This report takes an in-depth look at risk detection, analysis, and mitigation for novel and marketed medicinal products. It investigates the way in which drug risk management has changed over time and provides case studies of drugs that have been pivotal in changing regulations. The future outlook from the perspective of different stakeholders also presented.
FEATURES AND BENEFITS
- Evaluate the ways in which drug safety regulation has evolved and why.
- Assess areas of contention or change in current drug safety regulation in the EU and US.
- Identify key consortia that are working to establish improved methods of predicting drug safety in preclinical development.
- Evaluate the future of drug safety and REMS from the perspective of different stakeholders in the system.
- Understand who is responsible for ensuring the safety of drugs at different parts of the lifecycle.
Current regulatory guidance outlines methods for planning risk communication and minimization strategies that might be imposed in cases where drugs have important benefits but are also associated with risks for patients. This represents an evolution brought about by advances in science and technology.
Risk evaluation and mitigation strategies (REMS) imposed by the FDA have been the subject of criticism since their introduction in 2007. The FDA are listening to stakeholders and current form of REMS is likely to change.
A wealth of research is ongoing within the pharma industry and academia to understand the potential risks associated with a new drug before it reaches the marketplace. A great deal of the work being undertaken focuses on preclinical, predictive models of drug safety and consortia are particularly important in this area.
YOUR KEY QUESTIONS ANSWERED
- What are the different activities required to investigate and manage drug safety?
- What are companies and regulators doing to improve their ability to develop and approve safe drugs?
- Are current regulations likely to change and why?
- What are companies and regulators doing to improve their ability to safeguard public health by minimizing the risks posed by marketed drugs?
- How are other stakeholders influencing the situation?
Table of Contents
- Evolution of risk management practices
- Strategies for risk management imposed by EU and US regulators
- Pre-marketing strategies for detecting risk
- Post-marketing strategies for minimizing risk
- Future outlook: stakeholder perspectives
About the authors
- Detecting risks
- Analysis and evaluation of risk
- Management of risk, including risk communication
- Report outline
Evolution of risk management practices
- Evolution of risk management strategies
- Communication to manage and minimize risk
- Case study: cisapride (Propulsid; Ortho-McNeil-Janssen)
- Case study: alosetron (Lotronex; GlaxoSmithKline)
- Beyond risk communication
- Case study: clozapine (Clozaril; Novartis)
- Case study: thalidomide (Thalomid; Celgene)
- Case study: isotretinoin (Accutane; Roche)
Strategies for risk management imposed by EU and US regulators
- Risk management activities required by the FDA
- Enforcing post-marketing commitments
- Risk Evaluation and Mitigation Strategies
- Medication guides
- Class-wide REMS
- Review of the REMS system
- Risk management activities imposed by the EMA
- Changes to the EU's pharmacovigilance system
- Comparison of risk management activities in the US and the EU
Pre-marketing strategies for detecting risk
- Innovation in preclinical toxicity testing
- In silico screening and chemoinformatics
- In vitro testing
- Animal studies
- Biomarkers in drug development
- Innovation in early clinical drug development
- Exploratory studies: Phase 0
- Monitoring safety during clinical development
- Reporting serious adverse events
- Reporting requirements
- Data mining during drug development
Post-marketing strategies for minimizing risk
- Pharmacovigilance and data mining
- Post-approval clinical research: Phase IV
- Observational pharmacoepidemiological studies
- Descriptive studies
- Targeted clinical investigations
- Risk minimization activities
- Innovation in risk minimization tool design
- Evaluating risk mitigation strategies
Future outlook: stakeholder perspectives
- Pharmaceutical companies
- Lifecycle management
- Implementing organizational change
- Communicating with regulators
- Patients, physicians and pharmacists
- Stakeholder involvement
- Communicating risk
- Informatics and social media
- Research methodology