January 11, 2019 | Real-world evidence is unarguably rich, but it’s also noisy and can be difficult to parse. But those challenges are worth overcoming says Cathy Critchlow. An epidemiologist by training, Critchlow is vice president and head of Amgen’s Center for Observational Research. She and her team provide observational research methodologic expertise and strategic input to functions across Amgen including, clinical development, biostatistics, patient safety, medical affairs, health economics, market forecasting and digital technology.

With 14 years’ experience in observational research at Amgen, Critchlow is sure there are important clinical questions that can’t be answered by randomized clinical trials and crucial data available from patients in clinical practice settings. Real-world data won’t supplant clinical trials or prospective observational studies, she says, but it will play an important role in complementing them.

On behalf of Clinical Informatics News, Marina Filshtinsky spoke with Critchlow about how real-world evidence is changing clinical research, where it’s gaining ground, and what work is left to be done.

Editor’s note: Marina Filshtinsky, Executive Director of Conferences at Cambridge Healthtech Institute, is planning a track dedicated to Late Stage Research Strategy and Operations at the upcoming Summit for Clinical Ops Executives, SCOPE, in Orlando, February 18-21. Critchlow will be speaking on the program. Their conversation has been edited for length and clarity. 

Clinical Informatics News: We know that real-world evidence is increasingly used in regulatory submissions seeking approval for new indications, label extensions, new product marketing authorization. Why the recent traction? What has changed compared to a couple years ago?

Cathy Critchlow: I think a couple of things. One is the passage of the 21st Century Cures Act at the end of 2016 which requires FDA to develop a framework and guidance for evaluating real-world evidence to support approvals of new indications for previously approved drugs.  In addition, the Prescription Drug User Fee Act (PDUFA) VI establishes a public process for stakeholders to provide input to the FDA as it develops guidance on use of real-world evidence in regulatory submissions.  We’ve also realized that there are questions that perhaps cannot be addressed by randomized clinical trials, and data collected from patients in clinical practice settings may be more generalizable than data collected in clinical trials. Those two realizations and the legislation have led to greater receptivity on the part of regulatory agencies to consider real-world evidence, and also provides an opportunity for industry to offer potential use cases that might be amenable to regulatory decision making.

Does Amgen have a system in place that would allow you to take advantage of real-world evidence throughout a medicine lifecycle?

We do. In my group we have what we call our Data and Analytic Center, which houses a Data Lake containing numerous datasets that have been converted to a common data model. We've layered on top of that a suite of analytic tools that enable us to focus on important stakeholders and business questions that can be addressed by the data. For example, one group within the data center provides descriptive epidemiology data such as disease incidence and prevalence for many functions. Other groups focus on our key internal stakeholders, including patient safety, clinical development, biostatistics, medical affairs, health economics, market forecasting and digital technology.  The Product Leads in my group serve as liaisons between the Data and Analytic Center and the cross-functional product teams. In this way, we're able to utilize real-world data on our data platform to address business questions across the product lifecycle, starting from first in human to the end of life cycle.

Do you think that the rise of real-world data and real-world evidence will lead to decreased number of prospective observational trials?

Potentially, although not necessarily. Data from secondary data sources are increasingly available, and our ability to link data sources to capture the broader patient experience is growing. However, there are a number of situations where data can only be acquired in prospective observational studies, for example, where specific outcomes including patient-reported outcomes, are not available in real-world or secondary datasets.

How will real-world evidence change the role of patients, the place of patients, in clinical and observational research? Will it increase or decrease patient centricity?

I think the growing focus on patient centricity will lead to more conversations with patients to identify what clinical outcomes are important to them. Conducting studies in clinical practice settings will enable collection of information that is now not captured in certain datasets, for example degree of pain experienced, days of work missed or other types of patient reported outcomes. I think the extent to which clinical trials begin measuring endpoints that are more important to patients than perhaps some of the current outcomes assessed will make patients feel that they have something to gain by participating in clinical research.

What should we be working on now?

The use and impact of real-world evidence will increase dramatically. It will be important to work on processes and methods that increase the validity of such evidence. We need to build consensus on topics such as data quality. What will be the standard of evidence for use of real-world evidence in regulatory decision making? How do we increase interoperability between data sources? How do we create linkages to more comprehensively capture relevant patient data in accordance with data privacy laws? There's a lot of work needed on both the technical side as well as the methodological side to convince decision makers that real-world evidence is addressing the important clinical questions in a robust and valid manner.