stuart.mccully, Author at rwr-regs

Real World Evidence (RWE) 101 – Observational Study vs Non-Interventional Study
Real World Evidence (RWE) 101 – Observational Study vs Non-Interventional Study

2023, RWE 101

Real World Evidence (RWE) 101 – Observational Study vs Non-Interventional Study

RWE 101 – Observational Study vs Non-Interventional Study

In the context of real-world evidence (RWE), the terms “observational study” and “non-interventional study” are often used interchangeably to refer to studies that collect data outside the controlled environment of a clinical trial. However, it’s worth noting that some subtle differences can exist based on the specific context or regulatory guidelines. Here’s an overview:

[1] Observational Study: An observational study is a research design where researchers observe and collect data on participants without intervening or administering any specific treatment. Observational studies aim to analyze associations, correlations, or patterns in real-world settings. They can be prospective (following participants over time) or retrospective (analyzing existing data or medical records).

[2] Non-interventional Study: A non-interventional study is a study type (EU and US regulatory definition) that does not involve any healthcare or treatment interventions imposed by researchers. It is often used as an umbrella term for studies that collect data in real-world settings, without manipulating variables. Non-interventional studies are primarily focused on describing, analyzing, or assessing outcomes, exposure, or associations.

It’s important to note that regulatory guidelines and definitions may vary across different regions and agencies. For instance, the US FDA’s guidance on RWE refers to “real-world studies”, “observational Studies”, and “non-interventional (observational) studies”, while the European Union Clinical Trials Regulation (Regulation EU/536/2014) uses the term “non-interventional studies.” However, in practice, the intent of these studies—collecting data without actively intervening—is often similar.

In the context of RWE, both observational studies and non-interventional studies typically leverage real-world data sources such as electronic health records, claims databases, registries, surveys, or patient-reported outcomes. They aim to generate evidence (real world evidence) on treatment outcomes, comparative effectiveness, safety profiles, and other healthcare-related factors.

Ultimately, the precise terminology used may vary, but the fundamental principle is that observational studies and non-interventional studies within the context of RWE both involve the collection and analysis of real-world data without actively imposing healthcare or treatment interventions on participants.

Real World Evidence (RWE) 101 – Observational Study vs Non-Interventional Studystuart.mccully2023-08-07T13:29:05+00:00

Real World Evidence (RWE) 101 – Are Non-Interventional Studies Regulated?
Real World Evidence (RWE) 101 – Are Non-Interventional Studies Regulated?

2023, RWE 101

Real World Evidence (RWE) 101 – Are Non-Interventional Studies Regulated?

RWE 101 – Are Non-Interventional Studies Regulated?

Yes, non-interventional studies (NIS) are regulated. While the specific regulations and requirements may vary by country, there are generally guidelines and provisions in place to ensure the conduct and reporting of non-interventional studies meet certain standards.

Here are some key points related to the regulation of non-interventional studies:

Ethical Considerations: Non-interventional studies involving human participants must adhere to ethical principles and guidelines (i.e., Declaration of Helsinki) and be approved by an ethics committe (IRB/REC). These guidelines often cover aspects such as informed consent, confidentiality, privacy protection, and the rights and welfare of study participants.

Data Protection: Regulations related to data protection and privacy, such as the EU General Data Protection Regulation (GDPR), are applicable to non-interventional studies. Researchers must ensure that the collection, storage, and processing of personal data comply with these regulations.

Regulatory Oversight: Regulatory authorities may have oversight over non-interventional studies, particularly when the studies are the results of a regulatory commitment (e.g., PMRs and PASS). In the EU, for example, the EMA provides guidance on non-interventional post-authorisation safety studies (PASS) (GVP Module VIII).

Good Pharmacovigilance Practices (EU): Non-interventional studies focused on post-authorization safety assessments of medicinal products are subject to good pharmacovigilance practices. These practices include the collection, analysis, and reporting of adverse drug reactions and safety data.

Reporting Requirements: Non-interventional studies may have reporting requirements (e.g., EU PAS Register) to ensure transparency and accountability. This may include the submission of study protocols, study results, safety updates, or other relevant data to regulatory authorities or ethics committees.

It’s important to note that the specific regulations and requirements for non-interventional studies can vary between countries and regions. Researchers conducting non-interventional studies should be familiar with the applicable regulations in their jurisdiction and seek guidance from regulatory authorities, ethics committees, or relevant professional organizations to ensure compliance with the required standards.

