Policies, Pressures and Practice Patterns:
Long-Term Evaluation Needed

May 25, 2021

In 2016, the 21st Century Cures Act (Cures Act)  directed the Food and Drug Administration (FDA) to accept statistical methods that include Real-World Data (RWD) and Real-World Evidence (RWE). The next year, the Center for Devices and Radiological Health (CDRH) and Center for Biologics Evaluation and Research (CBER) issued guidance regarding the submission of RWD and RWE to the FDA.

The Role of RWD and RWE

Both RWD and RWE have important roles as defined by the legislation to:

1. Monitor post-market safety and adverse events that result in regulatory decisions

2. Expedite approval of innovative therapeutic approaches, RWD and RWE support clinical trial designs, including approval of new indications for approved drugs

3. Develop therapeutic guidelines and decision support tools for clinical practice

4. Support healthcare insurance coverage decisions

Sources of RWD

RWD may come from various government and commercial sources including:

  • Electronic health records
  • Claims databases
  • Billings databases
  • Registries: product and disease
  • Patient-generated data
  • Health status data from mobile devices

To mitigate potential bias, the use of RWD requires a careful study design, protocol, and analysis plan that is comparable to a more traditional investigation, like a randomized controlled clinical trial, with strict inclusion/exclusion criteria and clinical endpoints.

Control Arms 

There are some challenges with prospective, randomized, controlled clinical trials. Two major drawbacks:

1. Large numbers of patients are required to conduct the study

2. Slow patient accrual; strict patient eligibility

Study needs, research ideas and business strategy including synthetic control arms, also known as historical control arms or external control arms, are important to consider. 

This type of control arm is defined as a group of patients treated at an earlier time (historical control) or a group treated during the same time period, in another setting. 

Emergence of RWD and RWE provides new opportunities to efficiently conduct large-scale studies that have many of the benefits of randomized controlled clinical trials, while being generalizable to broad populations. 

Discovering and analyzing RWD provides information regarding the clinical outcomes associated with a therapeutic approach. These outcomes, from a wide range of study designs, generate RWE.

When RWE is submitted to the FDA, both the RWD and RWE must conform to recognized data standards for file formats and data structures, using standardized variables and definitions.

Advantages and Outcomes

Historical or external control arms overcome many barriers to the completion of clinical trials, and provide a representative, rather than a highly selected, patient population in randomized controlled trials. 

In cancer trials, there are many advantages including patient access to therapeutic breakthroughs. 

Watch this video to learn more about this important topic

Medical paradigms are changing. Inefficiencies when conducting clinical trials are being addressed. Therapeutics are no longer siloed by medical subspecialty. Long recognized risks for development of disease are better understood by interconnecting biological pathways.

Outcomes are more than survival; they now also reflect the importance of controlling symptoms of disease and treatment. Greater emphasis is placed on outcomes beyond the clinical trial and in real world populations. Outcomes within real-world experiences reflect both the personal and societal cost of disease.


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As real-world evidence authorities, STATinMED Research discovers data, develops insights and delivers optimal solutions to help life science companies realize maximum value. 

Many thanks again to you and the entire STATinMED Research team for your help with the cohort comparison and timeline. It means a lot to us.

— Oncology Global Patient Outcomes Executive Real World Evidence at global biopharmaceutical company

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