Capturing and sharing a fuller picture of a person’s health story to achieve improved health outcomes that reflect that person’s health goals is the holy grail of health data regulation. Many hurdles stand in the way from a lack of consistently adopted data standards, perverse incentives by data holders to disregard and even block data sharing, and a lack of awareness of these issues by those it affects most. In response, through the 21st Century Cures Act of 2016, legislators mandated agencies such as the Center for Medicare and Medicaid Services (CMS), the Office of the National Coordinator for Health IT (ONC), and the Federal Drug Administration (FDA) to publish regulations and guidance to address some of these issues and further the ability to seamlessly collect and exchange information vital to improving care and outcomes.

In parallel, over the last decade, many healthcare stakeholders have grown to understand the potential of exchangeable electronic health data and have begun creating efforts, such as data registries, to leverage the potential of this data. Patient advocacy organizations have begun exploring how to use their registries to create strategic partnerships with entities such as pharmaceutical and medical device companies to spearhead the creation of improved therapeutics that meet the needs of their patient communities. Though policies and data standards have matured through the Cures Act regulations under the CMS and ONC to support these patient organizations’ goals, a lack of comprehensive FDA guidance on the use of real-world evidence stalled pharma and device industries from using data beyond what was collected specifically for a clinical trial. Until now, this has created a major barrier for patient organizations to optimally leverage the real-world data they have spent years to collect. However, in 2018, the FDA worked with the ONC to finalize the first of their Cures Act guidance that outlined recommendations to the pharma industry (Industry) with the aim of raising confidence in using data from Electronic Health Records (EHR) as source data for the advancement of drugs and devices.

Recently in both late 2021 and early 2022, the FDA updated this EHR data guidance and released three additional guidances to Industry for using real-world evidence. These four FDA guidances were offered as drafts that are open for public comment. Federal agencies wholeheartedly welcome public comments from patient advocates as individuals or from patient advocacy organizations. The public comment periods for these four FDA guidances are now closed and the final versions are set to be released later in 2022. This new landscape is one of increased promise for patient organizations allowing them to make a greater impact with their patient registries. The release of these guidances so close together signals FDA deep commitment to using real-world data and evidence.

These are the four seminal draft FDA guidances and their potential impact on patient advocacy organizations.

Guidance: Real-World Data: Assessing Electronic Health Records and Medical Claims Data To Support Regulatory Decision-Making for Drug and Biological Products

Issue Date: September 2021

What this guidance covers

This guidance provides recommendations on how to appropriately design a study using data from EHRs or billing data (claims data) to submit a drug or biological product for FDA approval. FDA’s aim in this guidance is to ensure effectiveness and safety of the submitted product, on how to select relevant data sources and define and validate study variables to support regulatory decisions on effectiveness and safety. This guidance covers concepts such as choosing the right data that is relevant to the study and making sure the data can be trusted—such as proof of where the data comes from and when it was collected.

Why this guidance matters for patient advocacy organizations

The fundamental aim of this guidance is ensuring that FDA endorsed drugs or biological products lead to appropriate health outcomes without the patient also experiencing life threatening side effects. Advancing studies to use and submit EHR or claims data to the FDA instead of requiring providers to add a layer of data collection eases providers’ burden and the cost of recruiting study sites. Improved site recruitment and retention is vital to successfully advancing therapeutic development for patient communities.

Guidance: Data Standards for Drug and Biological Product Submissions Containing Real-World Data

Issue Date: October 2021

What this guidance covers

This guidance focuses specifically on the necessary data standards that industry stakeholders must comply with when submitting RWD as study data in an FDA submission used to support various FDA approval tracks. For example, the guidance requires that RWD (including data from EHRs, medical claims, registries, patient-generated data, and other sources) must be in an electronic format that the Agency can process, review and archive. In this guidance, FDA recognizes a range of approaches that may be used to transform datasets but focuses on specific standards and requires industry to document their conformance methods and their rationale for the methods they chose.

Why this guidance matters for patient advocacy organizations

Compatible data is essential to promoting the ease of sharing data electronically, otherwise known as data interoperability. Bringing data together from multiple sources provides clinicians, patients, and researchers valuable insight into the manifestation of health conditions and the effectiveness of established or experimental treatment protocols. This deeper level of insight, that takes in a fuller picture of the patient’s health story, provides all stakeholders, especially the patient, the power to make more educated decisions that reflect their desired health outcome. Without data interoperability, the feasibility of bringing data together from disparate sources to make sense of the information becomes unrealistic due to the time and cost of making the data compatible for analysis.

Guidance: Real-World Data: Assessing Registries to Support Regulatory Decision-Making for Drug and Biological Products Guidance for Industry

Issue Date: November 2021

What this guidance covers

This guidance provides industry detailed considerations when deciding whether a registry’s data is acceptable to use in their FDA approval submission for a drug or biological product. This guidance lays out attributes of a registry that support the collection of relevant and reliable data. This guidance also provides numerous considerations for linking registry data to other data sources for supplemental information, such as data from medical claims, EHRs, digital health technologies, or other registries.

Why this guidance matters for patient advocacy organizations

This guidance is the quintessential list of FDA-approved best practices against which patient organizations can model their registry builds to ensure industry partnerships and industry relevance. It shows FDA’s growing support for industry to consider patient advocacy organizations as a data source partner. However, the FDA is careful to instruct industry to be vigilant of data from registries that do not meet the minimum criteria laid out in this guidance. For example, the FDA advises industry to work with registries with data elements that are meaningful to the study at hand— “known as relevance of data,” provides information about the data that promotes trust—known as “reliability of data,” and the ability to harmoniously link a particular registry’s data with data from another system. How the FDA defines the concepts of data quality in this guidance will directly influence what types and structures of data industry will accept from patient registries.

Guidance: Considerations for the Use of Real-World Data and Real-World Evidence To Support Regulatory Decision-Making for Drug and Biological Products

Issue Date: December 2021

What this guidance covers

This guidance lays out best practices for using real-world data to help support FDA approval applications for an investigational new indication of a drug (IND) that has already been FDA approved for another use. For example, the FDA requires the documentation of all analyses performed on the data during the study design phase. The purpose of this level of documentation is to ensure that FDA inspectors have a history on and can access all the relevant data necessary to verify data integrity.

Why this guidance matters for patient advocacy organizations

This guidance strengthens the major role patient advocacy organizations can have in being the source of data for studies that support IND applications. Some of the most exciting therapeutic advances for many disease groups, including rare diseases, involve utilizing drugs and procedures already established for other diseases. Supporting the IND process with registry data can be a rewarding use of a patient advocacy organization’s data assets and open opportunities to fulfill a core mission of advancing therapeutic solutions for their patient community. Supporting the IND process also signals new heightened business and sustainability opportunities for patient advocacy organizations with strong data registries that can support the level of documentation their industry partners will need for FDA data submissions.

Conclusion

Patient advocacy organizations should note that these guidances are written to industry stakeholders that submit data to the FDA for product approval. Patient advocacy organizations need to convert these recommendations into data handling processes they must adopt to promote successful partnerships with industry. In this guidance translation process, patient organizations must weigh their goals against the regulatory pressures on industry set forth by the FDA. Patient advocacy organizations should also note that FDA guidances are closer to recommendations to industry rather than requirements set forth in official federal regulations. This means that FDA keeps the door open to public stakeholders to continue to have dialogue with the FDA on what data, data processes, and data standards would be accepted by the FDA. Patient advocacy organizations should be encouraged that the FDA has been public about their desire to see the increased use of real world data and real-world evidence, as evidenced by the FDA’s establishment of their RWE program.