Real World Evidence (RWE) 101 – Are Non-Interventional Studies Regulated?stuart.mccully2023-08-07T13:12:49+00:00

Real World Evidence (RWE) 101 – Postmarket Requirements (PMR) vs Post-Authorisation Safety Studies (PASS)
Real World Evidence (RWE) 101 – Postmarket Requirements (PMR) vs Post-Authorisation Safety Studies (PASS)

2023, RWE 101

Real World Evidence (RWE) 101 – Postmarket Requirements (PMR) vs Post-Authorisation Safety Studies (PASS)

RWE 101 – Postmarket Requirements (PMR) vs Post-Authorisation Safety Studies (PASS)

In the context of real-world evidence (RWE) and regulatory frameworks, postmarket requirements (PMRs) and post-authorization safety studies (PASS) are two distinct concepts that focus on monitoring and assessing the safety and effectiveness of medical products after they have been approved or authorized for use. Here’s an explanation of each:

Postmarket Requirements (USA): Postmarket requirements refer to the obligations imposed by the US FDA on manufacturers or sponsors of medical products (such as drugs and biologics) after they have been approved for marketing. These requirements are intended to gather additional data and monitor the product’s safety and effectiveness in real-world settings and INCLUDE observational studies that sponsors are required to conduct.

Compliance with these requirements ensures ongoing evaluation and surveillance of the product’s safety and effectiveness throughout its lifecycle.

Post-Authorization Safety Studies (EU): Post-authorization safety studies (PASS) are specific studies conducted to further assess the safety profile of a medical product in real-world settings after it has been authorized for use. PASS is a type of post-marketing study designed to gather additional safety data that may not have been captured during pre-market clinical trials due to the limited sample size, restricted patient population, or duration of the trials.

Key aspects of post-authorization safety studies include:

Study design: PASS typically involves observational study designs, such as cohort studies or case-control studies, to evaluate the safety outcomes associated with the product’s use in a larger patient population.

Sample size: PASS often involves a larger number of participants than pre-market clinical trials to increase the likelihood of detecting rare or long-term safety events.

Data collection: Data for non-interventional PASS is collected from real-world sources, such as electronic health records, claims databases, registries, or other healthcare databases.

Safety outcomes: The primary focus of PASS is to assess and monitor the occurrence of safety events, adverse drug reactions, or any potential safety concerns associated with the product’s use.

Post-authorization safety studies are typically conducted as a regulatory requirement, based on the authorization conditions set by the EMA (i.e., Category 1 and 2 PASS). The findings from these studies contribute to ongoing risk-benefit assessments of the product and inform regulatory decision-making, labelling updates, or risk management strategies.

Overall, postmarket requirements encompass a broader set of obligations imposed on manufacturers after a product’s approval, while post-authorization safety studies specifically focus on conducting additional studies to assess the safety profile of authorized medical products in real-world settings.

Real World Evidence (RWE) 101 – Postmarket Requirements (PMR) vs Post-Authorisation Safety Studies (PASS)stuart.mccully2023-08-07T13:02:45+00:00

Real World Evidence (RWE) 101 – ‘Interventional’ Clinical Trial vs Non-Interventional Study
Real World Evidence (RWE) 101 – ‘Interventional’ Clinical Trial vs Non-Interventional Study

2023, RWE 101

Real World Evidence (RWE) 101 – ‘Interventional’ Clinical Trial vs Non-Interventional Study

RWE 101 – ‘Interventional’ Clinical Trial vs Non-Interventional Study

Interventional Clinical Trial: In this type of study, researchers actively intervene by assigning participants to different groups, administering specific treatments, or manipulating variables. The primary objective is to assess the safety and efficacy of new interventions e.g., drug or medical device.

Key characteristics of interventional clinical trials include:

Randomization: Participants are randomly assigned to different groups, such as the experimental group receiving the intervention and the control group receiving a placebo or standard treatment.

Intervention: Researchers actively administer a specific treatment or intervention to the participants.

Control Group: There is often a control group that receives a placebo or standard treatment for comparison.

Primary Outcomes: Trials are designed to measure predefined primary outcomes, such as improvements in health outcomes, survival rates, or reduction in symptoms.

Regulatory Oversight: Interventional trials require regulatory approval and are usually subject to stricter (risk-proportionate) regulations than non-interventional studies.

