Is Real World Evidence the Future for Large Cardiovascular Clinical Trials?

By Phil Galtry, VP, Clinical Development, General Medicine

Recently I was honored to take part in a panel discussion with cardiologists at the annual Global Cardiovascular Clinical Trialists (CVCT) Forum held in Washington, DC, which drew 475+ attendees. My co-panelists included Dr. Robert Califf, MD, former Commissioner of the US Food and Drug Administration (FDA) as well as Drs. Martin Cowie, Kirkwood Adams, Stefan James, Bernard Vasseur and others.

An important key message running through all of the panelists’ presentations was that Real World Evidence (RWE) is destined to change the future of cardiovascular research, particularly as cardiovascular outcomes trials (CVOTs) typically must follow thousands of patients over a number of years. 

The increasing generation of RWE in the cardiovascular space is further made possible through the use of “Direct to Patient” study designs. Additionally, eClinical platforms that put the patients themselves at the heart of data collection are becoming increasingly prevalent and their use in the chronic cardiovascular disease setting will be become increasingly important, saving significant time and cost in the delivery of long term outcomes data.

The FDA Framework for Real World Evidence provides guidance on how RWE can be used to support approvals of new indications for previously approved drugs, and to support or fulfill post-approval requirements. The FDA acknowledges that real world data  (RWD) can be used to improve the efficiency of clinical trials, and provides guidance into how the FDA will assess the fitness of RWD for regulatory decision making. 
 

A precedent has already been set with biopharmaceutical companies positioning themselves to be ready to present “Regulatory Grade” RWE both in the US and the EU. The acquisition by Roche of the healthcare technology and services specialist Flatiron Health (Flatiron) is a case in point. The drive for this acquisition by Roche was to ensure that they had access to the necessary RWE needed to support their key oncology brands moving forward as they broaden their indication base. It is also noteworthy that  the recent announcement by Flatiron and the FDA with regard to their renewal and expansion of their research collaboration agreement, the Information Exchange and Data Transformation (INFORMED) program, aims to  evaluate RWE, derived from de-identified patient datasets curated from electronic medical records (EMR), can help support regulatory decision-making.

Cardiovascular Outcomes Trials (which may also be required for diabetes therapies - and potentially for indications in obesity, rheumatoid arthritis, and testosterone replacement) are fantastically expensive trials to conduct through traditional means yet their importance is critical. 

At Syneos Health, we’ve long recognized that RWE can become a critical component in cardiovascular drug development, and we are on the cutting edge of developing approaches to both collecting real world data that can become evidence, as well as to perfecting applications of existing real world data that improve trial efficiency. 

For instance, one of the most powerful current applications of real world evidence is in helping to shape the protocol and in determining the feasibility of Phase II and III studies. We now routinely use RWD collected via EMRs of more than 60 million patients in this way through. The data are drawn from 50 healthcare providers in the US, Germany, the UK, and Asia who have already expressed an interest in clinical research. By “tweaking” the inclusion/exclusion (I/E) criteria in an analytical platform, we can test the impact of different parameters on the number of eligible patients. This “funnel analysis” might, for instance, reveal that some criteria “clash” with the unintended result that they exclude the majority of otherwise eligible patients. Once such an issue is highlighted, it might be possible to make relatively minor adjustments to the criteria to avoid disqualifying a large number of patients, considering, of course, the implications for eventual labeling. 

Key technology suppliers are developing in this space, bringing significant data access and analytical capabilities into play, as exemplified by a recent case study from TriNetX. TriNetX technology enables discoveries through the creation of real-world evidence. They combine real-time access to longitudinal clinical data with state-of-the-art analytics to answer complex research questions. Recently, they used their platform to demonstrate comparable results to a published study of a true clinical study looking at Lower Heart Failure Risk with SGLT2 Medications, demonstrating that SGLT2 medications are associated with a significantly lower risk of heart failure as compared to DPP4 medications

The analysis took ~1 hour to complete from query design strategy to running comparison, a completely different dynamic to the cost and time required to collect this data in the original study.  So the ability to generate these rapid insights can have a huge bearing on CV trial methodology moving forward, including “wargaming” several potential study designs prior to committing.

We can also use the same EMR database to accelerate patient recruitment. Because the sites registered in the database have already expressed an interest in trial participation, we can build an automated query that they can use to identify patients within their systems that meet the I/E criteria. 

To read more about Syneos Health’s take on the rise of the pragmatic clinical trial and how Real World Evidence fits into the 10 biggest trends shaping healthcare, see the “Accelerating Evidence” chapter of our new report, the 2019 Health Trend Ten.