Real World Evidence on the Rise

To understand the evolution of RWE and where it’s going next, we spoke with Catia Proenca, RWE Director at Alira Health. Catia has over 11 years of experience in pre-clinical Research, RWE, and Market Access, across the pharmaceutical industry, consulting, and academia, and holds a Ph.D. in Neuroscience from the Weill Cornell Graduate School of Medical Sciences, and a post-graduate diploma in epidemiology from the London School of Hygiene and Tropical Medicine. Catia has a market access lens on RWE and brings that knowledge and perspective to help clients with their RWE needs.

How has RWE traditionally been used in drug development?

RWE is commonly used in multiple ways. One is to describe the epidemiology of a disease: how many patients are suffering from the disease, for example. Which can help health authorities gauge the impact of the disease in the overall population.

RWE can also be used to understand the economic burden of a disease on a healthcare system; for example, by uncovering how many hospitalizations a disease causes per year in a specific region, state, or country. This helps to inform financial planning and resource allocation.

Another typical use of RWE is to show how a technology is being used in the real world. In a clinical trial, there are very strict inclusion and exclusion criteria, but when a drug goes to market and is available to be prescribed, patients with different baseline characteristics will be exposed to the new technology. People with different comorbidities will have access to that technology. RWE is frequently used to study a drug after it’s been marketed, to assess not only usage but also the impact of having introduced that technology into the system, which is important information for health care systems, the so-called post-marketing studies. When they approve a new medicine at a certain cost to their budget, there are opportunity costs: funds are allocated to that new technology and not to others. An example of is the French guidance document on the design of RWE studies, which focuses on measuring the impact on the physicians and patients, as well as the economic impact of having that product on the market.

Another major use of RWE is to differentiate a technology from the competition. If a new product comes on the market, a sponsor can use the data they’ve collected on the use of their product to demonstrate the positive outcomes to prescribers and potential patients. Making the RWE available helps strengthen the value of the existing product in that disease area.

One very famous example of a very long (still ongoing) RWE study is the Framingham Heart Study, which contributed greatly to our overall understanding of heart disease. Thanks to this study, we identified what are now widely accepted risk factors of heart disease (e.g., high blood pressure and high cholesterol), the development of treatments, and to what is now common knowledge concerning the prevention of heart disease, such as having a healthy diet and exercising. This is a clear example of how capturing data from patients, in a longitudinal and long-term fashion can advance our knowledge of diseases.

How has the RWE situation changed recently?

The RWE situation has changed a lot in the past years. RWE is increasingly influencing decision-making about drug technologies. Both the Food and Drug Administration (FDA) and European Medicines Agency (EMA) have published many guidance documents on how to use RWE to inform decision-making. Major initiatives such as the 21st Century Cures Act in the U.S. are making it possible to modernize trial designs and use RWE. In Europe, EMA and the European Medicines Regulatory Network established a coordination center, called the Data Analysis and Real World Interrogation Network (DARWIN EU), to provide timely and reliable evidence on the use, safety and effectiveness of medicines for human use, including vaccines, from real world healthcare databases across the European Union. These initiatives are making the use of RWE in drug development and approvals a reality.

Driven by the increased use of RWE to inform regulatory and reimbursement decisions, the bar for RWE methodologies, the type of data collected, and the criteria for acceptance of the data has been raised. Approaches to RWE must necessarily become more sophisticated, evolving to on one hand deal with the available secondary data, and on the other to design more robust studies that accurately capture needed primary data.

But one of the biggest changes to RWE is patient empowerment. In the US, patients now can access their own health records digitally, and in Europe, the European Commission is working on making that possible too. This will revolutionize how data is captured, shared, and used. Technologies such as our very own  Health Storylines™, which have been available to support patients coping with their disease, will become the epicenter of RWD, since now we can capture the patient’s interactions with the healthcare system (e.g., doctor visits, prescriptions) but we have the possibility to complement that with patient-reported outcomes (e.g., symptoms, quality of life) which are almost always missing from traditional secondary data sources.

What exciting new opportunities exist for RWE?

As mentioned earlier, the technologies that can directly talk with patients and capture patient’s own medical records are the most exciting opportunities for RWE in the recent future, especially in the US.

