Real-World Data/Evidence – increasing use in Healthcare for Regulatory Decision Making

Real-World Data/Evidence – increasing use in Healthcare for Regulatory Decision Making

Published on April 29, 2022

Real-World Data/Evidence – Increasing use in Healthcare for Regulatory Decision Making

What is Real-World Evidence/Data?

The availability of real world data (RWD) has been increasing steadily worldwide. These data provide an alternate source of information that can be leveraged to produce evidence of drug safety, efficacy and effectiveness across the product life cycle (1).

To inform market authorization decisions, prospectively planned clinical trials have been and continue to be considered the most robust tool for providing evidence of drug safety and efficacy. While following specific patient populations in a highly specialized environment facilitate the collection of high quality controlled data, it can limit the generalizability in real world settings (1). Patients in RCTs are highly selected and may not reflect the target population in whom the drug may be used. Actual recipients in routine clinical practice present with various comorbidities, co-medications, genetic profiles, behaviours, and perspectives. Long-term effects of drugs are also difficult to assess in RCTs designed to show efficacy in a narrow time window (2).

Moreover, conducting clinical trials is not always feasible and thus may not always be deemed ethical for certain diseases/disorders (such as rare diseases) or patient populations, where excessive trial costs or small available patient populations may introduce constraints. Expanding data and evidence sources to include RWD/real-world evidence (RWE) may address some of these concerns, and offer new opportunities to gain insight on public health, advance health care, and increase both the extent and rate of drug access for patient populations (1). RWE may also provide supportive data that has greater external validity, as well as providing information on subpopulations (ex: children, seniors, and pregnant women), off-label use, misuse, adherence, and to validate surrogate outcomes (2).

RWD is an umbrella term for data regarding the effects of health interventions (e.g., safety, effectiveness, resource use, etc.) that are not collected in the context of highly controlled RCT's. Instead, RWD can either be primary research data collected in a manner, which reflects how interventions would be used in routine clinical practice or secondary research data derived from routinely collected data. Data collected include, but are not limited to, clinical and economic outcomes, patient-reported outcomes (PRO) and health-related quality of life (HRQoL) (2). RWD can come from a number of sources, for example (2,3):

  • Electronic health records (EHRs)
  • Claims and billing activities
  • Medical chart reviews
  • Product and disease registries
  • Patient-generated data including in home-use settings
  • Data gathered from other sources that can inform on health status, such as home medical devices and wearable technologies
  • Observational studies (e.g., cohort, case-control, or case series)
  • Pragmatic studies (also known as practical clinical trials), where patients may be randomized to treatments but subsequent care and follow-up more closely resembles standard clinical practice than in a conventional RCT

Real-world evidence is the clinical evidence regarding the usage and potential benefits or risks of a medical product derived from analysis of RWD. RWE can be generated by different study designs or analyses, including but not limited to, randomized trials, including large simple trials, pragmatic trials, and observational studies (prospective and/or retrospective) (3).

Why is this happening now?

The use of computers, mobile devices, wearables and other biosensors to gather and store huge amounts of health-related data has been rapidly accelerating. This data holds potential to allow us to better design and conduct clinical trials and studies in the health care setting to answer questions previously though infeasible. In addition, with the development of sophisticated, new analytical capabilities, we are better able to analyse these data and apply the results of our analyses to medical product development and approval (3).

All regulatory agencies accept RWD to supplement clinical trial data on the safety of pharmaceuticals (both pre- and post-approval), and real-world studies may be conducted in order to meet post-authorization data requirements requested by regulators. The FDA and the European Medicines Agency (EMA) have developed accelerated or conditional approval mechanisms, whereby drugs may be approved based on phase II studies or surrogate outcomes, with subsequent evidence to be developed that confirms efficacy and safety (2).

Where does Health Canada stand in this process?

Health Canada already considers RWE during the pre- and post-market drug regulatory process to inform decision-making and its expertise in this area continues to evolve (1). It accepts all relevant data in support of a drug’s efficacy and safety, including RWD, with no limits by study design or data source (2). There are several existing guidelines that can be used to characterize the quality of evidence in real world studies. To date, no specific guideline has been identified for implementation by Health Canada (1).

Health Canada and the Canadian Agency for Drugs and Technologies in Health (CADTH) recently announced their intent to co-develop an action plan to optimize the process for the systematic use and integration of RWE into both regulatory and reimbursement decision-making in Canada. When implemented, this will have a significant impact on how drugs are approved and paid for in Canada (4). The Health Canada project on ‘Strengthening the use of RWE for Drugs’ is an initiative under the Regulatory Review of Drugs and Devices, which aims to improve Canada’s ability to better leverage RWE throughout the drug product life cycle to optimize safety and efficacy, and overall, improve the accessibility, affordability and appropriate use of drugs (1).

Health Canada offers sponsors 15 key elements in the document, Elements of Real World Data/Evidence Quality throughout the Prescription Drug Product Life Cycle that should be considered for each research protocol, including data management and quality control, and ethical and data protection issues (1). Health Canada also provides the requirements in the document, Optimizing the Use of Real World Evidence to Inform Regulatory Decision-Making that sponsors filing a drug submission with Health Canada containing RWE as pivotal evidence are required to follow (5). 

Regulatory bodies are exploring ways that RWE could play a larger role in initial market access decisions, extension of indications, or in situations where there is considerable unmet need. There is also interest in how RWE can support or satisfy post-approval study requirements. As more information on the impact of RWE on drug marketing approval and reimbursement becomes available, the place of RWE in single-drug assessments will become more clear, which may be translated into the development of new processes and standards across the globe (2).

Author: Pratibha Duggal, ICON Plc.


  1. Health Canada Guidance Document: Elements of Real World Data/Evidence Quality throughout the Prescription Drug Product Life Cycle 
  2. CADTH Use of Real-World Evidence in Single-Drug Assessments Environmental Scan 
  3. FDA Guidance Document: Real-world data (RWD) and real-world evidence (RWE) are playing an increasing role in health care decisions 
  4. Tadrous M, Ahuja T, Ghosh B, Kropp R. Developing a Canadian real-world evidence action plan across the drug life cycle. Healthcare Policy. 2020 May;15(4):42.
  5. Health Canada Notice: Optimizing the Use of Real World Evidence to Inform Regulatory Decision-Making 

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