Randomised controlled trials (RCTs) have long been the gold standard for testing drugs, offering consistent data collection among a homogenous patient population. However, genomic advances, a surge in patient data, and pressures from the COVID-19 pandemic are driving more and more sponsors to explore the benefits of incorporating real-world data (RWD) into their clinical trials.
According to the FDA, RWD refers to any data collected outside the clinical trial setting, including electronic health records (EHRs), medical claims, and patient-generated data. Meanwhile, real-world evidence (RWE) is clinical evidence of the potential benefits or risks of a therapy derived from analysis of RWD.
Importantly, RWD is different from historical clinical trial data, which is evidence collected exclusively from past arms of traditional clinical trials. Synthetic controls arms—also known as external control arms or concurrent control arms—can include a combination of RWD and historical clinical trial data.
Overall, experts say RWD is most commonly incorporated in Phase IV trials, including for health technology assessments and payer approvals. However, the FDA’s 2019 framework on RWE in trials has piqued industry and non-industry interest alike in the potential of RWE in registrational trials, they add.
In 2022, there have already been more than twice as many Phase IV drug trials using RWD than in all of 2020, according to GlobalData’s Clinical Trials Database. During this same period, there has only been a modest uptick in Phase II and III studies using RWD. GlobalData is the parent company of Clinical Trials Arena, and the Clinical Trials Database compiles publicly available information on drug trials globally.
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As regulators gain more familiarity with studies using RWD, the door will open for more widespread adoption across more trials, explains Dr Vivek Subbiah, a clinical trialists at MD Anderson in Houston, Texas. “This digital era is ripe for innovation.”
Which therapy areas incorporate real-world data?
In oncology, genomic advances are beginning to render many RCTs obsolete by the time they are reported, Subbiah says. As the field moves toward treating smaller, biomarker-defined subgroups, many standards of care are constantly in flux, he adds.
By incorporating RWD, sponsors can more effectively measure how any treatment effect measures up against patients with highly specific genetic markers or standards of care, Subbiah explains. In cases where RWD is used in trials, the RWD source should be temporally and clinically relevant to the investigation arm and similar to a randomized study to minimize bias, he adds. Outside of trials, sponsors are using RWE to support internal target validation and patient optimisation, adds Arnaub Chatterjee, senior vice president of Medidata.
In addition, for cancers with no approved treatments—as well as many rare diseases—a placebo arm can be unethical, Subbiah notes. RWE can therefore help sponsors measure a drug’s effect in a disease where a RCT is unfeasible due to ethical concerns, small patient population, or both, he adds.
According to GlobalData’s database, oncology is indication with the highest proportion of drug studies using RWD in 2022. Oncology accounted for 24% of RWE studies initiated in 2022, followed by infectious diseases with 15% of trials and central nervous with 11%.
Decentralisation meets real-world data
Meanwhile, many studies using RWD also incorporate decentralised clinical trial (DCT) tools. According to the FDA’s 2019 framework on RWE, the agency considers patient-collected data—including mobile phone trackers, wearables, and biosensors—as an important form of RWD.
There are eight ongoing drug studies in oncology that also incorporate DCT elements, the most among any indication, per GlobalData’s database. The database tracks DCT elements including telemedicine, wearables, mobile applications, and remote drug delivery. Clinical Trials Arena has a tracker covering the biggest players and trends in DCT adoption, and a recent tracker update found that oncology was not the top therapy area using DCT overall.
What types of sponsors utilise real-world data?
New regulatory support, a deluge of data, and pandemic pressures have driven industry and non-industry alike to incorporate RWD. This is particularly true for non-industry sponsors, which accounted for 53% of studies using RWD in 2022 compared to 11% in 2013. In that same timeframe, the number of industry-sponsored trials initiated more than doubled from 2013 to 2022.
As for industry sponsors, AbbVie leads the charge with a total of 33 studies using RWD sponsored between 2003–2022, per GlobalData’s database. This includes 10 ongoing studies in indications such as hepatitis C and atopic dermatitis. Meanwhile, AstraZeneca has the most ongoing studies using RWE, with 13. Novartis and Bristol-Myers Squibb round out the four biggest industry sponsors.
Nevertheless, despite the sector’s clearcut enthusiasm, studies with RWD are not without their challenges. Real-world data is “all over the place,” Subbiah says, adding that sponsors must meticulously structure data to meet stringent eligibility criteria reflective of a clinical trial population. Matching baseline demographics and disease characteristics are essential for building a propensity score for accurate statistical analysis of RWD, Chatterjee notes.
Building datasets for the future
While regulators, industry, and academia are showing interest in RWE, it could be more data that ultimately leads the charge. There are hundreds of billions of terabytes worth of data, and our tools for synthesis and collection will only grow stronger, Subbiah says.
In this sense, more experience with RWD collection could form the basis for more widespread acceptance from regulators, Chatterjee adds. “There is a world in which standardised collection and data presentation to regulators will pave the way for more RWD-based submissions,” he explains.
Above all, the drug development is beginning to realise that the gold standard RCT model is not infallible. “At the end of the day, the goal of stakeholders is to come together and benefit patients,” Subbiah says. “The current system of randomised control studies for every clinical question is quickly becoming unfeasible.”
- While RCTs are still the gold standard for trial design, studies using RWD are valuable tools when factors such as changing standards of care and small patient subgroups render RCTs unfeasible.
- The most common therapy area for RWE studies is oncology, as genomic advances drive the sector towards precise populations that can be too small to measure in RCTs.
- Both industry and non-industry sponsors are showing increased interest in studies using RWE, with both sponsor types initiating more studies with RWE in 2022 than any previous year.
- As health data collection becomes more prevalent and standardised and regulators become more familiar with RWE, there will likely be a continued surge in RWE studies to compensate for the inadequacy of RCTs in certain situations.
Methodology: Trial results are derived from a text-based analysis in GlobalData’s Clinical Trials Database of hundreds of publicly available drug trial records incorporating RWE and/or RWD related terms.