Another exciting field is the field of innovative clinical trial designs, which are a hybrid between traditional, highly controlled Randomized Control Trials (RCTs) and RWE, which is not controlled. These hybrid designs test the efficacy of a product in a semi-controlled manner. Patients like this approach because it’s more representative of their everyday life. Inclusion and exclusion criteria are less strict, so hybrid trials are more inclusive.

One driver of this is the growth of rare diseases, caused by research that is narrowing specific diseases to smaller populations. RWE is often used as an External Control Arm (ECA) to contextualize the results of a single arm RCT, or to better understand the disease and inform key stakeholders of what patients are suffering and what it’s like to live with a disease. Certain diseases may not be terminal but have a severe impact on Quality of Life. Payers and health authorities decide where to invest, and it’s important for them to understand what the real burden of a disease is. This can be brought to life with RWE.

An ECA can also be used to support the control group in a RCT. A study might have a very highly controlled intervention group and a smaller control arm which can be complemented with RWE. So there are many different study designs that don’t follow the parameters of a traditional RCT or observational study, and these alternatives are used more and more.

Certain regulators are more open to the use of RWE in these innovative trial designs and ECAs, others are not. Each regulator has their own criteria for how to evaluate a study, and that guidance is based on a traditional clinical trial. But overall, the use of hybrid studies to determine the efficacy of drugs is gaining traction. For example, in Germany, they will accept an ECA only if the differences between the intervention and the control is dramatic. But actually a few years ago, these criteria didn’t even exist. They weren’t even talking about external control arms. So things are changing.

What’s next for RWE in 2023 and beyond?

The next big revolution in RWE is new regulations around patient data collection and sharing. The U.S. is at the forefront, passing a new law recently giving patients access to their own electronic medical records, and a similar initiative is underway in Europe. Traditionally, data has been collected routinely through patient interactions with the healthcare system for the purpose of record keeping. Drug developers access that secondary data through healthcare institutions and healthcare professionals and leverage it to analyze outcomes. Patients passively provide that data. Now, this is a huge shift to truly putting the patient at the center of data access and sharing. This will harmonize data collection and help to more easily advance our understanding of diseases overall. Instead of relying solely on physicians to define what new treatments should be developed, or how studies should be designed to test those new treatments, we can understand what really impacts patients.

I’m happy that the leadership at Alira Health, with our mission to humanize healthcare, has invested in technologies that enable us to capture data directly from patients. With these digital health tools, we can truly understand the burdens associated with a disease and the outcomes associated with a technology. We can talk directly to patients and leverage their input across the lifecycle of a new product.

The trend that I see is that patients are happy to share their health data because it advances knowledge. We do need to clearly communicate so that they understand how their data will be used, but if that’s clear, patients are definitely willing to help for their greater good.

The other RWE revolution that’s coming is related and that is personalized healthcare. The patient data that is generated through digital health solutions can enable physicians to deliver personalized healthcare, which is really the dream. Physicians will be able to fully understand the patient they have in front of them, and will decide which therapy will work best for that person, based on their full medical history as well as their reactions and outcomes from past therapies. This will have an enormous impact on how medicine is practiced and ultimately, on patient health.

Catia, what does Alira Health bring to the table when it comes to RWE?

Our role is twofold; first is strategic support. We work with clients to think about their RWE strategy. We help them figure out how to integrate it with their other evidence generation strategies, such as clinical and commercial, and we contextualize that with their evidence requirements. At Alira Health, we put the needs of all the stakeholders – patients, payers, and physicians – into perspective, and we help our clients design RWE strategies to meet these needs.

And then the second part of our role is the operational side. We help our clients to design and execute RWE studies. We work to identify the best data sources and engage with them, and if the right data is not available anywhere, we use our digital health solutions to collect data from patients or from physicians. We analyze the data and most importantly, transform it into outputs that help advance our understanding of the disease and support the clients with their interactions with the health authorities and payers

Personally, I’m involved in the strategic side, but also on identifying new real-world data solutions. I work closely with our clients to design studies so that the outcomes can help drive access to the new technologies faster and in a more optimized manner.

This is a wonderful time to be involved with RWE; the acceptance and the use is growing rapidly and I see a great future ahead with enormous benefits to patients.