var _paq = window._paq = window._paq || []; /* tracker methods like "setCustomDimension" should be called before "trackPageView" */ _paq.push(['trackPageView']); _paq.push(['enableLinkTracking']); (function() { var u="https://rwrregs.matomo.cloud/"; _paq.push(['setTrackerUrl', u+'matomo.php']); _paq.push(['setSiteId', '1']); var d=document, g=d.createElement('script'), s=d.getElementsByTagName('script')[0]; g.async=true; g.data-privacy-src='//cdn.matomo.cloud/rwrregs.matomo.cloud/matomo.js'; s.parentNode.insertBefore(g,s); })();

About stuart.mccully

This author has not yet filled in any details.
So far stuart.mccully has created 658 blog entries.

Real World Evidence (RWE) 101 – Standard Operating Procedures

RWE 101 – Standard Operating Procedures

Standard Operating Procedures (SOPs) are critical for the operation of any business, particularly in regulated industries like pharmaceuticals where precision, safety, and compliance with regulatory requirements are paramount. For a pharmaceutical company, SOPs for observational studies and clinical trials should be separated due to the distinct nature and objectives of each type of study. Here are the main reasons:
 
[1] Different objectives: Clinical trials are experiments designed to evaluate the safety and efficacy of a new drug or intervention. On the other hand, observational studies are non-interventional; they involve the collection of data without altering the patients’ usual treatment or environment, aiming to observe and analyse patterns, effects, or outcomes.
 
[2] Regulatory requirements: Clinical trials are highly regulated, with strict GxP requirements from bodies like the FDA or EMA. Observational studies, while still regulated, do not fall under the same stringent GxP requirements. Having separate SOPs ensures compliance with the correct set of regulations for each type of study.

[3] Study design and conduct: The design and conduct of clinical trials and observational studies are significantly different. For instance, clinical trials are generally randomized, controlled, and blinded studies. In contrast, observational studies may involve case-control studies, cohort studies, or cross-sectional studies. Different SOPs can specify the appropriate designs, methods and checks for data collection, storage, and analysis in each case.

[4] Patient consent and confidentiality: In clinical trials, patients provide informed consent for the specific interventional treatment they will receive. In observational studies, while consent is still required, it’s often related to access and use of their medical data rather than a specific treatment. Thus, separate SOPs can address these differing requirements.
 
[5] Risk Management: Risks and safety considerations also vary between clinical trials and observational studies. The risks of clinical trials often relate to the new drug or intervention being tested, while observational studies’ risks typically concern data protection and patient privacy.
 
[6] Reporting Results: Different types of studies may also have different reporting requirements, including timelines, formats, and recipients of the information (e.g., regulatory authorities, ethics committees, sponsors).
 
By having separate SOPs, companies ensure that all these aspects are appropriately addressed, leading to better quality, more ethical research, and improved compliance with regulatory requirements. It also helps in training and guiding staff effectively in their roles for different studies.

Share this story...

Real World Evidence (RWE) 101 – Standard Operating Procedures2023-08-07T19:53:39+00:00

Real World Evidence (RWE) 101 – Publications

RWE 101 – Publications

The term RWE stands for Real-World Evidence, which is evidence derived from real-world data (RWD). RWD are data relating to patient health status and/or the delivery of health care routinely collected from a variety of sources.
 
Ethical approval is needed for the publication of RWE studies in international peer-reviewed journals for several key reasons:
 
[1] Participant Protection: Ethical approval ensures that the rights, safety, and well-being of the study participants are protected. It guarantees that the study has been designed to minimize harm and discomfort to the participants.
 
[2] Informed Consent: Ethical review boards (RECs/IRBs) ensure that participants have given informed consent. This means participants are made aware of the nature of the study, its purpose, the procedures involved, the potential risks and benefits, and their rights, including the right to withdraw from the study at any time without penalty.
 
[3] Privacy and Confidentiality: Ethical approval also ensures that the researchers have a plan in place to protect participant’s privacy and confidentiality. This is particularly important in RWE studies, where the data may come from various sensitive sources such as electronic health records, insurance claims databases, patient registries, and more.
 
[4] Avoidance of Bias: Ethics committees help ensure that the study is designed in a way that will minimize bias, increasing the validity of the results.
 
[5] Trustworthiness of the Research: By requiring ethical approval, journals are able to guarantee a certain level of quality control. Ethical approval can indicate that the research has been conducted appropriately and that the results are trustworthy.
 
