Electronic Trial Master File (eTMF) solutions are quickly becoming an essential option for managing clinical trial documentation. This helps in replacing paper trial master files and clunky file shares. Earlier, organizations used to face a lot of challenges that come from managing trial master file content on paper or in file share systems. The effort required to locate, manage and collaborate on important documents in a timely manner has caused many organizations to search for more efficient solutions

eTMF systems are gaining widespread acceptance, however, many organizations that seek this solution are still not completely familiar with the core features of an eTMF. In the following article, you will get to know some of the most powerful features found in an eTMF software that clinical organizations should be looking for.

Below are the features you should essentially look for while searching the perfect eTMF system for your organization:

1. Prebuilt DIA TMF Reference Model & Configurable Organization / Sponsor Specific TMF Reference models:

The TMF Reference Model provides standardized taxonomy and metadata and outlines a reference definition of TMF content using standard nomenclature. DIA is the reference model for TMF which is widely used and accepted by most of the global companies and regulators. The eTMF system should come with a prebuilt DIA reference model hierarchy and the system should automatically create the structures for Study, Country, and Site level documents.

Although the DIA reference model is important, it is equally important that the system should allow organizations to define their own TMF structures and sponsor specific organization folders. The system should support customizing the existing DIA TMF model or configuring Organization / Sponsor specific TMF structures.

2. File Planning & Milestones Setup for Study, Countries and Sites:

The system should allow companies to setup milestones at the study level, country level, and site level and plan on what documents and how many numbers of mandatory and optional documents that are targeted to be collected.

Once a file plan and milestones plan are setup for a study, the system should be capable of tracking the clinical trial document in accordance to the plan and alert users if some of the sites are not meeting the plan and milestone due dates

This is one of the mandatory features for an eTMF system. Without this feature the system becomes a simple File sharing platform.

3. Live Tracking of Missing Documents & Document Statues:

Based on the file plan setup for a Study, Country and Site, the system should highlight the status of the document along with missing documents to monitor the TMF compliance at every level.

4. Bulk Upload / Quick Upload & Flexible File Indexing:

The system should allow users to upload documents in bulk where in hundreds of documents can be dragged and drop in one go. This feature will be very useful when there is a remote site that can not place the documents in the right TMF hierarchy. Such remote sites can upload all the documents into a TEMP directory into the system and later the central coordinator/CTA or CRA can index the documents to the right TMF structure.

5. Automated Version Controlling:

The system should be capable of tracking each version of the document along with its description of changes every time a document is modified/ re-uploaded.

The system should be capable of having automated versioning based on the user edits and at the same time system should ensure only one user can modify the document at a given point in time to make sure every version of the document contains who has done what changes.

6. Electronic Signatures & Converting to PDF:

The system should be capable of capturing the electronic signatures of the authors, reviewers and approvers and print the same when it’s downloaded as PDF with inbuilt PDF conversion options. System should also be capable of printing configurable watermarks and the change descriptions along with electronic signatures.

If you want to have a 100% electronic TMF, then the signature technology also needs to meet the requirements of 21 CFR Part 11 electronic signatures when signing records.

7. External System Integration

The system should be able to integrate with CDMS/ CTMS systems to get the study, site, patient and other information and should be able to dynamically create Directory Structures and upload documents

8. Remote monitoring with Sharing and Collaboration

A good eTMF system should allow a user to invite external parties to upload and work collaboratively on a document system in a controlled method as it is essential for such systems to integrate and exchange information with one another.

9. Inspection Ready & Regulatory Compliance

The system should have Inventory and complete audit reports which can be shared with the Regulatory auditors during the audit which shall give complete overview and history on how the study documents are captured and filing in the eTMF repository.

The system should also maintain an audit trail for every operation and should have fully compliant eSignatures for all stakeholders.

It should also comply with all current and regulations including 21 CFR Part 11, ANNEX 11, GxP, and GDPR.

10. Advanced Analytics to track Completeness, Quality & Timeliness

The system should consist of interactive dashboards having analytics which will help business users to gain powerful and actionable insights. Importantly, the system should have dashboards to monitor the completeness of the study, Quality of the documents collected, and timeliness of the Study / Country / Site document filing and reviews.

Hope you found this article informative. Please reach out to arun.g@clinevotech.com, if you have any comments.

