Under the 21st Century Cures Act, which aims to accelerate research and development and ease drug approvals, the FDA must now consider how real-world evidence could support the approval of a new indication of a drug, as well as support or satisfy post-approval study requirements. Payers are also demanding more real-world evidence (RWE) to support product value and reimbursement. While hybrid studies offer the potential to overcome significant research challenges, there are, however, limitations that companies must overcome to reap the benefits of real-world data. 
 
RWE is data collected from clinical trials to identify the best treatment paths in clinical practice and analytics is used to uncover the pathways. In order to allow greater adoption of RWE in clinical and regulatory decisions, FDA Commissioner Scott Gottlieb said the agency will need to work with the healthcare system to change the way clinical information is collected.
 
Following the FDA’s recent finalization of guidance on the use of RWE, Mr. Gottlieb commented, “We need to close the evidence gap between the information we use to make FDA’s decisions and the evidence increasingly used by the medical community, by payers, and by others charged with making healthcare decisions. Ideally, we’d like to have a system where providers have the right incentives to enter clinically relevant information into electronic medical records (EMRs) at the point of care.”
 
Joshua Schultz, senior vice president and Worldwide Head of PAREXEL Access, discusses how the industry can better understand and make the most of real-world data services and what standards need to be established. 
 
 
Contract Pharma: How does RWE support new indications of a drug? 
 
Joshua Schultz: Real-world Evidence (RWE), which includes traditional primary data research modalities as well as Real-world Data (RWD) (which primarily include secondary sources such as electronic medical record and claims data), supports new indications in several ways. Areas of unmet need and indications of performance in off-label uses emerge in RWE that help pharma see additional opportunity with marketed compounds. Regulators are indicating that label expansion or new indications are one of the first areas in which they are prepared to work with sponsors to leverage RWE as primary data to support review and marketing authorization determinations.  
 
CP: What are the regulatory implications?
 
JS: The regulatory implications are substantial. Establishing the parameters for regulatory applications of RWD has the potential to be the force that ultimately facilitates a retooling of the way that we develop drugs. Phase constraints can truly be reduced. Decision making on the role of a therapy in the treatment of a disease and the potential impact on healthcare can be supported earlier in development. The time pressures built into 21st Century Cures, PDUFA VI and the 2018 EMA Guidelines will provide needed clarity to help industry decide where to make investments in the advancement of health data science. 
  
CP: What are some of the limitations of real-world data?
 
JS: Limitations to the use or RWD to fully meet evidence requirements alone remain. 
·      Heterogeneous data – including free text + lack of standards
·      The 3 “I’s”:  incompleteness, inconsistency and inaccuracy
·      Regional variations in access to data
·      Data ownership and data-use agreement status
·      Data privacy / patient-level authorization to access their data for research
·      Lack of standard unique patient identifiers to enable linking
·      The need for re-identification of data
·      Data are rarely present in one, single data source – requires data aggregation from multiple sources

CP: How can they be overcome?
 
JS: The complete solutions will unfold over a number of years. Meanwhile, near term activities that can advance the use of RWD include settling as an industry on a common patient identifier standard to allow us to link data. Clarity on data requirements for various use cases will also help. Needless to say, increasing the opportunity for patients to place their data into research would have tremendous opportunity. 
 
CP:What standards for RWE need to be established?
 
JS: The standards debate will also continue for several years. Furthermore, standards will vary by data use case. RWD is truly a paradigm shift and we cannot think in terms of the standards that we are able to define in RCTs where we fully control the data source and flow. RWD based standards must be flexible and relate to the data sources to realize the value of RWD. It perhaps makes more sense to pursue a range of data standards that we as an industry can agree on, and focus our resources on common, validated interoperability protocols that we accept. 
 

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As Senior Vice President and Worldwide Head of PAREXEL Access, Mr. Schultz oversees the global Late Phase business which provides clinical research services in the peri- and post approval phases, including IIIb/IV clinical trials, observational research, market access, medical communication and patient safety services.