Real-world evidence (RWE) has become a significant enabler in research to measure the benefits and risks associated with oncology treatments in development. With the growing number of rare and aggressive cancers stratified by molecular subtypes, it becomes especially important to find alternative solutions for clinical development pathways when clinical trials are not possible.
In response, RWE has emerged as a valuable complementary resource to provide information beyond what is learned from randomized clinical trials. For single-arm trials, RWE can provide comparative context for interpreting results on the safety and efficacy of medical products. RWE is also enabling researchers to extend the follow-up of patients beyond the limits of a trial with observational, “lighter-touch” periods of follow-up, which allow for longer-term assessment of
By understanding when and how to use RWE as a complement to single-arm oncology trial data, researchers can incorporate it into their evidence packages to support new oncology treatment approvals, as well as label extensions for existing products.
Optimize Your Study Design Early
Advanced planning is crucial to optimize the value of RWE for oncology studies. First, researchers should determine whether real-world data (RWD) are a valuable addition to their study design and in what capacity. All RWD must be “fit-for-purpose,” meaning they should:
• be relevant and accessible;
• have clear provenance, meaning that there is transparency in where the data came from, and how they were reviewed, curated, and assembled;
• produce actionable evidence with credible methods and study design; and
• include enough patients of interest, to be followed over a sufficient period of time, to detect an effect should one exist.
When RWE is incorporated into the clinical development process, it can contribute to faster submissions and overall development. However, coordinating the acquisition of RWE, and using it for leverage, takes careful timing and planning. Researchers should factor this time and early engagement with the regulators into their overall timelines.
Partnering With Regulators
Regulators have embraced RWE as a valuable source of information across therapeutic areas, acknowledging its capability to address important questions, such as:
In 2017, two RWE studies were used to support the accelerated approval of avelumab (Bavencio), a treatment for a rare and lethal skin cancer. Data from US electronic health records (EHRs) were analyzed to examine the eff ectiveness of standard-of-care regimens among similar patients as context to interpret results from their single-arm trial1; and in Europe, a German registry was used to provide context on the average response rates to routine treatment, duration of response, and rates of mortality among patients with this aggressive disease.2
More recently, RWE was instrumental in supporting a label expansion for palbociclib (Ibrance) to include men with advanced or metastatic breast cancer.3 The drug was previously approved for women with hormone receptor–positive (HR+)/HER2-negative locally advanced or metastatic breast cancer.
However, an analysis using claims data and an oncology patient record, which demonstrated similar benefi ts and risks among men compared with women with HR+/HER2-negative locally advanced or metastatic breast cancer, was submitted to the regulators as part of the totality of evidence to win approval for the label expansion in men.
While researchers may have historically been hesitant to make RWE a formal part of their study designs, these examples showcase how regulators are progressively evolving their stance in favor of RWE, particularly in instances when traditional trials are not possible. The key for successful utilization in oncology studies is for researchers to align with regulators on their plans to leverage these data as early as possible and provide a strong rationale for using more innovative designs.
In oncology development, engagement with the FDA may occur as part of the typical type A, type B, or end-of-phase meetings. Additionally, drug developers can request a type C meeting, which can take up to 75 days to schedule following the request. In these meetings, regulators will not provide instructions or endorsements for any particular category of RWD over another. However, they will review the study design, data sources, and analysis strategies, and offer input on whether a trial will may fall short.
Advances in technology and analytics are enabling RWD to be gathered in real time and analyzed to help make clinical, payer, policy, and regulatory decisions. The ability to quickly access data from EHRs, laboratories, pharmacies, health care insurance claims, registries, and even consumer devices provide the benefit to researchers of capturing the most up-to-date information to support their clinical trial findings.
Many of these sources, including EHRs, are largely unstructured, meaning that at least some of the data are written as a narrative with no forms or fields. For effective use of these data, study leaders should consider adopting certain tools, such as natural language processing and machine learning, that can automate translation of natural language into anonymized and structured formats. These can then be analyzed, with dependable consistency, as part of the larger data set. Digital transformation will be valuable in optimizing researchers’ time: They can focus on activities that propel studies forward rather than on manually combing through large amounts of data.
As part of the 21st Century Cures Act, signed in 2016, the FDA is expected to issue guidance in 2021 outlining, in detail, when and how pharmaceutical companies should leverage RWE to facilitate the
approval process. This guidance is expected to bring greater clarity to the process for including RWE in submissions.4 In the interim, organizations can refer to the FDA’s Real-World framework for more information about how the FDA plans to implement their RWE Program.5
The capability of RWE to create a more robust view of the benefits and risks of oncology treatments among all patients eligible for therapy is critically important. It can complement, augment, and extend our understanding of when and how to use new treatments while offering longer-term insights that can drive continued medical innovation. Organizations that adopt this approach, and plan early and effectively for it as part of their overall oncology development strategy, will be in a better position to accelerate drug approvals and label extensions for life-saving treatments.
Jennifer Christian, PharmD, PhD, is the vice president of clinical evidence and epidemiology, IQVIA, Durham, NC.
1. Cowey CL, Mahnke L, Espirito J, Helwig C, Oksen D, Bharmal M. Real-world treatment outcomes in patients with metastatic Merkel cell carcinoma treated with chemotherapy in the USA. Future Oncol.
2. Becker JC, Lorenz E, Ugruel S, et al. Evaluation of real-world treatment outcomes in patients with distant metastatic Merkel cell carcinoma following second-line chemotherapy in Europe. Oncotarget. 2017;8(45):79731-79741. doi:10.18632/oncotarget.19218
3. Wedam S, Fashoyin-Aje L,Bloomquist E,et al. FDA approval summary: palbociclib for male patients with metastatic breast cancer. Clin Cancer Res. 2020;26(6):208-212.doi:10.1158/1078-0432.CCR-19-2580
4. Real-world evidence. FDA. November 30, 2020. Accessed May 8, 2021. https://www.fda.gov/science-research/science-and-research-specialtopics/
5. Framework for FDA’s Real-World Evidence Program. FDA. December 2018. Accessed May 8, 2021. https://www.fda.gov/media/120060/download