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Real World Evidence (RWE) 201 – EU – EMA Big Data Steering Group Updates Its Workplan to Accelerate Transformation to Data-Driven Medicines Regulation

RWE 201 – EU – EMA Big Data Steering Group Updates Its Workplan to Accelerate Transformation to Data-Driven Medicines Regulation

Updated EMA Big Data Steering Group Workplan:

The Heads of Medicines Agencies (HMA) and European Medicines Agency (EMA) Big Data Steering Group workplan has been enhanced including work on national regulatory use cases for real-world evidence (RWE), intensified work on artificial intelligence (AI) and public consultation on patient experience data (PED).

The updated Big Data Steering Group (BDSG) workplan continues to evolve to integrate use of big data and data analytics in medicines regulation. he updated workplan contains the following key additions:

[1] Real-world evidence (RWE): DARWIN EU® will address use cases from national regulators and learnings from RWE pilots will be gathered and published.  Work on RWE guidance, at EU and international level, will be informed by public consultations and collaboration with international regulators under the umbrella of ICH will continue.

[2] Real World Data (RWD) quality considerations will be published following a public consultation.

[3] Engagement with patients’ organisations will intensify through a public consultation on Patient Experience Data (PED), dialogue on training needs, workshop on patient registries, a call to populate the metadata and RWD source catalogues with PED, and exploration of use cases to analyse PED to establish their role in regulatory decision-making process.

[4] Analysis of additional data types will be explored with the development of use cases for genomics data, the launch of a ‘proof of concept’ on non-clinical raw data analysis and discussion on Chemistry, Manufacturing and Controls (CMC) data analysis.

[5] Experimentation of advanced analytics, including AI, will continue and the first AI knowledge mining tool for core regulatory processes will be released to the EU regulatory network.

[6] The future European Medicines Regulatory Network data strategy will be developed to prepare for publication in 2025.

A full overview of the timeline can be found here:

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Real World Evidence (RWE) 201 – EU – EMA Big Data Steering Group Updates Its Workplan to Accelerate Transformation to Data-Driven Medicines Regulation2023-12-08T14:14:24+00:00



A tangible example of how real world evidence (RWE) can be used to support label extensions for existing drugs.

Note the FDA’s emphasis on:

“This approval reflects how a well-designed, non-interventional study relying on fit-for-purpose real-world data (RWD), when compared with a suitable control, can be considered adequate and well-controlled under FDA regulations”

Hopefully, we will see similar approvals in Europe and the rest of the World

16 JULY 2021 – Today, the U.S. Food and Drug Administration (FDA)[1] approved a new use for Prograf[2] (tacrolimus) based on a non-interventional (observational) study providing real-world evidence (RWE)[3] of effectiveness. FDA approved Prograf[2] for use in combination with other immunosuppressant drugs to prevent organ rejection in adult and pediatric patients receiving lung transplantation[1].

Prograf[2], originally approved to prevent organ rejection in patients receiving liver transplants, was later approved to prevent organ rejection for kidney and heart transplants as well. The drug has also been routinely used in clinical practice for patients receiving lung transplants. Today’s action marks the first approval of an immunosuppressant drug to prevent rejection in adults and pediatric patients who receive lung transplants. Prograf[2] is the only approved immunosuppressant drug product for this population[1].

This approval reflects how a well-designed, non-interventional study relying on fit-for-purpose real-world data (RWD)[3], when compared with a suitable control, can be considered adequate and well-controlled under FDA regulations. Specifically, the non-interventional study supporting approval for this new indication used RWD from the U.S. Scientific Registry of Transplant Recipients (SRTR)[4], supported by the Department of Health and Human Services. The data were collected on all lung transplants in the U.S. and were supplemented by information from the Social Security Administration’s Death Master File as a trusted repository of mortality data. A dramatic improvement in outcomes was observed among lung transplant patients receiving Prograf[2] as part of their immunosuppression medications compared to the well-documented natural history of a transplanted drug with no or minimal immunosuppressive therapy[1].

In addition to the RWE from the non-interventional study, randomized controlled trials of Prograf[2] used in other solid organ transplant settings provided confirmatory evidence of effectiveness. Additional clinical trial evidence from research publications supports the independent contribution of Prograf[2] as part of a multi-drug immunosuppressive regimen[1].

Prograf[2] should only be prescribed by physicians experienced in immunosuppressive therapy and management of organ transplant and patients receiving the drug should be managed in facilities equipped and staffed with adequate laboratory and supportive medical resources. Prograf[2] is associated with increased risk of developing lymphoma and other malignancies and is associated with increased susceptibility to bacterial, viral, fungal, and protozoal, including opportunistic infections[1].

FDA granted the approval to Astellas Pharma US, Inc[5].


