Transforming healthcare with real-world evidence (RWE)
The healthcare industry experienced a revolutionary shift when it switched from practising medicine as an art to evidence-based medicine, which is based on relatively simple randomised clinical trials to determine which treatment option was safe and effective. Through the years, evidence-based medicine became the gold standard for clinical development. However, this method has become less feasible over time – not only are people living longer and developing more chronic conditions, but more treatment options are also becoming available for a single condition. Now, instead of deciding whether a treatment is safe and effective, doctors must also determine which treatment option is the best suited (accounting for efficacy, safety and cost) for a patient based on their unique conditions – this is known as precision medicine. With healthcare costs already at their peak, trying to apply randomised clinical trials to this challenge would skyrocket costs, as we would have to evaluate all subgroups and compare all treatments.
In recent years, this gold standard has also received numerous criticisms – for instance, in 2018, the US Food and Drug Administration (FDA) quoted, “the clinical trials system is broken,” calling for the industry to embrace more collaborative studies that better serve the interests of patients. Similarly, the US Congress has highlighted several drawbacks to traditional clinical trials, including firstly, the high costs involved in conventional drug development (drug development costs now amount to more than $1.3 billion). Secondly, the results from the trials, which may suffice to support regulatory approvals, do not necessarily reflect real-world medical practice, and these trial participants do not reflect the diversity of the treatment’s real-world settings. Lastly, due to the costs, time and complexity, only small numbers of clinical trials with a limited number of patients can be conducted, posing an additional drug development bottleneck. Thus, this is where real-world evidence (RWE), with the combination of powerful artificial intelligence technologies, can help close this evidence gap.
What is RWE?
The FDA defines RWE as, “healthcare information derived from multiple sources outside of typical clinical research settings, including electronic medical records (EMRs), claims and billing data, product and disease registries and data gathered by personal devices and health applications.” Real-world data such as these can complement our existing knowledge derived from traditional clinical trials, while also overcoming their limitations, thus leading to the creation of an entirely new industry that is focused on the acquisition, analysis and application of patient and drug data to generate insightful RWE.
RWE has many applications across the product life cycle, from research and discovery to commercialisation. Life sciences companies can use real-world data to support real-time decision-making for public safety or to support a brand through real-time strategic decision-making. Incorporating RWE in drug development programs can inform superior protocol design, reducing the number of expensive protocol amendments and facilitating the use of synthetic control arms to decrease drug development costs and accelerate development timelines. Similarly, RWE could reduce the cost of evidence needed for filing and accelerate label expansion, which has been a major hurdle for pharma companies.
Indeed, there is a plethora of cost savings that can be attained through the effective use of RWE to make the pharma development and commercialisation pathway more efficient; a 2016 report estimates that with RWE, pharma companies could have the potential to save up to US$1 billion per year in drug development costs.
RWE in the pharmaceutical sector
Executive leadership teams in pharma have long considered RWE as an important part of their strategy, in fact, 90% of the companies in the survey done by Deloitte have made major investments in RWE. However, it is worth noting that there has been a shift in focus to drive earlier use of RWE in the product life cycle. This is attributed to the fact that 70% of clinical trials are affected by enrolment complications, and every incremental week’s delay results in a loss of US$300,000 in revenue.
Across the product life cycle, we have seen big pharma take advantage of RWE through a broad range of applications:
- Merck and Pfizer used a synthetic control arm (consisting of results from a retrospective observational study) to support the results of their single-arm trial to demonstrate the efficacy and safety of using Avelumab to treat Merkel cell carcinoma. They were able to shorten the approval time by 1.8 years (compared to the median for other drugs in an expedited approval program) to only three years;
- Pfizer, in collaboration with Flatiron and IQVIA, evaluated EMR and claims data to prove the safety and efficacy of using Ibrance to treat male breast cancer patients, which was originally approved to treat only female breast cancer patients. This work enabled them to obtain FDA approval in less than a year and for a fraction of the costs of performing clinical trials;
- Since 2018, Novartis, through their partnership with TriNetX, has used a cloud-based platform to conduct state-of-the-art analytics on real-world data to conduct early feasibility analyses over 150 clinical trial protocols across multiple disease areas, in a bid to streamline their drug development operations that have cost them more than US$5 billion per year.
From a regulatory standpoint, COVID-19 has been the single greatest catalyst for the acceptance of RWE. Recently, the FDA has identified RWE as the best solution for addressing the dysfunctional clinical trial processes and has made major steps toward acknowledging that while clinical trials are still very much relevant, they are not the only way to evaluate the efficacy and safety of a product. For instance, the FDA has partnered with Aetion to use their platform for the assessment of COVID-19 inpatient medical products. This would enable the FDA to assess inpatient COVID-19 treatments in real-time while also developing a framework and infrastructure that will support their data modernisation goals.
