Real-World Evidence: A Primer

What is real-world evidence?

Real-world evidence (RWE) is evidence about the use, safety, and effectiveness of a medical product, technology, or drug that is based on or derived from analysis of data generated in a real-world health care setting.

Real-world data (RWD) includes information about the health of individuals or the delivery and/or outcomes of health care that is collected outside of traditional clinical trials and thus reflects results within the context of the particular health care system.

Where does RWD come from?

Potential sources of RWD include:

• health care records
• registries of patients with certain diseases
• registries of patients treated with a specific drug or health technology
• electronic medical records
• public or private insurers
• wearable and other biosensor devices
• patients.

RWD can be collected by patients and patient groups, physicians and other health care providers, regulatory agencies, governments, and pharmaceutical and other private companies. The data may vary in quality and are not always fit for the purpose of informing decision-making.

How is real-world evidence generated?

Real-world evidence comes from the analysis of RWD. However, RWD can only serve as evidence for decision-making if it is considered to be relevant and reliable information.

What are randomized controlled trials?

Randomized controlled trials are often considered the gold standard method of gathering evidence about the safety and efficacy of a drug or treatment. In these types of studies, a precisely defined group of patients are enrolled and randomly assigned to either a group receiving the intervention being studied or to a control group who do not receive that intervention.

What are potential shortcomings of clinical trials?

Clinical trials may have limitations, including the following:

• They are conducted under highly controlled conditions that often do not reflect the realities of treating patients in actual practice.
• Follow-up time is often limited and prevents measurement of long-term health outcomes.
• They often do not reflect the diversity of the Canadian population and exclude or under-represent certain types of patient populations, such as pregnant women or women who are breastfeeding, children, older adults, and those with multiple chronic health conditions.

Why use real-world evidence to inform decision-making?

Real-world evidence can be used to:

• provide complementary clinical evidence on the use, benefits, and risks of medical products or technologies to fill gaps in evidence from clinical trials
• evaluate the effects of clinical interventions in specific patient populations and health care settings not included in clinical trials
• measure longer-term health and safety outcomes that may not be available from clinical trials
• measure trends in utilization of health care services and burden of diseases
• provide information about the effectiveness and efficiency of health services and program performance
• provide information on how drugs and health technologies are implemented and managed in the real-world setting.

How can real-world evidence be used in the drug approval process?

Real-world evidence has the potential to fill gaps in clinical evidence that are generated in clinical trials and can facilitate a more comprehensive assessment of the safety, efficacy, and effectiveness of drugs or health technologies to a broader population, over a longer time period, and which considers the context of the Canadian health care system.

The role of real-world evidence can be especially important to meet the challenge of assessing drugs submitted for approval to treat rare disorders. In these cases, it can be challenging to develop robust clinical evidence due to the small number of patients affected by the condition, the impracticality of conducting a randomized controlled trial, or ethical concerns.

Real-world evidence can help decision-makers determine if the conditions or scope of use for a product should be revised. It can also help determine the optimal order of drugs within a drug sequence to optimize their benefits. Finally, real-world evidence can help health care providers and patients determine whether a drug is the right choice to meet their treatment goals.

It is also important to evaluate a drug or intervention throughout its life cycle is increasingly recognized. Real-world evidence can support the ongoing assessment of a product’s effectiveness and safety within the Canadian health care setting.

For more insight on the integration of real-world data and evidence to support decision-making in the pharmaceutical sector, please see a recent State of Knowledge report from the Institut national d’excellence en santé et en services sociaux (INESSS). The report from INESSS, translated by us, provides a narrative review of the literature on the use of real-world evidence and real-world data in assessments to support the decision-making process in formulary listing drug reviews. The state of knowledge document is solely for information purposes and does not constitute a position paper or recommendations.

How is real-world evidence already being used in Canada?

Real-world evidence is currently being used in Canada to:

• fill gaps in the available evidence from clinical trials
• provide complementary data that is important to decision-makers
• monitor adverse drug reactions and evaluate the risks of a health technology after it has been approved and is being used in the real-world health care context
• inform potential changes in reimbursement criteria for drugs and other health technologies already in use in Canada
• gather information on the safety and effectiveness of drugs and other health technologies when they are used more broadly in the real-world clinical setting.

What are the challenges of using real-world evidence?

Challenges associated with using real-world evidence to inform decision-making include:

• Cause and effect cannot be determined from data collected from the real-world setting because potential biases cannot be sufficiently controlled.
• The quality of RWD can vary depending on what is being measured, the source of the information, and how the data are collected, analyzed, and reported.
• There is a lack of clear and consistent standards that define when real-world evidence is acceptable for decision-making.
• The practice of planning and generating real-world evidence requires multi-stakeholder engagement and a process to establish agreement about what RWD needs to be collected, how it will be shared between stakeholders, and how it will be used to inform decision-making.