written by Julie Carter, MPH
I recently had the pleasure of serving on a panel discussion as part of a webinar titled HEOR & RWE: Global Sourcing Strategies and Best Practices. Other panelists included Patti Peeples, RPh, PhD, CEO HealthEconomics.Com and Mary Beth Ritchey, PhD, Director, Epidemiology, Medical Devices & Real World Evidence, RTI Health Solutions. As the discussion moved to the Q&A portion, the main topic the audience wanted to hear more about was regulatory trends. Basically, as research organizations continue to conduct more RWE studies and utilize more real-world data (RWD), what changes can we expect to see from regulatory agencies?
Firstly, let’s discuss what regulatory activities currently take place around RWE. Since RWE is not new, regulatory agencies have been using it to continually monitor the safety of products once approved in the market. Monitoring comes in the form of post marketing authorization studies, post authorization safety studies, risk management plans, etc., which are important factors in a product’s value story and risk benefit profile. But the question remains, can RWE be utilized even more in the regulatory approval process, and if so… what can we expect?
RWE has been accepted as evidence for medical devices (in the US) and in Europe for drugs, but only recently has the FDA released the RWE Framework that will pave the way for the use of RWE to gain approval for pharmaceuticals in the US.
The Process to Receive Approval for Market Entry
In order for a new product to receive approval for market entry, evidence from randomized clinical trials (RCT) must be submitted to the local regulatory body to ensure that the product is safe, effective and necessary for use by patients. If a product is already commercially available in one country, and the company wants to revise the labeling or enter a new market, does the company still need to provide the justification from an RCT? Or, can the manufacturer leverage evidence that has already been collected and is just sitting there, waiting to be analyzed? Clinical trials can be long, expensive and not representative of the general population – leaving opportunity and reason to use RWE in a complementary fashion. Here are two examples:
- In 2011, the FDA approved a novel treatment for trans-catheter aortic valve replacement (TAVR). The organization receiving the approval collected Real World Data (RWD) from a registry database and was able to analyze the off-label use of the procedure. Since enough supporting evidence was collected on the off-label use, the company was able to receive additional approval for a new treatment using the results from the RWE study. (1)
- Roche received FDA approval to market a lung cancer therapy in the US but received conditional approval in the EU and was required to provide additional evidence towards the efficacy of the product. In order to meet these obligations, Roche worked with Flatiron Health to provide evidence through RWD in addition to conducting a Phase III RCT. The RWE portion included a retrospective analysis of electronic health records, which provided enough evidence to gain approval from several European health technology assessments (HTAs) prior to the completion of the Phase III RCT. (2)
Both case studies led to compiling evidence faster, quicker regulatory approval and achieved cost savings – proving RWE has the potential to bring products to patients faster than waiting for evidence from a RCT. That being said, the data source needs to be of high quality. The reason the two use cases above were able to receive approval was due to the completeness of the data. Remember, regulatory bodies will still need to inspect the data for safety, function and improvement of health outcomes. RWE has disadvantages with confounding, while RCT is designed to inhibit confounders in order to prove the treatment is the cause of a beneficial outcome.
In short, RWE usage is here and will only continue to grow, especially since the FDA released the new framework and guidance for RWE utilization in the regulatory approval process. This is the biggest reason RWE will grow in the future, followed by the explosion of the data sources. RWE is not meant to replace RCT; RWE is meant to complement RCT or even address the pitfalls of time and cost. Using robust data sources to complement clinical trials will provide superior results for the patient. Leveraging smart study designs, answering important research gaps and working collaboratively with suppliers to conduct RWE studies is a successful strategy in this space.
To read more on this subject and other RWE & HEOR-related findings, download the exclusive white paper, HEOR and RWE Sourcing and Procurement Challenges and Opportunities: A Benchmarking Survey. A collaborative effort between Scientist.com and HealthEconomics.com, the white paper delivers survey results from stakeholders within pharma, biotech and CRO services regarding challenges in outsourcing HEOR and RWE.
- Shuren, J. & B. Zuckman. (2017) “How Creative FDA Regulation Let to First-in-the-World Approval of a Cutting-Edge Heart Valve.” Available at: https://www.massdevice.com/creative-fda-regulation-led-first-world-approval-cutting-edge-heart-valve/
- Chatterjee, A. et al. (2018) “Real-World Evidence: Driving a New Drug Development Paradigm in Oncology.” McKinsey & Company. Available at: https://www.mckinsey.com/industries/pharmaceuticals-and-medical-products/our-insights/real-world-evidence-driving-a-new-drug-development-paradigm-in-oncology