21st Century Cures Act and the Increasing Dependency on Real-World Data

The 21st Century Act was launched primarily for facilitating the acceleration of cancer research, and extending precision medicine to all diseases through the Precision Medicine Initiative (PMI). The Cures Act supports the US Food and Drug Administration (FDA) to streamline the process for drug and medical device approvals, promote increased use of electronic health records, and advance the implementation of telehealth services. The Cures Act facilitates advancing the medical product development and speedy delivery of medical innovations for patients in need.

Under section 505F- of the Cures Act, the FDA created a framework for evaluating the potential use of real-world evidence (RWE) to help support the approval of a new indication for a drug already approved under section 505(c) of the FD&C Act or to help support or satisfy drug post-approval study requirements. While the Cures Act enhances the scope for clinical trial designs, including the use of real-world evidence, and clinical outcome assessments, it also contributes to speeding up the development and review of novel medical products, including medical countermeasures.

The Cures Act defined the distinction between real-world data and real-world evidence identifying, RWD as the data relating to patient health status or the delivery of health care routinely collected from a variety of sources like EHRs, claims, bills, etc. It stated that RWE is the clinical evidence about the usage and potential benefits or risks of a medical product derived from the analysis of RWD.

While a traditional clinical trial is more likely to have restrictive eligibility criteria that are designed to ensure that the participants have the disease of interest, and disproportionate patient diversity into consideration, often not including patients who are old or have multiple illnesses. The RWD can supplement the trials to get a more accurate view of the patient populations comprising larger socioeconomic, racial, age, and gender diversity.

Scope of Real-World Evidence under 21st Century Cures Act

Recognizing the possibilities of using RWD and RWE, the FDA has set a strategic priority to leverage the information to enhance regulatory decision-making. Collating data from sources external to the clinical trials is extremely important to facilitate the drug approval process, as the clinical trial data, solely, do not reflect the accurate impact the drug would have on a larger patient population, given its strict inclusion and exclusion criteria.

For instance, when Pfizer announced the approval of a supplemental New Drug Application by the FDA to expand the indications for IBRANCE with an inhibitor to include men with HR+, HER2- advanced or metastatic breast cancer, it was based on the data from EHRs and postmarketing reports of the real-world use of IBRANCE.

Chris Boshoff, M.D., Ph.D., Chief Development Officer, Oncology, Pfizer Global Product Development stated, “With this approval, we are now able to offer IBRANCE to the underserved male breast cancer community and provide more patients with HR+, HER2- metastatic breast cancer the opportunity to access an innovative medicine... We appreciate that our partnership with the FDA has allowed us to take a significant step forward in the use of real-world data to bring medicines to patients who are most in need.”

Bret Miller, founder of the Male Breast Cancer Coalition applauded the use of RWD and said, “Men with breast cancer have limited treatment options, making access to medicines such as IBRANCE critically important... We applaud the use of real-world data, a new approach to drug review, to make IBRANCE available to certain men with metastatic breast cancer and help address an unmet need for these patients.”

This makes it clear that the real-world data is playing a significant role in expanding the use of already approved innovative medicines. Given the rarity of breast cancer cases in males, fewer clinical trials are conducted for the male population, resulting in fewer approved treatment options for them. In the U.S. in 2020 It was estimated that there would be around 2,620 new cases of invasive breast cancer and about 500 deaths from metastatic breast cancer in males. The 21st Century Cures Act helped accelerate medical product development, allowing innovations and advances to become available to patients who need them faster and more efficiently, with special focus being given to the use of real-world data to support regulatory decision-making.

Benefits of Deploying Real-World Data

• Greater understanding of the diverse patient journeys, treatment pathways, and levels of drug effectiveness
• Generating hypothesis for testing in randomized controlled trials
• More efficient drug development programs
• Identification of populations with heightened benefit/risk
• Minimization of the number of patients exposed to less efficacious therapy
• Augmentation of the safety contours of a drug
• Development of evidence to support expanding the indication for a drug

Most Relevant Procedural Values to Keep in Mind while Deploying RWD

• Reflexivity: The research should be conducted while keeping the conflicts of interest at bay and having a solid process in place to manage them.
• Transparency: The research processes as well as the data should be open to scrutiny, with results being published.
• Accountability: The researchers should take responsibility for their actions and be accountable to an ethics committee, data access committee, clinicians, patients, and the public, as per the laws set by the FDA.

Real-world studies can guide us towards a better understanding of how a treatment is used in everyday clinical practice, its impact, and how a treatment is prescribed by health-care providers in everyday environments, going beyond the study of the subjected human population. This helps in improving the trial designs to accelerate the drug approval process.

The significance of the real-world data has been magnified with the COVID-19 pandemic that made the world stand still for a while. The sudden spread of the disease made the information available under the restricted trials inconsistent and heterogeneous due to the limited testing capacity and disparate testing criteria. The situation called for an approach to gather information that had the potential to help the COVID-19 research in ways randomized clinical trials (RCT) could not, that was when the need for RWD was reinforced in the cure development process.