Non-interventional Study: These studies focus on collecting data without any active healthcare or treatment intervention imposed by the researchers. Researchers observe and collect information from participants in their natural settings (real world settings) or through retrospective analysis of existing data (secondary use of existing data).

Key characteristics of non-interventional studies include:

Observation: Researchers observe participants and collect data without actively intervening in the healthcare management of the participant or administering any specific treatment (treatment intervention).

Natural Setting: Data is collected in the real-world clinical practice or from existing databases, medical records, surveys, or interviews.

Descriptive Analysis: Non-interventional studies often aim to describe and analyze associations, relationships, patterns, or risk factors in the population under study.

Retrospective or Prospective: Data can be collected retrospectively by analyzing past records or prospectively by following participants over time.

No Randomization: Participants are not randomly assigned to groups, and treatment decisions are made by healthcare providers according to routine clinical practice.

Regulatory Oversight: Every country regulates non-interventional studies differently. The regulatory burden can therefore be much higher than expected.

Both ‘interventional’ clinical trials and non-interventional studies play important roles in advancing medical knowledge. Interventional trials provide more rigorous evidence for evaluating new interventions, while non-interventional studies offer insights into real-world effectiveness, population health, and long-term outcomes.

Real World Evidence (RWE) 101 – ‘Interventional’ Clinical Trial vs Non-Interventional Studystuart.mccully2023-08-07T12:55:06+00:00

Real World Evidence (RWE) 101 – Are the terms ‘clinical study’ and ‘clinical trial’ synonymous in the context of non-interventional studies?
Real World Evidence (RWE) 101 – Are the terms ‘clinical study’ and ‘clinical trial’ synonymous in the context of non-interventional studies?

2023, RWE 101

Real World Evidence (RWE) 101 – Are the terms ‘clinical study’ and ‘clinical trial’ synonymous in the context of non-interventional studies?

RWE 101 – Are the terms ‘clinical study’ and ‘clinical trial’ synonymous in the context of non-interventional studies?

No, “clinical study” and “clinical trial” are not necessarily synonymous in the context of non-interventional studies in the EU.

In general, a clinical study refers to any investigation involving human participants that is intended to discover or verify the clinical, pharmacological or other pharmacodynamic effects of one or more medicinal products, or to identify any adverse reactions to one or more medicinal products. This can include both (interventional) clinical trials and non-interventional studies.

A clinical trial, on the other hand, specifically refers to a type of interventional clinical study where one or more medicinal products are tested in human participants with the aim of evaluating their safety and/or efficacy i.e., there is a treatment intervention involving a medicinal product.

Non-interventional studies (NIS) are observational studies that do not involve any treatment interventions or protocol-dictated administration of a medicinal product. They are designed to observe patients in their natural clinical setting and collect data on the outcomes of a specific drug or treatment intervention.

So, while a clinical trial is a type of clinical study, not all clinical studies are clinical trials.

Revision 2 of ICH GCP caused confusion to those of us who work with non-interventional studies. The glossary claimed that a ‘clinical trial’ was synonymous with a ‘clinical study’ (Section 1.12 of ICH GCP(R2)). This works if you conduct clinical trials (they are a type of clinical study), but not if you conduct non-interventional studies, which are a type of ‘clinical study other than a clinical trial’ (Article 2.2(4) of Regulation EU/536/2014).

The (draft) Revision 3 of ICH GCP includes a new definition of ‘clinical trial’ provided in the Glossary, which removes any confusion regarding clinical trial vs clinical study.

Clinical Trial = Any interventional investigation in human participants intended to discover or verify the clinical, pharmacological and/or other pharmacodynamic effects of an investigational product(s); and/or to identify any adverse reactions to an investigational product(s); and/or to study absorption, distribution, metabolism and excretion of an investigational product(s) with the object of ascertaining its safety and/or efficacy.

Real World Evidence (RWE) 101 – Are the terms ‘clinical study’ and ‘clinical trial’ synonymous in the context of non-interventional studies?stuart.mccully2023-08-07T12:48:43+00:00

Real World Evidence (RWE) 101 – The Importance of Regulatory Definitions
Real World Evidence (RWE) 101 – The Importance of Regulatory Definitions

2023, RWE 101

Real World Evidence (RWE) 101 – The Importance of Regulatory Definitions

RWE 101 – The Importance of Regulatory Definitions

“Words are powerful”

Regulatory definitions are important in the context of real-world evidence (RWE) studies and real-world research for several reasons:

[1] Consistency: Regulatory definitions provide a consistent framework for generating and evaluating RWE across different stakeholders, including regulatory agencies, industry, and academia. By providing a clear and consistent definition of RWE, stakeholders can ensure that they are using the same language and criteria for evaluating the quality and relevance of RWE.