Moreover, since COVID-19, the FDA has released two draft guidance documents that provide critical information to developers trying to use RWE – a vital step toward a greater plan that will in due course transform healthcare. We can see that the FDA is not the only regulatory body making moves to integrate RWE. The European Medicines Agency (EMA) stated in their Regulatory Science to 2025 document that one of their objectives is to promote the use of RWE in decision-making, and in 2020, published a guideline on registry-based studies enhancing the role of RWE. Most recently, in June 2022, the UK’s National Institute for Health and Care Excellence (NICE) released their draft RWE framework for public consultation as part of their larger five-year strategic plan, which focuses on the use of RWE to close evidence gaps, improve NICE’s decision-making and help get innovative health technologies to patients. The promotion of new policies surrounding RWE further cements the importance of RWE within organisations and this momentum is continuing to build across the healthcare ecosystem.
M&A and funding landscape
Investors have not been slow to see the potential of RWE companies with several significant transactions in RWE companies:
- January 2022: Aetion acquired synthetic data provider, Replica Analytics. This acquisition would enhance Aetion’s technology portfolio to open access to previously inaccessible real-world data;
- March 2021: Evidation Health closed their $153 million Series E growth funding led by OMERS Growth Equity and Kaiser Permanente Group Trust to fund its virtual health capabilities through the combination of real-world patient data from multiple sources;
- June 2019: PPD Unit, Evidera, acquired Medimix. The addition of Medimix “enhances Evidera’s ability to leverage data to provide real-world evidence and insights for clients.”; 
- March 2019: TriNetX’s $40 million Series D funding round headed by Merck Global Health Innovation Fund. TriNetX is a global health research network that offers clinical research and enables discoveries through the generation of RWE; 
- April 2018: Roche acquired Flatiron Health, a company offering oncology-specific electronic health record (EHR) software, as well as the curation and development of RWE for cancer research, for $1.9 billion; 
- October 2016: Quintiles merged with IMS Holdings Inc. (now IQVIA) for $8.8 billion. One of the main motivations for the merger was to make the most of the increasing use of RWE in clinical drug development as well as other areas of the pharmaceutical market.
Overcoming RWE hurdles
Despite the significant advances made in the use of RWE in the healthcare industry, there are still many challenges to the success of RWE efforts. The most notable obstacle would be access to research-grade real-world data due to organisational silos and a lack of consistent data standards. This consequently leads to concerns over the accuracy and reliability of real-world data collection and gaps in real-world data sets. There is also the lack of standardisation of RWE analytics, which if not properly handled, could lead to poor-quality analyses, limited transparency into methods and biased findings. Moreover, there are also privacy concerns related to giving companies access to these large and extensive datasets.
However, pharma efforts to tackle these challenges have been tremendous, and they have done this through strategic partnerships with RWE companies, including:
- January 2022: Evidation and Sanofi extended their decade-long collaboration agreement, with this partnership to focus on building on their joint real-world data initiatives, targeted at co-developing datasets to develop and validate novel measures of health and wellness;
- August 2021: ConcertAI and Janssen expanded their data science collaboration to power rapid insights into more efficacious treatments for patients by utilising ConcertAI’s oncology real-world data and AI;
- August 2021: Aetion and Syneos announced a partnership to deliver regulatory-grade data and analytics-driven solutions to advance drug development and enhance patient outcomes;
- December 2021: Tempus and Janssen extended the scope of their agreement to improve the discovery and development of therapies for oncology indications using AI/ML and RWE.
In conclusion, we have now come a long way with progress on the adoption and widespread use of RWE, straying away from exclusive dependence on the traditional gold standard of randomised clinical trials. Never have external pressures been so high for the healthcare industry to continue to innovate without increasing drug prices. With the right technology and regulatory intelligence, RWE can be transformational for the healthcare industry. As different stakeholders utilise different data types in different ways, this data can provide valuable insights and evidence across the product life cycle. It will now be a question of breaking down the inefficiencies and information silos between different stakeholders and streamlining processes to support value-based outcomes and reduce costs.
- KAITIN, K. 2010. DECONSTRUCTING THE DRUG DEVELOPMENT PROCESS: THE NEW FACE OF INNOVATION. CLINICAL PHARMACOLOGY AND THERAPEUTICS 87(3):356-361.
- OLSON, M. 2019. CAN REAL-WORLD EVIDENCE SAVE PHARMA US$1 BILLION PER YEAR? A FRAMEWORK FOR AN INTEGRATED EVIDENCE GENERATION STRATEGY. JOURNAL OF COMPARATIVE EFFECTIVENESS RESEARCH 2020 9:2, 79-82
- DELOITTE INSIGHTS, 2022. RWE FOCUS IS SHIFTING TO R&D, EARLY INVESTMENTS BEGIN TO PAY OFF, FROM HTTPS://WWW2.DELOITTE.COM/US/EN/INSIGHTS/INDUSTRY/HEALTH-CARE/REAL-WORLD-EVIDENCE-STUDY.HTML