StemCell Therapy

The use of real-world data (RWD) and real-world evidence (RWE) in regulatory decision-making may seem more aspirational than practical at times, but that state of affairs is changing rapidly. Wendy Rubenstein, director of personalized medicine at the U.S. FDAs Center for Devices and Radiological Health, said contemporary versions of these real-world sources of evidence are of progressively higher quality in recent years, and thus RWE and RWD may soon hit their strides as mature sources of data with which regulators are increasingly comfortable.

Rubenstein was speaking on a recent webinar hosted by the Medical Device Innovation Consortium, the public-private partnership between the FDA and device makers with the objective of modernizing regulatory science. The theme of the webinar was a framework developed by MDIC for the use of RWE and RWD for in vitro diagnostics, and Rubenstein said that for perhaps the majority of randomized, controlled trials, the benefit is generally diluted when that therapy or diagnostic is rolled out for routine clinical use. The external validity of the results of studies is not always sufficiently vigorous to withstand translation into general clinical use, particularly when the enrolled study population fails to reflect the population(s) that will use or receive the device, she said.

Collection of RWD in the premarket phase should help mitigate these problems and more accurately predict similar results in real-world settings, Rubenstein said, adding that RWDs reputation has not always been the best and has maybe got a bit of a bad rap as a consequence. Recently, however, the increasing quality of RWE and RWD is changing minds, and Rubenstein said the process involved in developing the MDIC framework is helping us get to that higher level.

Pandemic has quickened stakeholder interest

The FDA has given the nod to more than 100 diagnostic emergency use authorizations (EUAs) in connection with the COVID-19 pandemic, and Rubenstein said the pandemic has had the effect of unifying the purpose of regulators and test developers alike. COVID-19 can actually result in driving the community toward a common purpose of generating evidence on real test performance for molecular diagnostics for the SARS-CoV-2 virus, she said, but this will require a definition of common data elements to support use purposes. Still, Rubenstein advised that the pandemic is likely to come to an end before stakeholders can stand up a fully developed infrastructure needed to make routine use of RWD.

In other words, theres an opportunity to use the activation energy created by the pandemic to build an infrastructure that will extend beyond COVID, Rubenstein said. However, all of this will require the use of the Standardization of Lab Data to Enhance Patient-Centered Outcomes and Value-Based Care (Shield) project. Shield is another public-private partnership, and is focused on data lab standards, and is one of the pillars needed to make the data accessible. The development of mapping manuals for logical observation identifier names and codes (LOINCs) will also prove crucial because of a considerable amount of ambiguity with regard to LOINCs, which has up to now has made it difficult to aggregate data about a tests routine clinical use, sometimes even within a health care organization.

Danelle Miller, director of global regulatory policy at Indianapolis-based Roche Diagnostics Corp., and chair of the RWE working group (WG) at MDIC, made reference to the August 2017 FDA guidance for the use of RWE to support regulatory decision-making. Miller said industry welcomed the FDA guidance enthusiastically, largely because the guidance goes a long way toward clarifying when RWE can be leveraged for regulatory decision-making. She said the MDIC framework represents years of hard work and robust discussions among the parties, including industry, the FDA and the Centers for Disease Control and Prevention. The comment period for the MDIC framework closes June 15.

The scope of the framework is largely limited to the current landscape for RWE and real-world data (RWD) and, in the case of the latter, how it can be used for both premarket regulatory decision-making and for postmarket issues. The framework also proposes and approach for evaluating the relevance and reliability of RWD to assess data quality for regulatory decisions, and proposes a few study designs and methods for generating valid scientific evidence.

The task for the work groups included development of a glossary for RWE and RWD, as well as a survey to determine how IVD manufacturers are currently using RWE throughout product life cycles. The WG undertook a literature search for use of RWE and RWD, but there was a considerable amount of effort put into a description of the requirements for data quality and the methods for using RWD.

Alternative study designs available

One of the complicating factors in leveraging real-world sources of evidence for diagnostics in the premarket phase is that diagnostic studies dont often strongly resemble the types of trials employed for therapeutic devices. One approach to overcoming this limitation is the use of a virtual clinical performance study, which can be used to support premarket approval or clearance of an IVD. The MDIC paper spells out several other approaches as well, but among the regulatory considerations for any of these studies is whether the data are fit for the purpose at hand.

The assessment to determine whether those data are fit for purpose includes a determination of whether the data are both accurate and complete, and whether those data meet key reliability and relevance criteria to support the sought-after regulatory decision. Test developers should also ensure they are using data standards the FDA will accept, and may want to engage with the agency via the Q-submission process to clear out any potential issues before the developer invests more than a modest amount of resources toward the application.

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Real-world data coming into its own despite bad reputation in times gone by - BioWorld Online

This entry was posted on July 11, 2020 at 12:49 am and is filed under Personalized Medicine. You can follow any responses to this entry through the RSS 2.0 feed. Both comments and pings are currently closed. |