Around the Globe

Drug Risk Management in China:
Key Considerations from Healthcare Professionals
Sophia Duan
PPC, China

or the first time, Chinese hepatology experts, cardiology experts, and chief pharmacists came together to jointly discuss pharmacovigilance practice and promote the concept of risk management that ensures patient safety throughout the therapeutic product lifecycle at our DIA 2019 China Annual Meeting.

Spurred by ongoing regulatory reforms, routine medical practice has been prioritizing pharmacovigilance as part of its processes for the ethical research, diagnosis and review, and treatment of disease, paying special attention to adverse events that have led to patient injury (e.g., Drug-Induced Liver Injury [DILI] and cardiovascular toxicities) in China. This is the opportunity for healthcare professionals to share information about how ethical review should be strengthened during clinical trials, how to prevent DILI and immune checkpoint inhibitor-associated cardiovascular toxicities, and how to enhance awareness of the importance of pharmacovigilance (PV) from healthcare professionals (HCPs) to industry and regulatory professionals throughout China’s healthcare system.

Key Takeaways

  • The concept of risk management throughout the product lifecycle, from pre-market through post-market, is now widely accepted by industry and regulators alike in China.
  • DILI is often the cause of product disapproval or market withdrawal; it is necessary to identify accurate predictive biomarkers of DILI and effective diagnostic tools for earlier prediction and prevention of DILI.

Pharmaceutical companies in China have already begun to establish basic PV systems. But in addition to industry and regulatory professionals, physicians (especially cardiology experts) are now discussing how to prioritize patient safety in drug development and clinical practice. Speakers participating from several famous national hospitals focused on patient safety in three areas:

Strengthening Ethical Review

Participating in a clinical trial puts every patient at some level of clinical risk. It is now widely recognized that ethics committee review of a clinical trial should consider the rights, safety, and well-being of patients in the study as more important than the interests of science and society. Patient safety in clinical trials can be improved in many practical ways, including better definition and communication of what Serious Adverse Events (SAEs) or Serious Adverse Reaction (SARs) are; better instruction in the study protocol about how to collect SAEs or SARs; and more transparent and genuine communication of risk in unethical “Seeding Trials” (marketing designed to target specific products to selected consumers).

DILI in Drug Development and Post-Approval Safety

A leading cause of acute liver failure in the US, DILI is often the reason a new drug is not approved for the market or the reason an approved drug is withdrawn from the market. Idiosyncratic DILI is more common than intrinsic DILI but is often unpredictable. As a result, it is urgent to advance our understanding of the pathogenesis of, and identify specific predictive biomarkers for, DILI. Working on updating Roussel Uclaf Causality Assessment Method (RUCAM) for causality assessment of DILI represents a good start. Developing objective and standardized DILI diagnostic tools, establishing and maintaining local DILI databases in conjunction with utilizing international databases, and improved monitoring and reporting of DILI, are promising paths to ensuring better patient safety.

Immune Checkpoint Inhibitor-Associated Cardiovascular Toxicities

Immune Checkpoint Inhibitors (ICIs)-associated cardiovascular toxicities have been reported in case series studies. However, because of difficulties in diagnosis and non-specific clinical manifestations, it is widely believed that these toxicities are underreported. Incidence of ICI-associated myocarditis, which typically occurs with an elevated troponin in immunotherapy, has been reported to range from 0.06 to 1 percent of patients prescribed an ICI. High-dose steroids are commonly used for treatment. Joint discussions and decisions by oncology and cardiology experts are essential for effective recognition and treatment of ICI-associated myocarditis to ensure the safety of these patients.