Real-World Evidence – The time is now

Nordic Life Science asked the newly formed company NordicRWE about the potential of Real-World Evidence in drug development and how we can better enable Nordic health data to be transformative and a frontrunner in this field.

The amount of health-related data is rapidly increasing. At the same time, the healthcare sector is facing major challenges: it must be cost-efficient and benefit patients better. Clinical researchers are now turning more frequently to what is known as Real-World Evidence (RWE) to complement data generated from randomized controlled trials.

Real-World Evidence (RWE) is derived from the analysis of Real-World Data (RWD), which is patient and health data that comes from an array of sources, but not from conventional clinical trials. These sources could be electronic health records, disease registries, patient-generated data (including in home-use settings), and data gathered from other sources that can inform on health status, such as mobile devices. RWE, in short, is the insights that are generated when this data is analyzed.

“In combination with clinical trials, real-world evidence helps to build a “bigger picture” of the effectiveness of a medicine or vaccine is in the real-world setting.”

Creating RWE requires a combination of high-powered analytics, a validated approach and a robust knowledge of available RWD sources. If done correctly, it can provide a holistic view of patients that in many cases cannot be studied through traditional clinical trials. Since clinical trials are controlled they might not always provide the full picture about what happens when a drug is used in real life, because there are different individual conditions and prerequisites in a patient’s life that can play a big role. RWE provides healthcare, researchers and decision makers with additional information about the patient’s experience and insight into important questions about the advantages and the risks with different drugs in a clinical practices, surgical procedures or other health measures, as well as the costs for these. The life science community can also better design and conduct clinical trials and other healthcare studies. In combination with clinical trials, real-world evidence helps to build a “bigger picture” of the effectiveness of a medicine or vaccine is in the real-world setting.

”If successful, this will give patients earlier access to new treatments and overall a more rational drug utilization.”

”RWE can give crucial insight into different steps in the drug development cycle and give evidence that accelerates development, approvals and access as well as benefit/risk surveillance,” says Ketil Widerberg, Chairman of NordicRWE. ”If successful, this will give patients earlier access to new treatments and overall a more rational drug utilization.”

Aiming to set a new standard

This is also the aim of the newly formed company, NordicRWE. The Norwegian company was recently granted 16 million NOK by the Research Council of Norway for an R&D project that will focus on applying RWE during different steps in the drug development process – in accordance with regulatory demands.

”We aim to set a new standard for RWE based on observational data, by showing that our methods can give solid, well-understood and reproducible results that are accepted as regulatory-grade evidence. We are currently hiring and are looking for partners to develop our platform globally,” describes Ketil Widerberg.

NordicRWE has the ambition to be at the forefront of the data-driven drug development process, adds Christian Jonasson, board member of NordicRWE and co-affiliated senior researcher at the Norwegian University of Science and Technology (NTNU). He joins NordicRWE from the position as Specialist Director Health Data at the Norwegian Institute of Public Health.

”Our R&D efforts will focus on two areas where we can exploit the unique health data infrastructure in the Nordics. The first area is constructing regulatory-grade external control arms (ECA) for oncology trial programs. The second focus area is signal detection approaches for various problems and opportunities in drug R&D,” he describes.

Christian Jonasson, NordicRWE, hopes that there will be more public investment in the entire infrastructure of RWD in the Nordic. Photo: Gorm K. Gaare. Right image: Coronavirus. Credit: NIAID

The company will use observational data, epidemiological research methodology, and also AI and machine learning. In the first steps, the company will construct ECAs for oncology clinical trials and combine machine learning with pharmacoepidemiology for drug signal detection. Pharmacoepidemiology is the study of the utilization and effectiveness of drugs in large numbers of people and it provides an estimate of the probability of beneficial effects of a drug in a population and the probability of adverse effects. In this project, the company has partnered with the AI drug development division in NEC Corporation, the Cancer Registry of Norway, and the University of Oslo.

The company’s current product is an Epi-dashboard, developed from standing cohorts of merged RWD for different therapeutic areas. This product is used to gain new and timely insights about the patient journey, new therapeutic areas or markets, to enhance documentation for market access purposes and to guide decisions for the pipeline today.

“Our RWE products can lead to early access to new innovative drugs, but also ways to remove ineffective drugs from the market. Thus, RWE-driven decision-making can lead to more proper use of medicines that help balance both benefit/risk and cost/benefit.”

Successful outcomes for the research programs will pave the way for revenue and expansion, Jonasson continues. ”In parallel, we will also support pharma companies in delivering high-quality RWE projects that support regulatory and payer decision-making and safety and effectiveness surveillance. NordicRWE is also for the benefit of patients and society and for contributing to a cost-effective health system. Our RWE products can lead to early access to new innovative drugs, but also ways to remove ineffective drugs from the market. Thus, RWE-driven decision-making can lead to more proper use of medicines that help balance both benefit/risk and cost/benefit.”

When it comes to regulatory demands, Christian Jonasson believes that the regulators have tried to keep up with the developments. ”The rise of precision medicine, and the rapid growth of digitalization of the health care sector, have given a further impetus to RWE. Regulators including FDA and EMA have responded to this changing landscape and issued guidance documents for drug developers on how to apply RWE in different steps in the drug development process,” he says.

