Lucinda Orsini, D.P.M., M.P.H., has decades of experience working with biopharma, regulators, and health technology assessment (HTA) bodies on real-world evidence (RWE) and health economics and outcomes research (HEOR) initiatives. Over the course of her career, she has earned a medical degree, worked in the health care data analytics space, and advanced HEOR initiatives during 12 years in global HEOR at Bristol-Myers Squibb.

Now, as Associate Chief Science Officer for the Professional Society for Health Economics and Outcomes Research (ISPOR), she works with ISPOR’s members on strategic research initiatives, many of which are focused on navigating the opportunities and challenges of working with RWE.

Dr. Orsini says that among ISPOR’s regulator, health technology assessment (HTA), payer, and payer stakeholder members, “standard development around the use of RWE is a top priority.” We sat down with Dr. Orsini to discuss the use of RWE across biopharma and decision-making bodies, as well as ISPOR’s work to advance RWE methods and education. Read on as she shares perspectives on the future of RWE research in the era of COVID-19, and what opportunities exist in the work to come.

Responses have been edited for clarity and length.

Q: How did you use RWE during your time in biopharma? Where do you see additional opportunities for biopharma to leverage RWE?
A:
As outcomes researchers, we've been using real-world evidence for a long time, as have our brothers and sisters in the epidemiology space. We’re like two sides of the same coin trying to understand how health care is delivered, how products are being used, and what the benefits and risks are for treatments. 

During my time in pharma, we evaluated how a new product would fit into the current cadre of treatments available to patients in a specific disease area, as well as the unmet medical need within those areas. As time went on, and especially in the oncology space, we would use phase II data as a single-arm comparator to historical data to assess how a new treatment would compare to the standard of care. While it’s not true comparative evidence, it certainly gives you a feeling for how well a patient might or might not do depending on the treatment they receive.

Over time, stakeholders—regulators in particular—gained a better understanding of the opportunities and challenges of using real-world evidence. But it didn’t happen all at once; it was certainly a continuum with how we were using RWE at the pharma level.

There is a lot of opportunity for RWE in the regulatory space, especially now where you need data to help guide decision-making for COVID-19. We will increasingly see regulators, HTA bodies, and payers looking to real-world data to support decisions, and to revisit decisions over time as more data becomes available. Are there different patients that are benefitting now than at the time of approval? Has a new safety profile come up? I see that as the next “wave” for the use of RWE.

Q: What is ISPOR’s Transparency Initiative, and how does it aim to advance RWE?
A:
The Transparency Initiative was an outgrowth of the joint task force between ISPOR and the International Society for Pharmacoepidemiology. We brainstormed with our members about how ISPOR could help advance real-world evidence, and decided that we could help researchers be more aware of how to be transparent with their study designs and analysis plans. Certainly, transparency does not equate to study quality, but it allows the end user to dig deep into how and why the study was designed a certain way, and how the design may affect the results. With this information, the end user can make their own qualified judgment about the research and results, and contextualize them for their own analyses. 

For example, when using retrospective or secondary data, it’s especially important to register study protocols and analysis plans on a public site prior to conducting the analysis. The data used—usually electronic health record or insurance claims data—was collected for a purpose unrelated to the research question, and it’s being repurposed to understand a hypothesis or objective. It’s important to be clear about what you're doing with that data before you get too deep in the analysis due to concerns that researchers can mold the analysis to point to a desired result.

Q: What’s the next hurdle ISPOR hopes to clear to support the expanded use of RWE?
A:
When we started our RWE work, we focused on study designs and analysis plans. But it’s clear now that we need more transparency around the underlying data and its quality, collection, and provenance—an issue that was recently in the headlines with the retraction of the observational study using Surgisphere data in the Lancet and the New England Journal of Medicine. We need to determine what has to be reported in the data, and how researchers can work with the data while ensuring that the data source owners feel comfortable that they haven’t revealed too much regarding their intellectual property.

We’ve also realized we need to do a better job at communicating and educating around the good RWE methods and practices that already exist, and how we can use RWE alongside clinical trials. There's been some misunderstanding that real-world evidence can completely replace clinical trials, which has never been the intention; you need both types of information when compiling evidence. It’s important that we educate journal editors, peer reviewers, the press, patients, and decision makers so they understand how powerful these data can be, but also where the limitations are and when to use clinical trial evidence in tandem.

Q: What opportunities and challenges exist for payers and HTAs in using RWE for value assessments?
A:
Especially with innovative treatments in oncology or rare diseases, HTAs and payers are working with available data to understand as much about products as possible and decrease uncertainty around approving them at certain price points. But this data is often scarce, given challenges with running larger trials on these populations. HTAs and payers have to think about coverage with evidence development. They can make a decision now, but that’s not the final decision; they continue to work with manufacturers over time to collect additional data about a patient or population, and establish an evergreen assessment process.

In the U.S., COVID-19 has brought this to the fore, because the government has mandated that any testing, treatment, or future therapeutics must be covered, and often without any sort of patient copay. The coverage decision has been made, but how do you then assess how to appropriately use the interventions going forward? We have to figure out how HTAs and payers can be impactful as we look ahead to the use of COVID-19 interventions in the real world. And the only way to do that is by collecting real-world evidence and reassessing over time.

One of the challenges with real-world evidence is there isn’t much of it until a product actually hits the market and is used in the clinical setting. But there is still some opportunity for RWE before and at launch: you can use it to understand cost drivers for patients, or where safety issues or efficacy benefits exist for current therapies. These will feed into models used going forward, especially if other treatments exist that were not used as a comparator within the clinical trial for the new product.

Q: What opportunities and challenges exist for regulators in using RWE to inform their decisions?
A:
Regulators have been using real-world data for a long time to assess safety, with the Sentinel Project, for example. Post-approval safety studies are often required of new products, because the number of patients in a clinical trial is much smaller than the population using a product in the clinical setting, there may be safety signals that you just can’t see. Using RWE in this application was low-hanging fruit, and something that regulators are already comfortable with.

There are challenges, of course, in making sure that the underlying data are high quality, and that they are analyzed appropriately. But I think regulators would approach real-world data studies in the same way that they do a clinical trial: you have to discuss the study plans in advance, including the data source and how it will be analyzed, then run the analysis and check back in over time to align on methods and plans.

In the COVID space, we’ve seen that there are more opportunities for real-world evidence than we thought. Once there’s an Emergency Use Authorization for a product, we can start collecting data to see if the sensitivity and specificity is what we expected. We can reevaluate based on how the treatment is working in the real world. We’ve seen this with products originally indicated for other things, like hydroxychloroquine for malaria.

Q: How will RWE continue to support decisions in the future, in HEOR and beyond?
A:
We have a learning health care system. People are trying to figure out how to navigate cost and time constraints, and how to learn from the data they have on how patients are treated in real time so they can deliver the best care. They understand that clinical trials can only tell you so much, and that you always need more information.

You might have to collect additional information and revisit decisions over time to make sure a treatment is really working for your patients, and the best way to do that is with a broad understanding of your patient population and of the data specific to them. We must make use of all the available data in order to do this effectively.