[6] Compliance with International Standards: Ethical approval ensures that research is conducted in line with the globally recognized ethical guidelines and principles such as the Declaration of Helsinki e.g., the International Committee of Medical Journal Editors “Recommendations” (Link: https://lnkd.in/er-Sj5py). Also, according to the National Health Commission of China, when academic journals publish the results of human life science and medical research, they shall confirm that the research has been approved by the ethics review committee. Researchers should provide relevant proof (Article 29 of the 2023 Ethical Review Measures).
 
By requiring ethical approval, peer-reviewed journals ensure that the research they publish is ethical, credible, and respectful of participant rights. This is crucial in maintaining trust in the research community and the broader public who may ultimately benefit from the research findings.

Share this story...

Real World Evidence (RWE) 101 – Publications2023-08-07T19:41:16+00:00

Real World Evidence (RWE) 101 – Archiving Specifics

RWE 101 – Archiving Specifics

Proper archiving of clinical study documents is an important practice for maintaining the quality, integrity, and usability of study data, and for ensuring regulatory compliance. These aspects are especially important in the context of RWE studies, where the scope and complexity of the regulatory requirements and standards, can differ significantly across and between regions. For example, here are some country-specific archiving timelines for observational drug studies:
 
Argentina = 2 years
Austria = 15 years
Brazil = 5 years
Germany = 10 years
Japan = 5 years
Netherlands = 15 years
South Korea = 3 years
Turkey = 5 years
 
According to ISPE GPP, where there are no specified national or regional requirements for retention of study materials, the archive should be maintained for at least five years after final report or first publication of study results, whichever comes later.
 
Additional considerations when determining what to archive and for how long, include:
 
[1] Legal Protection (Contractual Obligations): Archiving documents can offer protection in the event of legal questions or disputes related to the conduct of the study, data ownership, patient consent, adverse event reporting, etc. If you are a vendor, check study management contracts for any document retention obligations.
 
[2] Real-World Study Document Index (RWS-DI): The RWS-DI is a framework developed by a working group of real-world study (RWS) experts to address the challenges of filing essential documents for non-interventional and observational studies. Designed to be consistent with the TMF RM format and structure, but removes artifacts specific to clinical trials and replaces terminology such as “trial” with “study” and “subject” with “patient.”
 
In conclusion, the process of archiving clinical study documents should not be overlooked, especially in the arena of RWE studies. Regulatory compliance, data validation, legal protection, and future research potential hinge on the effective preservation of these important materials. As the rules can differ wildly from Argentina’s 2-year requirement to Austria and Netherlands’ 15 years, it’s critical to be aware of both regional specifics and overarching guidelines like the ISPE GPP’s five-year rule. Additionally, tools like the RWS-DI provide a specialized framework to ensure that archiving practices are tailored to the unique needs of RWE studies. So, when you’re next managing an observational study, remember – good archiving isn’t just about meeting regulations; it’s about safeguarding the integrity of your study, its results, and the future studies it may inspire.

Share this story...

Real World Evidence (RWE) 101 – Archiving Specifics2023-08-07T19:33:49+00:00

Real World Evidence (RWE) 101 – Archiving Generics

RWE 101 – Archiving Generics

In the context of health research, both observational studies and clinical trials are crucial for understanding disease processes, patient outcomes, and the safety and efficacy of treatments. However, due to varying regulatory requirements and standards, the archiving requirements for these types of studies are distinct. Here are some of the key differences:
 
[1] Regulations and Guidelines: Clinical trials as governed by a global set of ethical and scientific standards, such as ICH GCP. These standards are then adopted into law in different regions, say for instance, through the Regulation EU/536/2014, and 21 CFR 312 in the US. These rules are clear about how to manage, store, and archive data and require specific documents to prove the integrity of the trial data. They also set out how long these crucial documents should be kept (e.g., at least 25 years).
 
On the flip side, observational studies aren’t governed by such unified requirements when it comes to document retention and archiving. They still follow ethical guidelines and good practice principles like the Declaration of Helsinki, ISPE GPP, and STROBE guidelines, but these may not give you exact retention times or archiving mechanisms.
 
[2] Data Collection and Confidentiality: Clinical trials are data-rich; they collect a large amount of confidential and sensitive patient data. Regular sponsor audits and regulatory inspections mean they need to keep robust records. Observational studies, while they also handle sensitive data, usually don’t interact with patients as much and don’t face as many regulatory inspections. So, they’ve traditionally not had to maintain as meticulous records.
 
[3] Data Accessibility: Clinical trial data is often more restricted in terms of who can access it and how it can be shared. This is due to both regulatory needs and commercial interests. Observational data, though, is often used for big-picture disease studies, and it’s usually designed to be more shareable – as long as it’s anonymized and ethical procedures are followed.
 
