Look behind the lecture: the current and future states of patient-centered pharmacovigilance
In this interview, Brian Edwards, (NDA Regulatory Science Ltd; Surrey, UK), discusses his presentation from DIA 2019 (23—27 June, CA, USA) on the importance of accurate and precise pharmacovigilance and how patient engagement may contribute to the future improvement of this.
Please can you introduce yourself and your institution?
I am a Principal Consultant in pharmacovigilance and drug safety with NDA Regulatory Science Ltd (Surrey, UK). I am also a Board Member of the International Society of Pharmacovigilance (ISoP; London, UK) and Chair of the Pharmaceutical Human Factors and Ergonomics Group (Chartered Institute of Ergonomics and Human Factors, Birmingham, UK).
What is the importance of accurate pharmacovigilance and unique product traceability, especially in reference to biosimilars and biological products?
It is critically important to precisely and accurately identify medicinal products – particularly biological medicines – as they travel through the system. This is to enable us to establish causality of suspected adverse drug reactions – so that we can perform signal detection – and establish real-world effectiveness of individual products. Accurate pharmacovigilance is also very important for performing product recall if there are serious quality issues associated with a product and to enable us to monitor the impact of interchangeability should there be switching of patients between the originator biological and a biosimilar product.
"...we do not have joined leadership to ensure that we have a common approach to managing the pharmacovigilance of products across both systems."
Patient data has quite clearly shown that, for patients with autoimmune diseases – such as rheumatoid arthritis – their journeys are very complicated; these patients often switch between using different biological drug products and biosimilars. Therefore, it is critical that we can identify and monitor each individual, biological product.
What are some of the challenges associated with accurate pharmacovigilance?
One of the main problems we currently face is our lack of a shared mental state, resulting from our diverse systems. Broadly speaking, there is the pharmaceutical system; in the EU, this is governed by regulations. However, there are also individual, national healthcare systems; these are not governed by the same regulations. Therefore, we do not have joined leadership to ensure that we have a common approach to managing the pharmacovigilance of products across both systems.
Another problem we currently face concerns the naming of biological products. There are disagreements between the main agencies about how to name biological and biosimilar products. There is ongoing discussion to resolve these differences of opinions.
How may we work towards improved unique product traceability and risk minimization?
Technological advances, such as with bar and QR coding, particularly in the light of the EU Falsified Medicines Directive, will certainly improve the process. There is also a need to have better communication with those in healthcare concerning the purchasing of dispensing and prescribing technology; this is important for ensuring that this software is appropriately configured to capture important information such as the batch number of biological products. Improved communication will also ensure that these technologies are user friendly and have been appropriately user-tested, so that we can have confidence in the health care professionals using this software to track medicines.
What are some of the benefits to including patients in the pharmacovigilance process?
I am currently part of the Council for International Organizations of Medical Sciences (CIOMS; Geneva, Switzerland) group looking at patient involvement in drug development and safe use of medicines. It is noteworthy that there has been considerable progress in patient engagement in the lifecycle management of medicines, particularly in the USA, but also at the level of the European Medicines Agency (EMA; Amsterdam, Netherlands). This has enabled greater transparency and confidence of the public and patients in the way medicines are authorized and regulated. However, there is still considerable progress required to align the differences in opinion about when to involve patients.
I think patients will be very helpful for resolving some of the difficulties that we have around topics, such as what qualifies an important risk, what matters and what doesn’t. At the end of the day, the healthcare budget is not limitless; we need patients to help us make critical decisions about what are reasonable actions to take, such as in risk minimization, so that these do not become a burden on healthcare systems and interfere with access for new medicines.
"...patient input on what is considered an acceptable level of risk is critical."
What are some of the challenges associated with patient involvement in pharmacovigilance?
One of the main points of contention concerns the timing of patient involvement. It is understandable that sponsors might be anxious not to involve patients too early in the drug development process, until they are sure they have a viable product. However, it is apparent that it is important to engage patients as early as possible in the development of new medicines; patients can aid in the definition of the ideal product profile and in the development of patient preference data and outcomes. This is going to be an increasingly important component of determining benefit–risks of future medicines.
Another barrier to patient involvement concerns the huge need for patient training. There have been important initiatives, such as the European Patients’ Academy (EUPATI; Brussels, Belgium) training initiative, that aim to train patients in the clinical development process; this has been very resource intensive. Going forward, it is going to be a big challenge working out how to resource the training of suitable patients to get engaged in drug development and the safe use of medicines.
How may we apply systems theory in risk management?
In general, there has been inadequate adoption of systems theory and human factors thinking throughout the pharmaceutical sector. This is particularly important in the area of risk management where conventional approaches have not succeeded and where we can be dealing with very significant risks – such as teratogenicity or agranulocytosis when patients have a bone marrow wipe-out. When there are associated risks that society is completely agreed are unacceptable, then it is worthwhile adopting a systems design to enable us to see how we can properly integrate approaches to risk minimization across both the pharmaceutical and healthcare systems.
"I think that, in the future, better design, taking a more human-centered approach into account to assure safe and effective use of medicines, is required."
One of the first steps toward this is to define the hierarchy by which the system is controlled, to determine who is accountable and who is responsible. The next step would then be to determine where the control steps are and what tasks are required to implement constraints within the necessary processes to ensure effective minimization of risk.
How do you see the pharmacovigilance field evolving in the future?
I think the big driver will be the increased involvement of patients. I think this will challenge us on some of the assumptions that have been made; it was previously assumed that regulatory agencies acted as a surrogate for the patient. However, it is now apparent that we have moved into a different sphere of thinking that is more nuanced and complex; the decisions about what is effective do require patient input. Further, patient input on what is considered an acceptable level of risk is critical.
It was apparent from the patient hearings arranged by the EMA – concerning sodium valproate and fluroquinolone use – that patients were frustrated that their concerns were not being heard by the relevant stakeholders. Patients felt that they were observing and identifying breakdowns in risk minimization that were not being addressed.
I think that, in the future, better design, taking a more human-centered approach into account to assure safe and effective use of medicines, is required. This will require leadership from the different stakeholders within the system; at this stage, although these leaders have not been completely identified, I know that there are ongoing discussions around how to better design the system.
Furthermore, new technologies, such as social media, have thrown up additional challenges with respect to how we use the data from these sources.
Artificial intelligence and automation will also enable us to examine large datasets more effectively and take a more active approach to the surveillance and interrogation of databases, not just for the purposes of safety, but also effectiveness and use of real-world data. It will be interesting to see how we deal with these aspects too in the future.
Statement of disclosures:
Edwards has no competing interests to declare.