The utility of real‐world evidence for benefit‐risk assessment, communication, and evaluation of pharmaceuticals: Case studies

Abstract

In recent years, novel types of real-world evidence (RWE) have played a role in various decision-making processes relating to medicinal products, including regulatory approval, patient access, health technology assessment, safety monitoring, clinical use, and post-approval lifecycle management. We therefore reviewed the potential utility of RWE in the cycle of medicinal product benefit-risk (BR) assessment, communication/risk minimization and evaluation ("BRACE"). Methods: A convenience sample of illustrative studies was drawn from the published literature and examined. Specifically, we examined the purpose for using RWE, the type of RWE used, its novelty and how it might be integrated with other data and activities of the BRACE cycle, and how it contributed to regulatory decision-making. Results: Eight studies were selected with each illustrating a different activity in the BRACE cycle ranging from BR assessment in the preapproval setting, post-approval assessment of safety or effectiveness, communicating BR information to patients and healthcare professionals, and evaluating the effectiveness of risk minimization initiatives to support a positive BR balance. Conclusions: RWE has an important role in informing regulatory decision-making regarding the BR management of medicines. With increasing digitalization, facilitating data collection and stakeholder engagement in health, this role is only expected to expand in the future. To reach the full potential of RWE, both regulators and sponsors will need to be familiar with a range of existing and emerging methods for generating and analyzing such evidence appropriately and achieve convergence regarding how different types of RWE can best be used to inform BR management and decision-making.

Navigating a transforming landscape: the evolving role of pharmacovigilance physicians in drug development and implications for future challenges and training requirements

“…This data comes from sources beyond traditional clinical trials, encompassing registries and other resources ( Cave et al, 2019 ). There is a growing emphasis on leveraging RWE alongside traditional clinical trial data in PV ( Hammad et al, 2008 ; Hammad et al, 2013 ; Margulis et al, 2013 ; Pinheiro et al, 2013 ) and benefit risk assessment ( Pinto et al, 2019 ; Radawski et al, 2020 ). The idea is to harness big data for post-marketing surveillance of rare adverse events as well as to evaluate long-term safety profiles of drugs.…”

Navigating a transforming landscape: the evolving role of pharmacovigilance physicians in drug development and implications for future challenges and training requirements

“…This data comes from sources beyond traditional clinical trials, encompassing registries and other resources ( Cave et al, 2019 ). There is a growing emphasis on leveraging RWE alongside traditional clinical trial data in PV ( Hammad et al, 2008 ; Hammad et al, 2013 ; Margulis et al, 2013 ; Pinheiro et al, 2013 ) and benefit risk assessment ( Pinto et al, 2019 ; Radawski et al, 2020 ). The idea is to harness big data for post-marketing surveillance of rare adverse events as well as to evaluate long-term safety profiles of drugs.…”

Communicating for the Safe Use of Medicines: Progress and Directions for the 2020s Promoted by the Special Interest Group of the International Society of Pharmacovigilance

“…In 2012, the International Society for Pharmacoepidemiology (ISPE), which some refer to as a sister learned society of ISoP, established its SIG on Benefit-Risk Assessment, Communication and Evaluation (BRACE) with the mandate to promote the intersection of pharmacoepidemiology and BRACE activities through methods development and training offers [ 98 ]. The ISPE BRACE SIG has called for multidisciplinary collaborations of pharmacoepidemiologists, patients, and healthcare professionals, and use of real-world data for evidence generation and decision making on risk minimisation [ 99 , 100 ]. Furthermore, some of its members developed the RIMES Statement to improve the reporting quality of studies evaluating risk minimisation and communication interventions [ 101 ].…”

ISPE‐Endorsed Guidance in Using Electronic Health Records for Comparative Effectiveness Research in COVID‐19: Opportunities and Trade‐Offs

“…Databases that reflect routine care delivery include electronic health records (EHRs), administrative health insurance claims, disease and product registries, and other non‐research‐specific data sources (for example, social media). 9 The advantages of RWE providing timely, generalizable evidence from a large, diverse group of patients are well‐recognized, particularly for a public health crisis like the COVID‐19 pandemic. 10 , 11 To capitalize on the RWE offerings to inform the management of COVID‐19, we need access to high‐quality healthcare data, rigorous study designs, and proper implementation of appropriate statistical methods to ensure unbiased and robust results.…”

“…RWE can be generated through a range of applications, like individualized prescribing, postmarketing surveillance, and can support policy or reimbursement decisions. Databases that reflect routine care delivery include electronic health records (EHRs), administrative health insurance claims, disease and product registries, and other non‐research‐specific data sources (for example, social media) 9 . The advantages of RWE providing timely, generalizable evidence from a large, diverse group of patients are well‐recognized, particularly for a public health crisis like the COVID‐19 pandemic 10,11 .…”

Navigating a transforming landscape: the evolving role of pharmacovigilance physicians in drug development and implications for future challenges and training requirements

