Real World Evidence (RWE) and patient reported outcomes (PROs)

Following the 2021 Review into the usage of real-world evidence (RWE) and patient reported outcomes (PROs) in the regulation of medicines and medical devices, the Therapeutic Goods Administration (TGA) has made several changes to clarify the use of RWE and PROs in our regulatory decision-making and to encourage sponsors to identify the use of RWE/RWD in their submissions to the TGA.

The changes include adoption of a definition of RWE, revisions to the Pre-submission Planning Form (PPF) for prescription medicines applications, updated Clinical evidence guidelines: Medical Devices, as well as adoption of international scientific guidelines on this topic.

These changes are in line with the outcomes from the Review and intend to assist sponsors wanting to submit RWE/PROs to the TGA and provide transparency of our usage of RWE/PROs in evaluations and regulatory decision-making of therapeutic goods. The TGA will also describe our usage of RWE and PROs in prescription medicine evaluations in Australian Public Assessment Reports (AusPARs).

Importantance of changes

The TGA already accepts RWE and PROs in premarket and post market evaluations of medicines and medical devices. However, as more and more health data accumulate in various forms and new analytical frameworks are developed, the potential for RWE usage is growing.

Definition

The TGA undertook a targeted consultation with stakeholders from industry and consumer groups on the adoption of FDA’s definition of RWE. Based on the outcome of this consultation, the TGA has adopted the following definition of RWE.

Data regarding the usage, or the potential benefits or risks, of a therapeutic good derived from sources other than traditional clinical trials.

Amendments to the Pre-submission Planning Form (PPF) for medicines

The TGA has amended the Pre-submission Planning Form (PPF) to include a RWE usage declaration for sponsors of prescription medicines applications. Sponsors are encouraged to provide information on any RWE, RWD and/or PRO included in their submission and reasons for including this data e.g., the claims these data are supporting. 

Updates to Guidelines

The TGA has revised the Clinical Evidence Guideline for Medical Devices to offer some information to sponsors regarding the use of RWE/RWD and PROs in medical device applications.

Adoption of international guidelines

Where possible, the TGA aligns its regulatory approach to that of comparable overseas regulators (CORs) and adopts international guidelines to ensure we are harmonising our data requirements, including RWE, with those of other international regulators. Following a public consultation process, the TGA has adopted the following international scientific guidelines to offer guidance to the industry on the use of RWE and RWD in regulatory submissions:

• International scientific guideline: Guideline on registry-based studies EMA/426390/2021
• International scientific guideline: Appendix 2 to the guideline on the evaluation of anticancer medicinal products in man. The use of patient-reported outcome (PRO) measures in oncology studies EMA/CHMP/292464/2014
• Submitting documents using RWD and RWE to FDA for drugs and biologics – Guidance for Industry
• Rare Diseases: Natural History Studies for Drug Development – Draft Guidance for Industry  
• Considerations for the Use of Real-World Data and Real-World Evidence To Support Regulatory Decision-Making for Drug and Biological Products – Draft Guidance for Industry
• Data Standards for Drug and Biological Product Submissions Containing Real-World Data – Draft Guidance for Industry  
• Use of Electronic Health Record Data in Clinical Investigations – Guidance for Industry

Continuing engagement with comparable overseas regulators on use of real-world evidence (RWE) and real world data (RWD)

The TGA notes the growing usage of RWE internationally and will continue to actively monitor and engage with comparable overseas regulators on developments in this area.

2021 review

We commissioned a review in 2021 into our usage of real-world evidence (RWE) and patient reported outcomes (PROs) in the regulation of medicines and medical devices. 

This considered stakeholders' understanding of what RWE and PROs are, and how we and other international regulators use them.

We use both RWE and PROs in premarket and post market evaluations, and the review found that:

• there is ambiguity (internally and externally) surrounding our usage of RWE and PROs, which potentially limits its adoption.
• stakeholders recommend that we improve our communication about how the TGA accept and use RWE and PROs.

Changes being made

From these learnings, over 2021-22 we will:

• establish a central point for information about RWE and PROs on the TGA website.
• clarify our related definitions and reduce ambiguity where we can.
• request applicants to document why and where RWE and PROs have been included in the application and their purpose for inclusion.
• begin to communicate when RWE and PROs are used in making regulatory decisions.
• consult on relevant guidance for the use of RWE and PROs as evidence for the regulation of medicines and medical devices. These will cover generation of data (for inclusion in the dossier), and utilisation in evaluating the application. This is a developing field, and we anticipate our guidance will be an agile resource for the industry.
• continue to learn from international sources (including medical and scientific literature, research, and regulatory guidance) for generation of RWE and PROs to maximise alignment with international regulator practices.
• understand how we might support the enhanced use of RWE and PROs into the future. This may include providing advice to potential applicants and designers of RWE and PROs programs intended for regulatory use, and the use of RWE and PROs for medicine regulation pathways such as orphan or provisional medicines, or for repurposing of medicines.
• encourage the adoption of medical device unique device identifiers in the broader healthcare system and specifically, in medical device registries, to support a stronger foundation for the collection of RWE and PROs.
• consider how to best implement this work in our international collaborations.

More information

• Real world evidence and patient reported outcomes in the regulatory context (pdf,206kb)
• Real World Evidence (RWE)