31 AUGUST 2021 – According to a recent US FDA presentation (May 2021)[1]:

“Quality RWE can’t be Built without Quality RWD”

As noted in the National Guidelines for Data Quality in Surveys[2] published in August 2021 by the ICMR-National Institute of Medical Statistics (ICMR-NIMS)[3]:

“There is an impending need…for data quality guidelines to improve the quality of data that promotes evidence-based decision making”

In September 2020, the EMA published a [draft] checklist[4] for evaluating the suitability of registries for registry-based studies. The list is adapted from the REQueST[5] tool published by EUnetHTA[6].

Why is this important?

This is one of the first quality standards [data quality guidelines] published by the EMA that specifically addresses the quality expectations of real world data sources (i.e., disease registries) used to generate real world evidence (RWE) for regulatory purposes.

According to the EMA[7], the use of a registry-based study for a regulatory purpose depends on many factors related to its relevance to answer a specific research question, the characteristics of the concerned registry, the quality of the data collected and the design and analytical plan of the proposed study.

The tool has been developed to be a comprehensive resource that covers all important aspects relating to the quality of registries. The standards set out in the tool are universal and essential elements of good practice and evidence quality that are, therefore, relevant for different types of registries.

Examples of where registry-based studies may be useful for evidence generation[7]:

• To supplement the evidence generated in the pre-authorisation phase
• To provide data sources or infrastructure for post-authorisation evidence generation
• To evaluate the effects of medications received during pregnancy

Things to assess, be aware of, or consider when assessing the suitability of a patient registry for a registry-based study, include:

1. Administrative information
1.1. Governance for collaborations
– Publicly available documentation (with website) of key registry characteristics
– Single contact point for information
– Publicly available policy for collaborations with external organisations
– Governance structure for decision-making on requests for collaboration
– Supportive scientific and technical function
– Supportive function for ethical and legal aspects
– Template for research contracts between the registry and external organisations
1.2. Data privacy
– Status of implementation of GDPR
– Informed consent form and its validity for registry-based studies (or need for re-consent)
1.3. Funding
– Funding sources and impact on short, long-term sustainability and possible conflicts of interest for a specific registry-based study
2. Methods
2.1. Objectives
Purpose of the data collection system, which may influence the main characteristics of the registry population and the data collected
2.2. Data providers
– Adequate description of data providers, such as patients, carers or health care professionals (with different specialties), their geographical area and any selection process (inclusion and exclusion criteria) that may be applied for their acceptance as data providers
2.3. Patient population covered
– Adequate description of the type of patient registry (disease, condition, time period covered, procedure), which defines the criteria for patient eligibility
– Relevance of setting and catchment area
– Clarity on patients’ inclusion and exclusion criteria
– Methods applied to minimise selection bias and loss to follow-up
– Numbers of patients available in the registry (total number and number of eligible patients if applicable), numbers of new patients entering the registry per year, numbers of patients lost per year (with reasons for exit)
– Mean/median duration of follow-up per patient, person-time of exposure in defined categories, if applicable
2.4. Data elements
– Core data set collected from patients by all centres; optional data set
– Definition, dictionary and format of data elements
– Standards and terminologies applied
– Capabilities and plans for amendments of data elements
2.5. Infrastructure
– Systems for data collection, recording and reporting, including timelines
– Capability (and experience) for expedited reporting and evaluation (at physician or registry level) of severe suspected adverse reactions in primary data collection
– Capability (and experience) for periodic reporting of clinical outcomes and adverse events reported by physicians, at individual-patient level and aggregated data level
– Capability (and experience) for data cleaning, extraction, transformation and analysis
– Capability (and experience) for data transfer to external organisations
– Capabilities for amendment of safety reporting processes
2.6. Quality requirements
– Processes in place for quality planning, control, assurance and improvement
– Data verification (method and frequency of verification)
– Missing data (statistics, trends, variables affected, management)
– Auditing practice

What’s Next?

The 2021-2023 HMA-EMA joint Big Data Steering Group (BDSG) have published their ‘2021 – 2023 Workplan’.

Milestones to be aware of, include:

• Publication of Registries Guidance (November 2021)
• Roadmap for RWE Guidance Agreed (April 2022)
• EMA Draft Q&A on Secondary Use of Health Care Data and Data Protection (December 2021)

References

1. The FDA Real-World Evidence (RWE) Framework and Considerations for Use in Regulatory Decision-Making. Jacqueline Corrigan-Curay, JD, MD. Meeting of the Pediatric Oncology Subcommittee of the Oncologic Drugs Advisory Committee May 12, 2021
Link: https://www.fda.gov/media/148543/download

2. ICMR-National Institute of Medical Statistics (ICMR-NIMS)
Link: http://icmr-nims.nic.in/

3. National Guidelines for Data Quality in Surveys. ICMR-National Institute of Medical Statistics, New Delhi. July 2021
Link: https://main.icmr.nic.in/sites/default/files/upload_documents/National_Guidelines_for_DATA_QUALITY_in_Surveys.pdf

4. Appendix 3 of [DRAFT] EMA Guideline on Registry-Based Studies (EMA/502388/2020) (24 September 2020)
Link: https://www.ema.europa.eu/en/documents/scientific-guideline/guideline-registry-based-studies_en.pdf

5. REQueST = Registry Evaluation and Quality Standards Tool (REQueST)
Link: https://www.eunethta.eu/request-tool-and-its-vision-paper/

6. EUnetHTA – European Network for Health Technology Assessment
Link: https://www.eunethta.eu/

7. Section 3.1 of [DRAFT] EMA Guideline on Registry-Based Studies (EMA/502388/2020) (24 September 2020)
Link: https://www.ema.europa.eu/en/documents/scientific-guideline/guideline-registry-based-studies_en.pdf

8. Section 1 of the [DRAFT] EMA Guideline on Registry-Based Studies (EMA/502388/2020) (24 September 2020)
Link: https://www.ema.europa.eu/en/documents/scientific-guideline/guideline-registry-based-studies_en.pdf