[2] Standards: Regulatory definitions help establish standards for the use of RWE in regulatory decision-making. For example, regulatory definitions may specify the types of RWE that are acceptable for use in regulatory submissions, the study designs that are appropriate for generating RWE, and the quality standards that must be met to ensure the reliability and validity of RWE.

[3] Decision-making: Regulatory definitions facilitate regulatory decision-making by providing a clear framework for evaluating the quality and relevance of RWE. By establishing clear criteria for evaluating RWE, regulatory agencies can make more informed decisions about the safety, efficacy, and quality of healthcare products.

[4] Transparency: Regulatory definitions promote transparency by providing a clear and consistent framework for generating and evaluating RWE. This can help ensure that stakeholders are aware of the criteria used to evaluate RWE and can provide input into the development of regulatory definitions.

[5] Compliance: Regulatory definitions help ensure compliance with regulatory requirements. By providing a clear definition of RWE and the standards for generating and evaluating it, stakeholders can ensure that their studies and research meet regulatory requirements.

In summary, regulatory definitions are important in the context of RWE studies and real-world research because they provide consistency, establish standards, facilitate decision-making, promote transparency, and ensure compliance with regulatory requirements. By providing a clear and consistent framework for generating and evaluating RWE, regulatory definitions can help stakeholders make more informed decisions about the safety, efficacy, and quality of healthcare products.

Real World Evidence (RWE) 101 – The Importance of Regulatory Definitionsstuart.mccully2023-08-07T12:42:16+00:00

Real World Evidence (RWE) 101 – Regulatory Compliance
Real World Evidence (RWE) 101 – Regulatory Compliance

2023, RWE 101

Real World Evidence (RWE) 101 – Regulatory Compliance

RWE 101 – Regulatory Compliance

Regulatory compliance in the context of real-world evidence (RWE) refers to ensuring that the generation and use of RWE for regulatory purposes are in accordance with applicable laws, regulations, and guidelines. RWE is increasingly being used to support regulatory decision-making in healthcare, particularly in the evaluation of the safety and effectiveness of medical products.

To ensure regulatory compliance when using RWE, organizations must follow the regulatory requirements and guidelines set forth by regulatory agencies such as the FDA in the United States, the EMA in the European Union, and other national regulatory bodies. These requirements and guidelines include criteria for the selection and use of RWE sources, study design, data quality, data privacy, and transparency.

For example, the FDA has published guidance on the use of RWE in regulatory decision-making, which outlines the criteria for using RWE to support the approval of new indications for existing drugs and to satisfy post-marketing study requirements. The guidance stresses the importance of ensuring that RWE studies are designed to address the regulatory question at hand, have appropriate data quality, and include appropriate statistical analyses.

In addition, regulatory compliance in the context of RWE also requires organizations to adhere to ethical standards for the protection of human subjects and patient privacy. Organizations must ensure that RWE studies are conducted in accordance with ethical principles, and that the data collected and analyzed are anonymized, pseudoanonymised, or de-identified to protect patient privacy.

Overall, regulatory compliance in the context of RWE requires organizations to carefully follow regulatory requirements and guidelines to ensure that the RWE generated and used for regulatory purposes is of high quality, meets ethical standards, and meets the regulatory agency’s criteria for acceptability.

Real World Evidence (RWE) 101 – Regulatory Compliancestuart.mccully2023-08-07T12:34:31+00:00

Real World Evidence (RWE) 101 – Regulatory Intelligence
Real World Evidence (RWE) 101 – Regulatory Intelligence

2023, RWE 101

Real World Evidence (RWE) 101 – Regulatory Intelligence

RWE 101 – Regulatory Intelligence

In the context of real-world evidence (RWE) and real-world research (RWR), regulatory intelligence refers to the process of gathering, analyzing, and interpreting regulatory information from various sources to support compliance with regulatory requirements and inform decision-making.

Regulatory intelligence can help stakeholders in the healthcare industry, such as pharmaceutical companies, medical device manufacturers, and healthcare providers, to understand and navigate the complex and ever-changing regulatory landscape. It involves tracking and analyzing regulatory developments, including new and updated regulations, guidance documents, and policies, as well as monitoring regulatory enforcement actions, such as warning letters and product recalls.