“…This data comes from sources beyond traditional clinical trials, encompassing registries and other resources ( Cave et al, 2019 ). There is a growing emphasis on leveraging RWE alongside traditional clinical trial data in PV ( Hammad et al, 2008 ; Hammad et al, 2013 ; Margulis et al, 2013 ; Pinheiro et al, 2013 ) and benefit risk assessment ( Pinto et al, 2019 ; Radawski et al, 2020 ). The idea is to harness big data for post-marketing surveillance of rare adverse events as well as to evaluate long-term safety profiles of drugs.…”

Communicating for the Safe Use of Medicines: Progress and Directions for the 2020s Promoted by the Special Interest Group of the International Society of Pharmacovigilance

“…In 2012, the International Society for Pharmacoepidemiology (ISPE), which some refer to as a sister learned society of ISoP, established its SIG on Benefit-Risk Assessment, Communication and Evaluation (BRACE) with the mandate to promote the intersection of pharmacoepidemiology and BRACE activities through methods development and training offers [ 98 ]. The ISPE BRACE SIG has called for multidisciplinary collaborations of pharmacoepidemiologists, patients, and healthcare professionals, and use of real-world data for evidence generation and decision making on risk minimisation [ 99 , 100 ]. Furthermore, some of its members developed the RIMES Statement to improve the reporting quality of studies evaluating risk minimisation and communication interventions [ 101 ].…”

ISPE‐Endorsed Guidance in Using Electronic Health Records for Comparative Effectiveness Research in COVID‐19: Opportunities and Trade‐Offs

“…Databases that reflect routine care delivery include electronic health records (EHRs), administrative health insurance claims, disease and product registries, and other non‐research‐specific data sources (for example, social media). 9 The advantages of RWE providing timely, generalizable evidence from a large, diverse group of patients are well‐recognized, particularly for a public health crisis like the COVID‐19 pandemic. 10 , 11 To capitalize on the RWE offerings to inform the management of COVID‐19, we need access to high‐quality healthcare data, rigorous study designs, and proper implementation of appropriate statistical methods to ensure unbiased and robust results.…”

“…RWE can be generated through a range of applications, like individualized prescribing, postmarketing surveillance, and can support policy or reimbursement decisions. Databases that reflect routine care delivery include electronic health records (EHRs), administrative health insurance claims, disease and product registries, and other non‐research‐specific data sources (for example, social media) 9 . The advantages of RWE providing timely, generalizable evidence from a large, diverse group of patients are well‐recognized, particularly for a public health crisis like the COVID‐19 pandemic 10,11 .…”

Navigating a transforming landscape: the evolving role of pharmacovigilance physicians in drug development and implications for future challenges and training requirements

“…This data comes from sources beyond traditional clinical trials, encompassing registries and other resources ( Cave et al, 2019 ). There is a growing emphasis on leveraging RWE alongside traditional clinical trial data in PV ( Hammad et al, 2008 ; Hammad et al, 2013 ; Margulis et al, 2013 ; Pinheiro et al, 2013 ) and benefit risk assessment ( Pinto et al, 2019 ; Radawski et al, 2020 ). The idea is to harness big data for post-marketing surveillance of rare adverse events as well as to evaluate long-term safety profiles of drugs.…”

Communicating for the Safe Use of Medicines: Progress and Directions for the 2020s Promoted by the Special Interest Group of the International Society of Pharmacovigilance

“…In 2012, the International Society for Pharmacoepidemiology (ISPE), which some refer to as a sister learned society of ISoP, established its SIG on Benefit-Risk Assessment, Communication and Evaluation (BRACE) with the mandate to promote the intersection of pharmacoepidemiology and BRACE activities through methods development and training offers [ 98 ]. The ISPE BRACE SIG has called for multidisciplinary collaborations of pharmacoepidemiologists, patients, and healthcare professionals, and use of real-world data for evidence generation and decision making on risk minimisation [ 99 , 100 ]. Furthermore, some of its members developed the RIMES Statement to improve the reporting quality of studies evaluating risk minimisation and communication interventions [ 101 ].…”

ISPE‐Endorsed Guidance in Using Electronic Health Records for Comparative Effectiveness Research in COVID‐19: Opportunities and Trade‐Offs

“…Databases that reflect routine care delivery include electronic health records (EHRs), administrative health insurance claims, disease and product registries, and other non‐research‐specific data sources (for example, social media). 9 The advantages of RWE providing timely, generalizable evidence from a large, diverse group of patients are well‐recognized, particularly for a public health crisis like the COVID‐19 pandemic. 10 , 11 To capitalize on the RWE offerings to inform the management of COVID‐19, we need access to high‐quality healthcare data, rigorous study designs, and proper implementation of appropriate statistical methods to ensure unbiased and robust results.…”

“…RWE can be generated through a range of applications, like individualized prescribing, postmarketing surveillance, and can support policy or reimbursement decisions. Databases that reflect routine care delivery include electronic health records (EHRs), administrative health insurance claims, disease and product registries, and other non‐research‐specific data sources (for example, social media) 9 . The advantages of RWE providing timely, generalizable evidence from a large, diverse group of patients are well‐recognized, particularly for a public health crisis like the COVID‐19 pandemic 10,11 .…”