It’s important to remember that what I’ve explained are general patterns. The exact requirements can change based on region, the type of data you’re dealing with, and even who’s funding your work. If you need specific guidance, don’t hesitate to reach out to an expert or regulatory authority in your area.

Share this story...

Real World Evidence (RWE) 101 – Archiving Generics2023-08-07T18:44:26+00:00

Real World Evidence (RWE) 101 – Study Close-out

RWE 101 – Study Close-Out

Closing out an observational study involves several key steps to ensure that all study activities are concluded properly, and data integrity is maintained. Here are the typical activities involved:
 
[1] Data Lock and Validation: The first step in the study closeout process is to ensure all data is collected, cleaned, and ready for analysis. This involves resolving any outstanding queries, performing a final quality control check on the data, and then locking it for final analysis. This step also requires validation of data by checking the accuracy and consistency of the data collected.
 
[2] Disposition of Study Materials: Any remaining study materials, such as unused data collection forms or materials used for measurements, need to be disposed of appropriately. Any biological samples collected during the study also need to be handled as per the protocol and regulatory guidelines, which could mean returning, destroying, or continuing to store them, as agreed.
 
[3] Final Report Preparation: After data is locked and validated, the study team will analyse the data and prepare a final study report. This report content and format should follow regulatory requirements where applicable e.g., EU PASS Report.
 
[4] Archiving Study Documents: All study documents, including the study protocol, data collection forms, consent forms, and correspondence, should be properly archived according to the regulatory requirements and the company’s SOPs.
 
[5] Site Closeout Visits: If the study was performed across multiple sites, each site may need a closeout visit. These visits serve to confirm that all necessary activities have been completed, including data collection, storage or destruction of study materials, and archiving of site documents.
 
[6] Contract Closure: Finally, any contracts related to the study, such as those with study sites or service providers, need to be formally closed. This could involve confirming that all deliverables have been met, all payments have been made, and all obligations are fulfilled.
 
[7] Notification of End of Study: It’s important to inform the relevant ethical review board (IRB/REC) or regulatory authority that the study has ended, and provide them with a summary of the study’s findings, if required.
 
[8] Communicating Results: Depending on the nature of the study and its sponsorship, the results may need to be communicated to a variety of stakeholders. This could include the sponsor, study participants, health authorities, and potentially the wider scientific community through publications.
 
These activities help ensure that the study is closed out in a systematic and organized manner, which is critical for compliance, data integrity, and future use or inspection of the study data and materials. The exact nature and sequence of the activities may vary depending on the specifics of the study, the regulatory framework, and the procedures established by the sponsor.

Share this story...

Real World Evidence (RWE) 101 – Study Close-out2023-08-07T18:36:39+00:00

Real World Evidence (RWE) – TMF Reference Model versus the Real-World Study Document Index (RWS-DI)

RWE 101 – TMF Reference Model versus the Real-World Study Document Index (RWS-DI)

The Real World Study-Document Index (RWS-DI) is a framework developed by a working group of RWE experts to address the challenges of filing essential documents for non-interventional and observational studies. The RWS-DI is designed to be consistent with the TMF Reference Model (TMF RM) format and structure, but removes artifacts specific to clinical trials and replaces terminology to reflect the unique nature of real-world studies.
 
Key differences between the TMF Reference Model (TMF RM) and the Real World Study-Document Index (RWS-DI) are:
 
[1] TMF Reference Model:
– An industry-adopted reference structure for the TMF that takes the form of an index.
– Provides a model of a complete TMF, which can then be customized as needed for a specific clinical study.
– Assigns documents to a comprehensive taxonomy complete with standard nomenclature to enable consistent filing.
– Developed primarily from a sponsor perspective, which makes it difficult for sites to adopt due to its larger scope and non-intuitive terminology.

Link: https://lnkd.in/eV4cH4At
 
[2] Real World Study-Document Index:
– A framework developed by a working group of real-world study (RWS) experts to address the challenges of filing essential documents for non-interventional and observational studies.
– Based on a prospective study design to provide maximum coverage of the potential document or artifact types across the range of real-world study designs.
– Designed to be consistent with the TMF RM format and structure, but removes artifacts specific to clinical trials and replaces terminology such as “trial” with “study” and “subject” with “patient.”
– A stand-alone deliverable that is expected to evolve to reflect user community requirements.

Link1: https://lnkd.in/eNUnsKR6
Link2: https://lnkd.in/eU6vf8qN
 
Overall, it is important for organizations to understand the regulatory requirements for TMF management and determine which framework is best suited for their specific study design.

Share this story...