Pharmacovigilance has grown significantly in recent years and its importance in the healthcare sector has been recognized worldwide. To prevent or lower the patient hazards, improvements in public health and precise evaluation and monitoring of drug safety has become extremely important. This makes the need for a highly efficient Pharmacovigilance (PV) database essential for all the Pharma, Biotech, and Clinical Research Organizations.

Being a highly essential system in the life sciences sector, a PV database should be able to achieve maximum productivity at the same time keeping track of compliance where the humans can fail to complete the processes with accuracy and efficiency.

To obtain this kind of productivity and efficiency, you must keep in mind some of the essential features which a PV system should comprise.

1. The Must-Have Basic Features:

Below are some essential features that a pharmacovigilance database should have:

• The system should have the ability to report adverse events via configurable web form over secured internet.
• Custom validation should be present to ensure data consistency & completeness of cases.
• ICSRs – R2 & R3 compliance.
• Periodic Reports (like NDA, PADER, PSUR, etc.) and Line listings must be present.
• Must have an automated configuration for listedness.
• Auto narratives.
• Should support medical devices, clinical studies, spontaneous, literature cases, etc.
• MedDRA and WHO Drug dictionary integration
• The system should have more configurations and less customizations
• Must have an in-built AS2 gateway for regulatory e-submissions.

2. User Friendly and Easy-to-Use:

A PV database with a lot of advanced features without a user-friendly interface will gradually reduce the performance and the interest of the team and gradually impacts the timelines and the overall business.

3. Configurable to meet sponsor SOPs

The timelines of submission differ for each regulatory agency and sponsors. The SOPs differs from sponsor to sponsor. A PV database should be dynamic enough to be confirmed to address all the changing regulatory and sponsor needs with configurations. The system should not make the sponsor to change his SOP according to the system, but the system should be capable of meeting sponsor SOP and timelines.

Example:

The system should provide dynamic workflows to create different workflows for different types of cases (serious cases vs. non-serious vs. death cases). A company should be able to configure different timelines and different QC/MR process for a serious case and death case.

For a serious case, the admin should be able to set the duration of the complete process as 5 days – set 2 days for the completion of Data Entry, 1 day each for the other three processes, whereas he can set a 15-day duration for a non-serious case and can assign 4 days for Data Entry, 4 days for Quality Review, 4 days for Medical Review, 3 days for Reporting or whatever sequence he requires. Similarly, he can assign the 4 days to the serious and death cases giving 1 day each for every process and so on.

4. Automated Case Tracking / Monitoring Case Submission Timelines

Meeting timelines of the regulatory is a crucial task in Pharmacovigilance. When the number of cases increases, it becomes hard for the CROs/ Pharma companies to track every case to ensure it is processed and submitted to agencies on time.

PV database should be capable of assigning timelines for the cases based on the sponsor / regulatory timelines and track the cases to ensure it is submitted to regulatory agencies on time. The feature should allow the system to give intimation in the form of an automated email to the concerned personnel about the due dates and sends follow-ups if the case has not been dealt with within the required time period.

5. Regulatory Compliance and Inspection Ready

6. Should be Cost-Effective:

Pharmacovigilance is an expense for any company. Some Pharma/CROs on the verge of saving costs, they cut the costs on the teams they hire, and they spend a lot on procuring traditional Pharmacovigilance databases. This strategy is completely wrong. Just an expensive PV system cannot meet all the regulatory guidelines without a strong team in place.

7. Website and Call Centre ADRs / MI / PQCs

With the changing regulatory guidelines and increasing regulations, it is important to completely get rid of any information that is tracked out of the Pharmacovigilance databases.

ADRs are generally completely processed and tracked in the Pharmacovigilance database. But most of the PV databases does not support capturing and tracking of the medical inquiries and product quality complaints. Since the MI, PQCs and ADRs goes hand in hand, the Pharmacovigilance database should support handling of MIs and PQCs as well. Pharmacovigilance database should also support receiving the ADRs, MIs and PQCs directly from the Sponsor websites and Sponsor / CRO call centres.

8. AI & Automation

9. Multilingual Capabilities

There is a growing urgent need for accuracy in translation of clinical documentation and reporting; from pre-marketing clinical testing, adverse event / Pharmacovigilance reporting, coding and word-to-word documentation. For some regulators, there is a requirement for the data to be processed and reported in their local language.