By staying up-to-date with regulatory requirements and trends, stakeholders can better assess the potential regulatory implications of RWE and RWR studies, ensure compliance with relevant regulations, and make informed decisions about product development, clinical trials, and post-market surveillance.

In short…regulatory intelligence is a critical component of RWE and RWR that helps ensure that stakeholders are aware of and able to comply with regulatory requirements in their respective fields.

Real World Evidence (RWE) 101 – Regulatory Intelligencestuart.mccully2023-08-07T12:28:28+00:00

Real World Evidence (RWE) 101 – Regulatory Science
Real World Evidence (RWE) 101 – Regulatory Science

2023, RWE 101

Real World Evidence (RWE) 101 – Regulatory Science

RWE 101 – Regulatory Science

Regulatory science is a field of study that involves the application of scientific methods, principles, and data to the development and evaluation of regulatory policies, standards, and practices. In the context of real-world evidence (RWE), regulatory science plays an important role in evaluating the safety, efficacy (effectiveness), and quality of healthcare products and in developing evidence-based regulatory decisions.

Regulatory science in the context of RWE focuses on the use of RWE to support regulatory decision-making. This involves evaluating the quality and relevance of RWE for specific regulatory purposes, such as assessing the effectiveness of a new drug or medical device in a real-world setting. Regulatory science also involves developing and refining methodologies for generating and analyzing RWE, such as observational studies or real-world randomized controlled trials (e.g., pragmatic clinical trials, cluster randomized trials etc).

The use of RWE in regulatory decision-making is becoming increasingly important as stakeholders seek to better understand the real-world performance of healthcare products and as regulators seek to make more informed decisions based on the best available evidence. Regulatory science provides a framework for evaluating the quality and relevance of RWE and for ensuring that it is used appropriately in regulatory decision-making.

In summary, regulatory science in the context of RWE is a field of study that focuses on the use of scientific methods and data to support regulatory decision-making. It involves evaluating the quality and relevance of RWE, developing and refining methodologies for generating and analyzing RWE, and ensuring that RWE is used appropriately in regulatory decision-making.

Real World Evidence (RWE) 101 – Regulatory Sciencestuart.mccully2023-08-07T12:19:12+00:00

Real World Evidence (RWE) 101 – NICE Real World Evidence Framework
Real World Evidence (RWE) 101 – NICE Real World Evidence Framework

2023, RWE 101

Real World Evidence (RWE) 101 – NICE Real World Evidence Framework

RWE 101 – NICE Real World Evidence Framework

The UK’s National Institute for Health and Care Excellence (NICE) has developed a Real World Evidence (RWE) Framework to help evaluate the effectiveness and value of healthcare interventions using real-world data.

The key points of the NICE RWE framework include:

[1] Definition of RWE: Real-world data (RWD) are data collected outside of clinical trials, from sources such as electronic health records, claims databases, and patient registries. RWE is the use of RWD to generate evidence on the effectiveness, safety, and value of healthcare interventions.

[2] Scope of RWE: The NICE RWE Framework focuses on using RWE to inform decisions about the effectiveness and value of healthcare interventions in the UK.

[3] Quality and reliability of RWE: NICE emphasizes the need for high-quality and reliable RWE, which should meet certain standards in terms of data completeness, accuracy, consistency, and validity.

[4] Applicability of RWE: NICE recommends that RWE should be used in combination with other types of evidence, such as randomized controlled trials, to ensure that it is applicable to the population of interest and that the findings are robust.

[5] Analysis and interpretation of RWE: The NICE RWE Framework provides guidance on how to analyze and interpret RWE, including methods for adjusting for confounding factors and biases.

[6] Transparency and reproducibility: NICE emphasizes the importance of transparency and reproducibility in RWE studies, which should be clearly documented and reported to enable independent validation and replication.

[6] Ethical considerations: NICE highlights the need for ethical considerations in RWE studies, including data privacy and security, informed consent, and protection of vulnerable populations.

Overall, the NICE RWE Framework provides a structured approach to using real-world data to inform healthcare decision-making, while ensuring that the data is of high quality and the studies are conducted ethically and transparently.

Real World Evidence (RWE) 101 – NICE Real World Evidence Frameworkstuart.mccully2023-08-07T12:13:03+00:00

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