For companies looking to develop new therapies or improve existing ones, and for the regulators overseeing them, striking right balance between potential benefits to patients and an appropriate level of risk is critical. The drive to innovate, develop new and better products, and help patients live healthier lives has led to numerous medical breakthroughs. But it is just as imperative that products are as safe as possible, and that where there are associated risks, they are identified and deemed acceptable.
Understanding the principles of risk management is crucial in the regulatory world. And while the concept of balancing benefit and risk may be straightforward, in practice, risk management is not only complex but also rapidly changing as it is subject to constant and continuous advances in medicine and technology. William Sietsema, PhD; and J. Michael Sprafka, MS, MPH, PhD, are experts in this area and co-editors of RAPS’ second edition of Risk Management Principles for Devices and Pharmaceuticals: Global Perspectives on Medicinal Product Benefit-Risk Assessment, and they took some time recently to answer a few questions about risk management, the latest developments and the new book.
What core risk management concepts should all regulatory professionals know? Why are they important?
William Sietsema: Core risk management concepts include how to identify potential risks, how to develop a system for continued assessment of risks, and how to develop a plan for risk mitigation, including pre-defined action points. These are important to protect the public health and maintain confidence in a product.
In general, are pharmaceutical and medical device companies today willing to accept more risk in the name of innovation than they have been in the past?
WS: I don’t think the level of risk accepted by pharmaceutical and medical device companies has changed but regulators globally have been more willing to accept risk, particularly for under-treated diseases with serious consequences.
J. Michael Sprafka: In addition, companies have better access to tools to address risk, and these tools are becoming incorporated into the submission and approval process.
Have attitudes among patients and healthcare providers about how much risk is acceptable changed over time?
WS: I think many patients and healthcare providers have always been willing to take more risks than regulators would allow, evidenced by the emphasis on “right to try” legislation. I don’t think this has changed.
Do advances in risk management knowledge and tools allow for greater risks to be taken or do they shrink the risk that must be taken to achieve positive outcomes?
WS: Advances in risk management knowledge and tools allow for awareness of risks but I don’t think they change the risks that patients or caregivers are willing to take.
JMS: The tools allow for greater perspective on suspected and established risks.
The book examines risk as applied in several different national or regional regulatory systems, including the US, EU, Canada and Japan. How is risk handled differently by different regulators? What are the common threads?
WS: Due to the International Council on Harmonisation (ICH), there are more commonalities than differences in each of these regions. Most of the differences between regions are procedural in nature. All regions expect good science to form the foundation for risk management.
Are risk management principles applied differently to medicinal products than other areas where one might need to balance benefit and risk?
WS: Risk management principles are similar in the pharmaceutical and medical device industries to what is observed in other industries, but the types of risks, methods of detection and methods of mitigation may be much different than in other industries.
In the ‘Looking Into the Crystal Ball’ chapter of the book's first edition, which of the author’s predictions were right on and which have yet to materialize?
JMS: Electronic health records (i.e., big data, SENTINEL) have been useful as a postmarketing tool to investigate and evaluate known and suspected risks, but the use of these systems to conduct clinical trials or promote faster adoption of beneficial health services and practices is in its infancy.
What does the future hold for risk management? Are there any predictions in this edition that you think are especially interesting or merit particular attention?
WS: Risk management is a relatively young discipline and is evolving rapidly. Our ability to detect and mitigate risks will improve as new tools and algorithms are made available, and as the industry gains more experience identifying the methods of mitigation that work well and those that don't.
Several chapters highlight a prediction that regulators will continue to focus on the balance between risk and benefit, thus for serious diseases, regulators will continue to accept more risk when considering a product for approval. It also predicts that regulators will monitor safety more closely during a product’s lifecycle. Additional chapters suggest that going forward, regulators will place more structure around their risk-benefit assessments and will innovate their platforms for assessing risk and benefit.
Regulators will also improve their methods of communicating risks to patients and caregivers so that informed decisions can be made. Finally, as the field of risk management progresses, pharmaceutical and device companies will refine their methods for collection and analysis of adverse events data, particularly mining electronic data records for information not previously analyzed.