For countries like Japan and China, new rules for Pharmacovigilance are on the way. CROs, Biotech and Pharma companies from these countries will soon be required to submit their regulatory reports in their national languages by the end of 2020.

The existing traditional systems can only support English as the language and even if some systems have the capability to provide a setup for any other language such as Chinese, Japanese, etc. or can convert a language into another, they tend to charge a substantial cost for the same.

Multilingual system would also be of great use as the local Pharmacovigilance employs of these countries can complete all the processes efficiently and in little time when provided with an ease of their local language on the PV systems.

Not only in Japan and China, but multilingual PV systems would be extremely beneficial to all the countries in all parts of the world hence the Pharmacovigilance database should be multilingual.

10. Signal Detection

As manual signal detection processes consume considerable time, PV team might require a few weeks to analyse a signal. The system should have an in-built signal detection feature as the PV team require focusing on real-time issues while reducing the time and effort spent in determining the fake signals. Hence it is important that the PV database supports signal detection.

Hope you found this article informative. Please reach out to prasanna.g@clinevotech.com, if you have any comments.

Pharmacovigilance, also known as drug safety, is the pharmacological science relating to the collection, detection, assessment, monitoring, and prevention of adverse effects with pharmaceutical products.

Pharmacovigilance being an extensive part of healthcare and clinical trials requires the combination of deep understanding of medical translation with the intricacies of clinical research, marketing and reporting. Some countries have made the reporting in their local language mandatory.

The Need for Multilingualism in Pharmacovigilance

There’s a growing urgent need for accuracy in translation of clinical documentation and reporting; from pre-marketing clinical testing, adverse event / pharmacovigilance reporting, coding and word-to-word documentation. For some regulators, there is a requirement for the data to be processed and reported in their local language.

For countries like Japan and China, new rules for pharmacovigilance are on the way. CROs, biotech and pharma companies from these countries will soon be required to submit their regulatory reports in their national languages by the end of 2020.

The existing traditional systems can only support English as the language and even if some systems have the capability to provide a setup for any other language such as Chinese, Japanese, etc. or can convert a language into another, they tend to charge a substantial cost for the same.

Multilingual system would also be of great use as the local pharmacovigilance employs of these countries can complete all the processes efficiently and in little time when provided with an ease of their local language on the PV systems.

Not only in Japan and China, but multilingual PV systems would be extremely beneficial to all the countries in all parts of the world.

Clinevo Safety & It’s Multilingual Capabilities

Clinevo Safety is a cloud based, user-friendly, easy to use, regulatory compliant end to end Pharmacovigilance / Drug safety system. All-in-one system provides PV Intake, Case processing, Regulatory submissions / AS2 gateway, Analytics, and Safety signals capabilities under one platform.

It is supported by technology that enables quick turnaround of your specialist requirements. Clinevo Safety can process data in any language like German, Japanese, Chinese, etc. The complete system gets adopted to any language with just an admin configuration.

Apart from just multilingualism, Clinevo Safety also offers dual language support where all the text is available in two different languages and these languages can be set according to the user preference. The multilingual and dual language capability of Clinevo Safety makes it a language friendly, efficient and cost-effective multilingual global system.

Data collected in clinical trials are complex, vast and growing uncontrollably with the number of clinical studies, clinical research softwares and vendors present in the clinical research market. For one study, a Clinical research company must work with several different vendors and software including

• CDM/EDC Systems (like Oracle Clinical/RDC, Inform, RAVE, Open Clinica, Clinevo EDC etc.)
• Safety Systems (like Argus, ArisG, Clinevo Safety, etc.)
• CTMS Systems (like Siebel Clinical, Clintrace, Clinevo CTMS)
• SAS-Based Systems
• Cloud-Based Systems
• Legacy Systems
• Spreadsheets
• Local and Central Lab Systems
• EMR/EHR Systems
• Regulatory Submission Systems.

Can you store, access and interact with all your clinical trial data in one place?

Data from all these different systems/sources being in different formats, makes impossible to get all the data in one place.!

What is a Clinical Data Warehouse?

A Clinical Data Warehouse or a Clinical Data Repository is a real-time database that consolidates data from a variety of clinical, safety and non-clinical sources to present a unified view.