Real World Evidence (RWE) – TMF Reference Model versus the Real-World Study Document Index (RWS-DI)2023-08-07T18:29:01+00:00

Real World Evidence (RWE) 101 – ISF vs TMF

RWE 101 – ISF vs TMF

Investigator Site File (ISF) and Trial (Study) Master File (TMF) are key elements in managing clinical and observational studies. They are distinct but interconnected, and play vital roles in ensuring the documentation, compliance, and overall management of a research study is handled properly.

[1] Investigator Site File (ISF): This is a collection of documents, images, and digital media that an investigator (or a site conducting the research) uses to record the administrative and procedural documentation related to the study. It includes items such as the protocol, study approvals, consent forms, participant information, communication records, and site-specific documentation. The ISF helps demonstrate the site’s compliance with the principles of Good Clinical Practice (GCP) and the applicable regulatory requirements.

[1] Trial Master File (TMF): This is a collection of essential documents that allow the conduct of a clinical trial to be reconstructed and evaluated. It is intended to serve both the interests of the sponsor and the regulatory bodies. The TMF includes a broad range of information, such as the protocol, ethics committee approval, data safety monitoring board reports, informed consent forms, and any other relevant documentation. It should include all the key documents from the ISF, but also additional information at a study-wide level.

Key differences between the ISF and TMF include:

[1] Scope: ISF focuses on documentation at the site level, specific to each location where the study is conducted. TMF encompasses the entire study and includes all sites involved in the study, maintaining a complete record of all essential documents.

[2] Control: ISF is usually maintained by the investigator or staff at the site where the study is being conducted. The TMF, on the other hand, is typically managed and controlled by the study sponsor.

[3] Documentation: While both files hold critical study documents, the ISF is more focused on site-specific operational documents (e.g., informed consent forms), while the TMF has more strategic and overall study control documents.

[4] Purpose: While both files are crucial for audits and inspections, the ISF is particularly important for demonstrating the compliance of the individual site, while the TMF helps provide a comprehensive overview of the study’s conduct and ensures that the trial can be adequately reconstructed if necessary.

Please note that while these are general guidelines, the exact nature of the ISF and TMF may vary depending on the specifics of the study, the regulatory framework, and the procedures established by the sponsor.

Share this story...

Real World Evidence (RWE) 101 – ISF vs TMF2023-08-07T18:20:46+00:00

Real World Evidence (RWE) 101 – Study Conduct

RWE 101 – Study Conduct

Once the study has been set up, the study conduct phase begins. This phase includes several key activities that ensure the smooth running of the study and the collection of high-quality data. Here are some of the key study conduct activities in the context of Real-World Evidence (RWE) studies:
 
[1] Patient Enrolment and Follow-up: After obtaining informed consent, patients are enrolled in the study according to the criteria outlined in the study protocol. The enrolled patients and/or their healthcare data are then followed up at regular intervals. Observational study designs seek to mirror routine clinical practice as closely as possible.
 
[2] Data Collection: This involves gathering data according to the study protocol. The data can come from a variety of sources, such as electronic health records (EHRs), insurance claims databases, patient registries, or directly from patients via surveys or interviews. Data collection must be systematic and standardized to ensure data quality and reliability.
 
[3] Monitoring and Quality Control: Monitoring is done (recommended by the FDA and AEMPs) to ensure that the study is being conducted according to the protocol and that data is being collected accurately and consistently (especially safety data). This could involve site visits by clinical research associates, remote monitoring, or data audits.
 
[4] Safety Monitoring: Any adverse events or side effects reported by patients to/by clinicians are recorded and reported to the appropriate authorities. Reporting requirements differ by region.
 
[5] Interim Analysis: Depending on the study design, interim analyses may be conducted at certain points during the study. This can allow early detection of safety issues or indications of effectiveness.
 
[6] Vendor Management: If vendors are being used for services such as data analysis or lab testing, regular communication is required to ensure that the work is being done according to the agreed timelines and standards.
 
[7] Regulatory Compliance: Throughout the study, all(regional) regulatory requirements must be followed. This includes maintaining proper documentation, protecting patient privacy, and reporting to regulatory bodies as required.
 
[8] Communication and Reporting: Regular updates about the study progress are typically provided by the study sponsor, to the investigators, the ethics committee or IRB, and any other relevant stakeholders.
 
These activities continue until all patients have been enrolled and all data has been collected. The study conduct phase is critical for ensuring that the data collected is reliable and that the results of the study will be scientifically valid and useful for informing healthcare decisions.

Share this story...

Real World Evidence (RWE) 101 – Study Conduct2023-08-07T18:13:03+00:00

Real World Evidence (RWE) 101 – Monitoring

RWE 101 – Monitoring

Monitoring requirements for Real-World Evidence (RWE) studies may differ from those of traditional randomized controlled trials due to the nature of data collection and the sources of data involved.
 
