animal experimentation: Reduce, Refine, Replace.
Joint PSI/EFSPI Data Science SIG Webinar: Developing Digital Measures (Digital Biomarkers) in Drug Development – insights from Mobilise D consortium
We will share a brief overview of what Mobilise D is and why it is an important step stone in the development of digital biomarkers, and how Mobilise D outputs can be relevant for you.
This networking event is aimed at statisticians that are new to the pharmaceutical industry who wish to meet colleagues from different companies and backgrounds.
PSI Webinar: Development of Gene Therapies: Strategic, Scientific, Regulatory and Access Considerations
This webinar will cover the history of cell/gene therapy, major regulatory advances, the role of quantitative scientists in drug development of these novel therapeutics, and discuss opportunities for innovation and product advancement.
This networking event is aimed at statisticians that are new to the pharmaceutical industry who wish to meet colleagues from different companies and backgrounds.
PSI Introduction to Industry Training (ITIT) Course - 2024/2025
An introductory course giving an overview of the pharmaceutical industry and the drug development process as a whole, aimed at those with 1-3 years' experience. It comprises of six 2-day sessions covering a range of topics including Research and Development, Toxicology, Data Management and the Role of a CRO, Clinical Trials, Reimbursement, and Marketing.
This networking event is aimed at statisticians that are new to the pharmaceutical industry who wish to meet colleagues from different companies and backgrounds.
Statisticians in the Pharmaceutical Industry Executive Office: c/o MCI UK Ltd | Unit 24/22 South | Building 4000 | Langstone Park| Langstone Road | Havant | PO9 1SA | UK