As observational data is more prone to confounding biases than randomized controlled trials (RCTs), reaching solid and reproducible results from RWE is not always an easy task to accomplish, he continues. ”Unsolved challenges associated with e.g. data quality, statistical methodology and transparency need to be addressed. RCT will continue to be the gold standard, but RWE can be used more to complement the evidence from RCTs and be an important instrument to contextualize results from highly-selected clinical studies. Furthermore, health data for continuous monitoring of benefit/risk and cost/benefit will be crucial. For that we need to improve data velocity in Nordic health data, working towards the goal of real-time data.”

Ketil Widerberg. Photo: Gorm K. Gaare

A treasure trove for research and innovation

The timing is now for RWE, believes Ketil and his colleagues. ”The precision medicine revolution is changing the development and use of drugs. Finding the right information in a timely manner is critical for pharma companies to speed up the time to market,” he explains. ”Today it is costly, time-consuming and difficult to get access to high-quality data and analytic solutions that can be trusted. However, technology advancements and regulatory innovation make understanding and documentation from RWE possible for new drug development projects.”

“Nordic health data, with its long follow-ups, provides incomparable completeness and extensive linking possibilities that are among the best in the world.”

The Nordics also have a great opportunity to become and maintain a leadership role in this field. Nordic health data, with its long follow-ups, provides incomparable completeness and extensive linking possibilities that are among the best in the world, notes Widerberg. ”Investments in collaboration on health data from both public and private sources have increased significantly in recent years and are crucial to position the Nordics in the forthcoming evolution of the RWE supported drug R&D process,” he says. ”The data series other countries and regions in the world need to collect, we already have available in the Nordics.”

“The reasons why the health data infrastructure overall is under-utilized relates to factors of complicated approval processes, outdated technical infrastructures and a legal framework that is hard to navigate for user groups.”

The Nordic health data infrastructure truly represents a treasure trove for public and private sector research and innovation, according to Christian Jonasson. This infrastructure is surely already today contributing to good research, some of it at the international forefront, he says. ”But, I would still say that the untapped potential is huge. The reasons why the health data infrastructure overall is under-utilized relates to factors of complicated approval processes, outdated technical infrastructures and a legal framework that is hard to navigate for user groups.”

Luckily, all Nordic countries have national initiatives underway to modernize the technical, organizational and legal framework. One-stop-shop concepts like the Norwegian Health Analytics Platform (HAP) has great potential, says Jonasson. ”Hopefully, the national initiatives we see unfold can be an important step to a more integrated Nordic and European system for secondary use of health data. The Nordic Commons and the Towards the European Health Data Space (TEHDaS) are important projects that hopefully will facilitate cross-border collaborations in the future.”

Ketil Widerberg and Christian Jonasson. Photo: Gorm K. Gaare

COVID-19 has accelerated the use of RWE

RWE has also been in the spotlight during the ongoing COVID-19 pandemic. It has been vital in helping governments, healthcare providers and communities understand how effective vaccines are at reducing the burden of, and protecting against, COVID-19, states AstraZeneca.

”RWE can help us understand vaccine effectiveness against different disease severities – from reducing deaths and hospital admissions to preventing milder forms of the disease, in reducing rates of infection across the population, in preventing transmission and spread of the virus, in different populations, including age, race, ethnicity and those living with underlying health conditions, such as asthma, diabetes and HIV,” the pharma company states.

As an example, in July 2021, Pfizer and BioNTech used an Israeli RWE study to determine immunity following the first two doses of their vaccine. The companies cited the findings in discussions around whether a third “booster” dose is needed to ensure efficacy. Also, in a study published in the Medical Journal of Australia in May this year, researchers were able to show that Pfizer/BioNTech, Moderna and Oxford/AstraZeneca vaccines appeared to reduce people’s chances of infection and hospitalization by more than 80% – regardless of their age. Researchers in Israel, Sweden, the U.S., England and Scotland analyzed multiple linked health datasets to measure effectiveness of the vaccines being deployed in their communities. They used different techniques to adjust for factors that likely confound the relationship between vaccination and COVID-19 complications.

”RWD has been instrumental in the handling of the outbreak and as a basis of informed decision-making, for instance to monitor the safety and effectiveness of the vaccines, to monitor to burden of the outbreak on the healthcare system and to follow the adherence to recommendation on social distancing in the population.”

Christian Jonasson definitely believe that the pandemic has accelerated developments and the use of RWE. ”RWD has been instrumental in the handling of the outbreak and as a basis of informed decision-making, for instance to monitor the safety and effectiveness of the vaccines, to monitor to burden of the outbreak on the healthcare system and to follow the adherence to recommendation on social distancing in the population,” he says.

In contrast, the pandemic has also clearly shown the lack of real-time data in today’s system, he adds.

”In the post-pandemic evaluation of the pandemic, my hope is that there will be more public investment in the entire infrastructure of real-world data in the Nordic,” concludes Jonasson.

The team behind NordicRWE. Photo: Gorm K. Gaare