Bridging The Evidence Gap
AstraZeneca's Head of Real World Evidence shares the story behind AZ's seminal RWE study and casts his projections on the future
Observational studies are having a moment. The value of more descriptive and less rigidly collected data is increasingly being appreciated by pharmaceutical companies, who also recognize its complementary role to traditional randomized controlled trials. Last year, a survey by intelligence research company Cutting Edge Information found that the vast majority (82%) of pharmaceutical companies were conducting or planning to conduct an observational study.
AstraZeneca surprised many when they launched the large (300,000 participants) CVD-REAL real world evidence study to demonstrate the effectiveness of one of the most recent class of diabetes medicines, SGLT-2 inhibitors (SGLT-2i). The striking results, published in March last year, ultimately demonstrated that treatment with SGLT-2i significantly reduced mortality and hospitalization from heart failure in a broad range of patients. AstraZeneca is investing its scientific energy into studies of this nature to ensure that real world data can be used to bridge the gap between clinical trial data and real world patients.
The impetus for the study was one of sheer necessity, says Sajan Khosla, Head of Real World Evidence at AstraZeneca – a bid to address the gap created by the inherent time lag of RCTs.
“The reason we embarked on this study was because clinical trials that tend to be carried out in this space tend to take about two to three years to execute, so there was this knowledge gap relating to how this class of drugs was working in the heart failure patient population. We knew from feasibility counts the observational data sets had the clinical parameters to perhaps start to bridge that gap using real world evidence data.”
“It had quite a profound effect, not just for us as an organization but also the entire industry and how we collect and establish real world evidence as this bridge from RCT data back to the real world population, especially in places where the evidence hasn’t yet been generated by the RCT datasets. It provides us with a mechanism of doing the right thing for the patients, getting the evidence to the patients, but also that we are building momentum in the right places, so when the RCT data does some out, it is more confirmatory of the observations we received within RWE data.”
Industry has been historically risk averse to disrupt the status quo when it comes to gathering evidence, for myriad reasons, he adds.
“With the regulatory environment and financial environment, but also because of the competitive environment, we have got quite a number of reasons not to do things differently. Until you start to probe and understand why this is, only then you start to realize that the answer is that this is just always the way it’s been done. That means there is room to change stances.” Khosla also maintains that as pharma continues to attract talent from a broad array of backgrounds and with a wide breadth of skills and experience, this will ensure an enhanced understanding of the value of real world evidence.
“We are seeing the rise of people within the organization who have a mixture of experiences. The industry is attracting people from public health, hospital systems, people that really understand the value and potential of this data. This is changing the dynamic within the industry.”
Externally, supporting the regulators, helping them understand these datasets and what they have to offer, represents another challenge. This will necessitate a stepwise approach, says Khosla. Last year, AZ began creating guidance for its clinical trial specialists around the use of RWE within the RCT context, commonly known as pragmatic clinical trials.
“Our RCT design teams are getting clarity about the use of real world data. We have generated guidance and received external validation of that guidance from senior regulatory experienced individuals. We are proposing that we step towards the use of real world data to accelerate the way that we run randomized clinical trials and then use that as a stepwise approach to observational research data analysis.”
This means that observational studies are set to maintain their unstinted growth in popularity across the industry. Khosla is quick to assert, however, that this data has “a unique space”. “It is not a silver bullet and cannot be applied to all cases; it needs to be used in a complementary way where gaps manifest. It’s never going to replace the gold standard RCT data but in certain spaces there are application of this data to accelerate the way that we generate RCT data.”
By its nature, real world evidence is easier to collect than that within an RCT, but expert oversight is necessary to ensure its usefulness, not to mention its credibility. Khosla believes industry must invest strongly in observational studies so that their true value can be realized.
“On one hand I am very excited but at the same time I am concerned that we need to maintain scientific scrutiny of it too. Once a study leaks into the public domain that is poorly designed and executed and has anomalous observations, that is the point where we start to lose confidence. We need to really encourage the industry to leverage these data but also ensure that we have good processes and procedures in place to ensure there is scientific scrutiny. You need to train your scientific teams to be able to demonstrate why something like CVD-REAL is important and the value that the likes of these observational studies have been able to generate. This is important from scientific execution right through to medical communication.”
Sajan Khlosla will be sharing his insights at the Real-World Evidence and Access Europe 2018 event in April
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