According to recent (2021) draft FDA Guidance: Study monitoring may be focused on maintaining the reliability of the RWD and data integrity, beginning with extraction of the data from its origin through data curation and transformation and reporting of results.
 
Here are the key monitoring considerations for RWE studies:
 
[1] Data Quality and Integrity: This is the core of any monitoring activity. In RWE studies, data is often sourced from electronic health records, claims databases, registries, or directly from patients. The accuracy and consistency of this data should be monitored to ensure its validity. This can involve cross-checking data from different sources, checking for missing or inconsistent data, and using statistical methods to identify potential data errors.
 
[2] Regulatory Compliance: Even though RWE studies often use pre-existing data, they still need to comply with relevant regulations. For example, patient data must be handled in accordance with data protection laws such as the General Data Protection Regulation (GDPR) in the EU or the Health Insurance Portability and Accountability Act (HIPAA) in the US.
 
[3] Protocol Adherence: While protocol deviations may be less of a concern with RWE studies than with traditional trials (since there is no intervention being delivered), it’s still essential to monitor whether the study is being conducted as planned. For example, are the correct data elements being collected, and is the data being analysed according to the pre-specified plan?
 
[4] Safety Monitoring: Even though RWE studies are typically observational and don’t involve interventions, they still need to monitor for any potential safety signals that emerge. For instance, if the study involves a drug or device, any adverse events or side effects reported in the data nust be investigated.
 
[5] Ethical Compliance: Even though the patients involved in RWE studies may not be directly participating in the way they would in a clinical trial, ethical considerations still apply. If the study involves direct contact with patients (e.g., via surveys), the consent process and protection of patient rights should be monitored.
 
[6] Analysis and Reporting: As data is collected and analysed, it should be checked for completeness and accuracy. Any interim analyses or final reports should be reviewed to ensure they accurately represent the data collected and follow the pre-specified analysis plan.
 
In summary, while the specifics of monitoring may vary somewhat, the goal remains the same: to ensure the study is conducted with high standards of quality, integrity, and ethics, and that the data collected is reliable and valid.

Share this story...

Real World Evidence (RWE) 101 – Monitoring2023-08-07T17:56:59+00:00

Real World Evidence (RWE) 101 – eConsent

RWE 101 – eConsent

Electronic consent or eConsent refers to the process of using electronic systems and processes to convey information related to the study and to obtain and document participant consent. While eConsent brings numerous benefits to the table, such as improved participant comprehension, streamlined workflows, and easier tracking and managing of consent versions, it is not universally accepted in Real-World Evidence (RWE) studies due to several reasons:

[1] Regulatory Variations: Regulatory guidelines and requirements vary across different jurisdictions and countries. Some regions may not yet have clear guidance or regulations that specifically endorse eConsent, causing uncertainty about its legal validity.

[2] Digital Divide: While digital technologies are pervasive (increasingly accepted), access to and familiarity with these technologies is not universal. Some potential study participants may lack the technology needed for eConsent or may not be comfortable using it, which could potentially exclude certain populations from participation (introducing bias).

[3] Data Security and Privacy Concerns: As with any digital system, there are concerns related to data security and privacy. Participants may worry about their personal information being mishandled or leaked, especially given the sensitivity of health data.

[4] Implementation Costs: Setting up a secure, user-friendly eConsent system that can also meet all regulatory requirements is a significant investment. Small research entities or those in low-resource settings might find it challenging to bear these costs.

[5] Technical Hurdles: eConsent systems require a level of technical infrastructure and support to function effectively. This can include the need for reliable internet connectivity, ongoing technical support, regular software updates, and more.

Despite these challenges, the adoption of eConsent is increasing due to the evolution of technology, better regulatory support, and the COVID-19 pandemic necessitating remote study processes. As these challenges are addressed over time, it’s expected that eConsent will become a more universally accepted practice in RWE studies.

 

Share this story...

Real World Evidence (RWE) 101 – eConsent2023-08-07T17:48:32+00:00
Help

About Us

Contact Us

Our Values

SSO Login

Follow Us

Newsletter

LinkedIn

[…]

Legal Info

Privacy Policy

Terms and Conditions

Copyright 2026 | Real-World Research Limited | All Rights Reserved |

This website uses cookies and third party services. Settings
OK Reject

Cookies

We use analytical tools (Google Analytics) to help us improve the user experience. We DO NOT sell or use any of this data for any purpose beyond improving the design and usability of our own website (rwr-regs.com).
Go to Top