By Vaishali Patadia, head of signal management & safety risk management CoE in global patient safety, Amgen
The use of real-world data (RWD) for rapid safety signal assessment is nascent. Yet, as the number of available RWD sources proliferates, so has regulatory and industry desire to leverage RWD to evaluate drug safety signals quickly and robustly with the benefit of potentially enhancing patient safety and public health. This growing emphasis has prompted such post-marketing pharmacovigilance efforts as the European Medicines Agency’s (EMA’s) DARWIN EU and the FDA’s Sentinel Initiative, for example.1,2
For sponsor companies, one of the chief benefits of applying RWD for rapid signal assessment is that it can provide a more accurate view of outcomes that should be expected within a given clinical scenario — not just a picture of the outcomes in clinical trials or those that are spontaneously reported. By adding greater context to a signal, RWD enables sponsors to make more informed decisions.
However, before RWD’s maximum potential for rapid signal assessment can be reached, the industry must overcome some sizable challenges. According to a soon-to-be-published summary of the current state by nonprofit industry consortium TransCelerate, those challenges include3:
- a lack of clear definitions and a framework for RWD rapid signal assessment,
- a need for acceptable alternatives to traditional, complete protocols for analysis using RWD, and
- a lack of RWD data availability and access.
Such gaps prevent sponsors from deriving valuable intelligence, making informed decisions, and taking necessary actions within company, regulatory, and other mandated time frames. The question is: How do we, as an industry, surmount them? Here are some opportunities to address each gap.
Rapid Signal Assessment Framework
The terminology and definitions used to describe RWD — including “rapid signal assessment” — are not yet entirely uniform. However, efforts to ensure more consistent language among global stakeholders are gaining traction. In fact, the International Council for Harmonisation (ICH) is working on a document to help standardize RWD definitions.4
More alignment on definitions and framework should reduce confusion — which, in turn, should help accelerate the use of RWD for rapid signal assessment. To start, a safety signal, as defined by the EMA, is "[i]nformation on a new or known adverse event that is potentially caused by a medicine and that warrants further investigation. Signals are generated from several sources such as spontaneous reports, clinical studies, and the scientific literature." In turn, TransCelerate’s RWD rapid signal assessment initiative adopted the EMA and FDA definitions of “safety signal assessment,” describing it as “the process of evaluating a validated signal by considering all available relevant evidence from different sources to confirm or refute a signal.”5 The group also had to align on how to define a “rapid” signal assessment. It eventually agreed to describe it as anything faster than an organization’s existing assessment process timeline.
In reality, everything about the safety signal assessment process takes time, whether querying and analyzing reports from internal and publicly available spontaneous database, requesting insights from epidemiologists, reviewing literature, or writing and reviewing a protocol for RWD analysis, etc. Much documentation is typically necessary when using RWD, as well. Yet sponsors usually must complete a signal assessment within 14 days to 90 days.
Given current processes, that is hardly enough time to work with the information in spontaneous databases — let alone put together a formal, protocolized RWD analysis. Before RWD can be used meaningfully for signal assessment, sponsors must be able to speed up the process. Therefore, a framework could facilitate RWD use to assess signals sooner while preserving all necessary scientific rigor and documentation.
With a shared understanding and communication of concepts and processes, sponsors should be able to understand potential risk impacts faster and more efficiently. Consequently, over the next several months, TransCelerate’s RWD rapid signal assessment initiative aims to clearly define a framework and make it publicly available for industry use.
The group believes some opportunities for the expedited use of RWD in signal assessment may lie in the preparatory work involved. For example, sponsors could identify which data sources are appropriate for their product and ensure that access to them is ready to go should a signal appear. Likewise, sponsors could predefine patient population cohorts. For a study that includes people with type 2 diabetes, for instance, they could decide up front which codes will be used to define the population for any necessary signal assessment.
The complete signal assessment process will be examined, looking for efficiencies that could make it fast enough to use RWD and still meet mandated timelines. Alongside the framework, potential solutions for expedited protocols and data access will be explored.
Alternatives To A Complete Protocol
One primary barrier to the rapid use of RWD for signal assessment is uncertainty about whether health authorities (e.g., FDA or EMA) will accept alternatives to a full protocol — such as a minimal protocol or a non-protocolized approach — for RWD studies. Hence, the RWD rapid signal assessment initiative intends to engage with regulatory agencies to consider ways to streamline the protocol process.
It is always a best practice to seek early engagement with health authorities on development programs that include RWD and/or real-world evidence (RWE).6 Therefore, through partnerships with global health authorities, the initiative’s eventual goal is to offer guidance to the industry about the types of analysis that could appropriately leverage pared-down documentation.
For example, could there be certain instances in which health authorities would find it sufficient to document just the variables and methodology? Could protocol templates be employed in certain circumstances? It will be exciting to see the solutions discovered through these collective conversations.
Better Data Availability And Access
Working with scientific alliances such as the European Health Data & Evidence Network (EHDEN) or the Observational Health Data Sciences and Informatics (OHDSI) collaboration may be crucial for sponsor companies that wish to use RWD for rapid signal assessment.7,8 These groups strive toward common data models and standards and offer education and open-source solutions.
However, some organizations may need to become more familiar with how to approach a group such as OHDSI to request data assistance. Thus, the RWD rapid signal assessment initiative also aims to explore whether it might be feasible to draw upon its collaborative strength to build bridges with organizations like OHDSI, EHDEN, and others. If the idea is deemed viable, the hope is that the effort will ultimately help sponsor companies effectively engage such groups to gain greater access to data and data expertise.
Opportunities For A Faster Approach
Rapid analysis of RWD holds great promise for improving safety signal assessment. Offering an efficient framework could go a long way toward overcoming the limitations of traditional databases and processes.
Finding practical solutions to enable rapid signal assessment is a challenging task, of course. It can’t be done in isolation; it requires collaboration among multiple industry stakeholders. Working together, efforts are underway to identify opportunities to better harness the power of RWD — and, hopefully, improve patient safety and public health.
About The Author:
Vaishali Patadia, Ph.D., MPH, MBA is an executive director, head of signal management and risk management center of excellence, global patient safety, at Amgen. She is also the lead for TransCelerate’s Rapid Signal Assessment using Real World Data workstream.
Patadia has 22+ years of experience in pharmaceutical and biotech companies. She has a strong leadership track record with broad experience across patient safety, including signal management, risk management, benefit-risk assessment, and pharmacoepidemiology. She has extensive experience in leading change, building and growing global teams, mentoring, teaching, as well as in the design and implementation of innovative tools and processes in pharmacovigilance and pharmacoepidemiology.