All the data like Clinical Data, Operations Data, Safety Data, Lab Data and other data of one study can be available in one place for review, reporting and analytics. A Business intelligence tool in combination with a Data warehouse can enable you to know the progress of the trial in real time and enables you to monitor and take right decisions at the right time.

• Storage
• Review
• Standardization
• Aggregation
• Analysis
• Submission

Data warehousing enables you to perform

• Cross study analysis
• Data harmonization
• Data reconciliation
• Data recording
• SDTM transformation
• Data Aggregation and
• any business processes

Purpose of a Clinical Data Warehouse:

Purpose of Clinical Data Warehouse lies somewhere in its definition itself i.e. a database created by combining data that is gathered through various sources that can be of different types and formats (e.g. oracle, SAS, text, sql, xml etc.).

In a nutshell, Data Warehouse is a process of collecting data, transforming it, loading into single database and then using a BI (Business Intelligence) tool to answer your analytical queries and prediction of any further questions that may arise are helpful to your domain or business.

Benefits of a Clinical Data Warehouse:

Below are a few benefits of implementing a Clinical Data Warehouse for your Clinical Trials:

1. Improving Visibility of Data / All-in-One Platform:Clinical research organizations process data in different systems, which support the various business processes. In order to create an overall picture of clinical, operations, safety, non-clinical, lab and other data for sponsors and CROs – thus creating a single version of the truth – the data must come together in one place and made compatible. Both external (from the environment) and internal data (from various systems) should merge into the data warehouse and then be grouped. Therefore, having a single source to answers all your queries.
2. Improved Performance: One could use an already existing operational database if there is only single database for all the data, yet there few constraints like performance which degrade for both operational processes and reporting processes. Therefore, we create a database tuned and optimized database which will be ready to answer queries which require to bring huge amount of data and analysis.
3. Increase Data Quality: Users frequently overestimate the quality of data in the source systems. Unfortunately, source systems often contain data of poor quality. When we use a data warehouse, we can greatly improve the data quality, either through – were possible – correcting the data whilst loading or by tackling the problem at its source.
4. Faster Decision Making and More advanced Reporting: The structure of both data warehouses enables end users to report in a flexible manner and to quickly perform interactive analysis based on various predefined angles. They may, for example, with a single mouse click jump from year level – to quarter – to month level and quickly switch between the clinical data and the operational data whereby the indicator remains fixed. In this way, end users can juggle with the data and thus quickly gain knowledge about business operations and KPIs (Key Performance Indicator). Some metrics like – Which Site is not performing well? Which Investigator is not performing? Which patient is not regular for trials? Can be zeroed in in no time to find out the bottle necks of a trial and take necessary action time to avoid delays in the trails because of non-performing factors.
5. Regulatory Compliance: Clinical data warehouse stores audits of every action and stores data snapshot of data of different timestamps and provides version controls for the loads and programs which can help convincing the auditors on the data security, data handling and single source of truth.

About Clinevo Data Warehouse:

Clinevo Data Warehouse is an easy to use, secured, regulatory compliance clinical trials data repository & warehouse to acquire, store, transform, consolidate and report diverse data of clinical trials in one place.

Features of Clinevo Data Warehouse:

1. One Clinical Data Repository:
   • Holistic view of all clinical, safety and operational data of a clinical trial in one place
2. Wide Range of Tech Type Integrations:
   • Oracle, SAS, Text/CSV, XML, SQL Server, web services Imports
   • Oracle PL/SQL and SAS programs
   • SAS, TEXT, XML, Oracle Extracts
3. Inbuilt Business Process
   • Data Harmonization – Harmonize data from different source structure to one target structure
   • Data pooling – To the database schema (or) to remote DB with security
   • Data masking – supports various approaches
4. Increased Efficiency and Automation
   • Robust incremental refresh to get the data refreshed within 4 hours from a heavy Source system
   • Incremental data refresh for non-primary key tables
   • Incremental data refresh based on data element group
   • Parallel Data Loading
   • Configurable Automated Data Loads
5. Clinical Metadata Repository (MDR) Integration
   • Any Clinical MDR systems (COTS) or Legacy systems can be integrated with CLIDAC directly (or) thru web services to get the metadata.
6. Audit/ Regulatory Compliant
   • 21CFR part 11 regulatory compliance
   • Audit trail for every operation
   • Complete user tracking

Read more about the features of Clinevo Data Warehouse:

https://www.clinevotech.com/products/data-warehouse