1. FDA Approves New Use of Transplant Drug Based on Real-World Evidence (16 July 2021)

2. PROGRAF (tacrolimus) – Highlights of Prescribing Information

3. FDA – Real-World Evidence

4. U.S. Scientific Registry of Transplant Recipients (SRTR)

5. Astellas – U.S. Food and Drug Administration Expands Indication for PROGRAF® for Prevention of Organ Rejection in Adult and Pediatric Lung Transplant Recipients (20 July 2021)


Real World Evidence (RWE) 101 – The Tuskegee Syphilis Study – Supplement

RWE 101 – The Tuskegee Syphilis Study – Supplement


The Tuskegee Syphilis Study, conducted between 1932 and 1972 by the United States Public Health Service (USPHS), stands as one of the most infamous and ethically questionable experiments in the history of human research. The study intended to observe the natural history of untreated syphilis. Researchers did not collect informed consent from participants. Researchers did not offer treatment, even after it was widely available. The study was terminated after 40 years following publication of news articles about the study.

“The government induced these men to participate in a study in which the government represented that the participants were being treated for whatever their ailments were…They were never told what their ailment was…They never gave their consent to be involved in a study…Nor did they realise they were part of a study until the story broke in July 1972…Treatment was knowingly withheld for 40 years” – Fred D Gray – Attorney, 8th April 1997

Its repercussions have had far-reaching effects on the regulation of observational studies, medical ethics, and trust in healthcare institutions, especially among minority communities.

  1. Introduction of Ethical Guidelines: The Tuskegee study helped accelerate the development of ethical standards for observational studies, notably the Belmont Report in 1979. The report outlined three basic principles: respect for persons, beneficence, and justice. It prescribed informed consent, an understanding of potential risks and benefits, and the equitable selection of research subjects. These principles, born out of a response to the unethical practices in Tuskegee and other studies, have become the bedrock of research ethics.
  2. Introduction of Regulations: In 1974 the National Research Act was signed into law and the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research was formed. In 1991 the Federal Policy for the Protection of Human Subjects (‘Common Rule’) (45 CFR 46) was implemented.
  3. Informed Consent: One of the main lessons from the Tuskegee study was the importance of informed consent. In the study, participants were not told they had syphilis, nor were they informed about the nature of the experiment. As a result of public outcry, it is now mandatory for researchers to provide potential participants with comprehensive information about the study and its potential risks and benefits.
  4. Protection for Vulnerable Populations: The Tuskegee study highlighted the need for special protections for vulnerable populations in observational studies. The mostly poor, uneducated African American men involved were exploited due to their socioeconomic status and lack of access to quality healthcare. The fallout from Tuskegee led to additional safeguards for marginalized populations to prevent similar abuses.
  5. Institutional Review Boards (IRBs): After the Tuskegee study, the requirement for Institutional Review Boards became more widespread. IRBs are responsible for reviewing and monitoring research involving humans to ensure ethical standards are met. Their role is to protect the rights and welfare of the research subjects.
  6. Transparency and Accountability: The Tuskegee Syphilis Study was marked by a lack of transparency and accountability. The study was conducted without adequate oversight or scrutiny. This led to the development of regulations requiring transparency in the conduct of studies, data sharing, and mechanisms for accountability in the case of ethical breaches.
  7. Public Trust and Participation: The Tuskegee study severely damaged public trust, particularly among African Americans, in medical research and healthcare institutions. This has implications for the regulation of observational studies, as it underscores the importance of building and maintaining public trust for successful research participation.
  8. Cultural Competency: The racial implications of the Tuskegee study brought to light the importance of cultural competency in research. Researchers are now required to respect the cultural norms and values of the populations they study, and training in cultural competency has become a norm in many research settings.
  9. Training in Research Ethics: Following the Tuskegee study, training in research ethics became a requirement for investigators conducting human subject research. This training typically includes a discussion of the Tuskegee study as an example of what not to do.
  10. International Impact: The Tuskegee study had a global impact on observational study regulation. The Declaration of Helsinki, a set of ethical principles regarding human experimentation, was updated in response to the ethical violations in Tuskegee and similar studies.

“Medical professionals willingly and intentionally let human beings suffer from a treatable, and then later a curable illness. These researchers knew that mercury and arsenic compounds could treat the disease, but the Tuskegee men did not receive the medicine. Later the researchers knew that penicillin could cure the disease, but again, the Tuskegee men did not get the medicine. They didn’t get treated until the 40 year study was discovered and stopped amid public outcry in 1972. It was a disgraceful episode for American Scientists” – Vice President Al Gore, 16th May 1997 [See also…Presidential Apology]

In conclusion, the Tuskegee Syphilis Study has had a profound impact on the regulation of observational studies in the USA.

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Real World Evidence (RWE) 101 – The Tuskegee Syphilis Study – Supplement2023-08-07T13:51:32+00:00
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