Reaching Consensus on Core and Local Implementation


Risk Minimization Programs are a part of the Pharmacovigilance strategy to achieve positive benefit-risk profiles for medications. According to the EMA GVP Module V, the benefits need outweigh the risks which considers the impact on the individual, seriousness of the risk, and the general impact on public health. And so, the primary aim of the Risk Management Plan (RMP) guarantees that the benefits outweigh the risks by way of appropriate risk management planning throughout the medicinal product’s life cycle.

The RMP is a dynamic document that should be continuously assessed. There is a cyclical aspect of identification, evaluation, selection, and planning of measures, implementation of those actions, and the collection of results to then analyze and repeat the process with the newfound data. This includes the added safety concerns where necessary, and, as the safety profile is updated, the reclassification or removal of those safety concerns needs to then be recharacterized.

Companies are required to have and implement risk minimization measures, but there isn’t clear guidance on HOW to implement them. The regulatory environment is tightening its reins on use of medicinal products, yet there are various ways of understanding and addressing the key factors that make or break the success of a program. In this article we will uncover the range of actions and documents linked to implementing activities from the RMP, specifically Additional Risk Minimization Measures (aRMMs). This includes the core implementation, the local implementation, and a solution to gain insights into the product’s safety profile under real-world use.

Implementing Risk Minimization

Risk minimization Functions involve a wide range of activities and persons, and the task of developing and implementing these activities escalate with each adaptation or version. Consider the variation alone in the reports, the differences in healthcare systems, cultural terminologies, and regulatory differences, plus the persons involved; all of these lend to the complexity of successful implementation. To address this complexity, many companies leverage a Core Implementation Plan. The Core Implementation is the way in which the risk minimization measures will be implemented, and the Local Implementation Plan will capture any adaptations to that plan at the local level.

Since these measures are scaled nationally, the Local Implementation Plan (LIP) has varying degrees of risk minimization activities to account for in addition to the Risk Management Plan (RMP). However as this sits underneath the Core Implementation Plan (CIP), it is important that the local implementation adheres to the requirements of this document. These risk minimization activities often involve professionals outside the medical or regulatory functions, and so the need to monitor and manage effective guidelines are critical to its performance. Data on the performance of these activities is also required for other parts of the PV system, for example, the EU QPPV, assists in their role and oversight of PV system performance and product benefit-risk balances. The back and forth in communicating, coordinating, and collaborating keeps the local and global teams in sync only if there is a measurable way to track these cross-functionalities.

What Counts for Successful aRMM Distribution?

Risk minimization measures are interventions intended to reduce or prevent adverse reactions. These measures can be either routine measures or additional measures. Additional risk minimization measures (aRMMs) are used to improve the benefit-risk profile of medicines. The process aims to improve the benefit-risk profile by maximizing the balance of risk to benefit, exclude patients where use is contraindicated, and educate the target audience about the safe and effective use of a product.  These aRMMs can vary in nature, for example, educational tools can be directed either at healthcare professionals or at patients/caregivers to provide information associated with the product and its safety concerns, all geared toward minimizing the risk associated with that safety concern.

Risk minimization measures are considered effective under two measurable categories – process and outcome indicators. Process indicators gather evidence and provide insight into the program’s execution and any impacts on behavioral observations. These implementation metrics are identified and tracked, to improve the overall process and assess what measures did or did not lead to the controls of specified risks. For example, metrics for timeliness and completeness of RMP Educational Materials are common process indicators. On the other hand, outcome indicators provide an overall measure of the level of risk control resulting from the established risk minimization measures. This could be something as simple as assessing prescriber knowledge about a particular action related to a safety concern, done through a web-based or in-person survey for example. As these processes aim to minimize risk to patient safety use, it’s crucial to have a means of accounting for all the contributing data at both the global and local level.

Central to Local Implementation

Risk management programs, including the implementation of aRMMs, are typically carried out in a variety of countries with different measures of implementation required at multiple levels and often by multiple parties. The Core Implementation is set and distributed out to local affiliates. At the local level Orbit can track variants and adaptations, which adhere to the core materials but vary in its adaptations. Supporting and maintaining the central to local implementation activities is a major pain point, wherefore it is critical to have a system that allows for timely access to information, with clear expectations, and an ability to report back to global with key data points.

Largely overlooked is how to best apply this central plan in a way that is flexible enough for local adaptations yet adheres to the core components of the implementation plan. After the core elements are defined, frameworks are distributed to produce achievable outcomes under real-world settings. Tools such as Dear Healthcare Provider Letters (DHCPs), educational programs, clinical aids, etc., are all necessary for successful program implementation and thus need to be documented and monitored.

There is a great need to synergize these activities from communication methods to receipt by various audiences, that are not only effective but also accommodate the necessary local adaptations. The multiple information sources and outcome measures are necessary to support the overall quality, use, and impact of these programs. As is evident, the coordination of the people, processes, and systems are necessary parts for successful implementation.

Current Status

These predefined metrics are identified and tracked over time. However, the disparate tracking over time is where we run into the heart of the problem. Although most companies are tracking activities, it’s done across multiple, siloed applications, which has proven to be inefficient and fragmented. It is understood that companies are using various methods like Outlook, Excel, and SharePoint, or they are completely outsourcing to a third party, of which neither is optimal. The disparate tools lend to inefficiency, and outsourcing tends to be rather costly.

Access and visibility end to end alleviates the back and forth, as the living document is accessed and shared by all. As it stands, there are systems that have been implemented outside of web-based tools, but nothing functionally quite like Orbit.

The Recommendation

The success of risk minimization efforts will need to be measurable, not only its processes, but also its outcomes. As mentioned above, process and outcome indicators provide insight into the program’s execution, and behaviors such as specific testing, patient and/or prescriber receipt documentation, and understanding of risk information procedures from follow-up through enrollment, are contingent on assuring the product’s safe use. Orbit can keep track of all these steps in one place.

Quality systems are necessary to collaborate these links across multilevel, multi-stakeholder programs, with metrics that indicate the program’s reach, adoption, and implementation by way of tracking. These factors provide valuable information for future programs and enhance programs to be established at the local and national level. Orbit does all of this while reducing the amount of work it takes to support local affiliates, and provide oversight.  With an adequate means to track, implement, and manage these variations, it is necessary to modernize your current process and Orbit is answering that need.