1. Decentralized Clinical Trials (DCTs)

Decentralized clinical trials (DCTs) are transforming the traditional model by leveraging technology to conduct trials outside conventional clinical settings. This approach brings the study to the patient, utilizing digital health technologies, remote monitoring, and telemedicine to collect data.

Benefits:

• Increased Participation: DCTs reduce geographical barriers, enabling more diverse patient participation.
• Improved Patient Convenience: Participants can undergo assessments and provide data from the comfort of their homes, enhancing retention rates.
• Faster Recruitment: With broader reach, DCTs can accelerate participant recruitment, reducing trial timelines.

2. Advanced Data Analytics and Artificial Intelligence (AI)

The integration of advanced data analytics and artificial intelligence (AI) is revolutionizing how clinical trial data is collected, analyzed, and interpreted. These technologies enable researchers to uncover patterns and insights that were previously unattainable.

Applications:

• Predictive Analytics: AI can predict patient outcomes, optimize trial design, and identify potential risks early in the trial process.
• Real-Time Monitoring: Advanced analytics allow for continuous monitoring of patient data, ensuring timely intervention if adverse events occur.
• Data Integration: Combining data from various sources (e.g., electronic health records, wearable devices) provides a comprehensive view of patient health and trial progress.

3. Personalized Medicine and Precision Trials

The shift towards personalized medicine is driving the development of precision trials, where treatments are tailored to individual patient profiles based on genetic, biomarker, phenotypic, or psychosocial characteristics.

Key Aspects:

• Targeted Therapies: Trials are increasingly focusing on specific patient subgroups most likely to benefit from the intervention.
• Biomarker-Driven Studies: Identifying and utilizing biomarkers for patient selection and treatment efficacy assessment.
• Adaptive Trial Designs: These designs allow modifications based on interim results, improving trial efficiency and success rates.

4. Patient-Centric Approaches

A growing emphasis on patient-centric approaches ensures that trials are designed and conducted with the participant’s needs and experiences in mind. This trend recognizes patients as partners rather than subjects.

Strategies:

• Enhanced Communication: Transparent and ongoing communication with participants about trial progress and findings.
• Patient Advocacy Involvement: Involving patient advocacy groups in trial design to ensure relevance and improve patient engagement.
• Flexible Protocols: Designing protocols that accommodate patients’ lifestyles and reduce the burden of participation.

Blockchain for Data Security and Transparency

The use of blockchain technology in clinical trials offers enhanced security, transparency, and traceability of data. This technology addresses many challenges associated with data integrity and regulatory compliance.

Advantages:

• Immutable Records: Blockchain provides an unalterable ledger of all trial activities, ensuring data integrity and trustworthiness.
• Enhanced Privacy: Secure data sharing while maintaining patient confidentiality.
• Regulatory Compliance: Facilitates adherence to regulatory requirements by providing transparent and verifiable data trails.

6. Increased Focus on Rare Diseases and Orphan Drugs

There is a heightened focus on developing treatments for rare diseases and orphan drugs. Advances in genetics and molecular biology enable the identification of disease mechanisms and potential therapeutic targets for these conditions.

Developments:

• Collaborative Research: Partnerships between academia, industry, and patient organizations to pool resources and expertise.
• Regulatory Support: Incentives and support from regulatory bodies to expedite the development and approval of treatments for rare diseases.
• Innovative Trial Designs: Use of innovative trial methodologies, such as platform trials and basket trials, to evaluate multiple therapies simultaneously.

7. Virtual and Augmented Reality (VR/AR)

Virtual reality (VR) and augmented reality (AR) are emerging tools in clinical trials, offering novel ways to enhance patient engagement and training for clinical staff.

Applications:

• Patient Education: VR/AR can provide immersive educational experiences, helping patients understand trial procedures and expectations.
• Simulation Training: Training for clinical staff using VR simulations to improve protocol adherence and patient interactions.
• Pain and Stress Management: VR applications to manage patient pain and anxiety during procedures.

8. Regulatory Evolution

Regulatory agencies worldwide are adapting to the changing landscape of clinical trials by introducing flexible and adaptive regulatory frameworks. These changes aim to facilitate innovation while ensuring patient safety and data integrity.

Regulatory Trends:

• Guidance on DCTs: Development of guidelines to support the implementation of decentralized trials.
• Adaptive Design Acceptance: Increased acceptance of adaptive trial designs to accelerate development timelines.
• Real-World Evidence (RWE): Encouraging the use of real-world evidence to supplement traditional clinical trial data for regulatory decisions.

Conclusion

The next five years promise significant advancements in clinical trials, driven by technology, personalized medicine, patient-centric approaches, and regulatory evolution. These trends are poised to enhance the efficiency, accuracy, and inclusivity of clinical research, ultimately leading to the development of better treatments and improved patient outcomes. By embracing these innovations, the clinical trial industry is set to transform and meet the challenges of modern healthcare.

About Astrix

Astrix is the unrivaled market-leader in creating & delivering innovative strategies, solutions, and people to the life science community.  Through world class people, process, and technology, Astrix works with clients to fundamentally improve business & scientific outcomes and the quality of life everywhere. Founded by scientists to solve the unique challenges of the life science community, Astrix offers a growing array of strategic, technical, and staffing services designed to deliver value to clients across
their organizations.

The post Clinical Trials: Trends to Watch For In Next 5 Years appeared first on Astrix.

Typically, you can find the SoA located on a few pages in a clinical trial protocol created on a word document. It appears in a table that creates a chronological visit outline and specific checklist of each assessment expected at that visit. Further detailed information about each visit and assessment not included in the table is often found in embedded in the protocol in numerous different sections, in lengthy footnotes or appendices. In a digital SoA, every assessment or measurement is defined alongside industry standards with inclusion of what would be written in these footnotes or other sections of the protocol. Creating a digital SoA, combines this information into a searchable format and eliminates manual review across different sections of the protocol, reducing the risk for missed required datapoints. Every assessment or measurement used in protocol design that was created in the digital SoA platform, would be defined universally enhancing the understanding of what is to be expected out of that requirement and laying the foundation for a Digital Protocol.

Furthermore, sponsors and study teams, even within an organization, often  refer to the same specific assessment by different names. Within a digital SoA, a standardized language is employed allowing for easier communication and shared understanding across key stakeholders, improved interoperability with downstream consumers of the SoA content, and streamlined updates for protocol amendments. For example, the digital SoA can quickly be updated from standardized information as amendments are approved, minimizing the room for error, protocol deviations, and missed system updates. Research staff and Clinical operations teams can refer to a single source of truth that holds all relevant information and rely on its accuracy to guide their practices.

This standardization also drives enhanced data management, one of the most prominent areas in clinical trials that can benefit from a digital SoA. Traditionally, electronic data capture (EDC) systems are created by a Data Manager that reviews the SoA document and translates it into defined system requirements and specific data standards³. This digitized information removes the need for translation and sets the stage for automation to associate the assessments listed in the SoA with the comparable data standards, system requirements and data collection forms³. EDC can be developed in direct accordance with the protocol requirements within every patient visit. Navigation within those EDC platforms would directly correlate with the protocol, in a user-friendly platform. Digital SoA takes a traditionally time consuming, tedious process and streamlines it to benefit data collection across the trial. Further, a digital SoA promotes a data driven design by its ability to provide real-time insights on decisions made by Data Managers or research staff. For example, a digital SoA can provide a snapshot of a what data would be impacted if a lab assessment is missed. Data snapshot abilities can reduce the burden on a Data Manager, allowing users togenerate queries showing the impact of different decisions and scenarios prior to them occurring. A study team can guide their decisions for each patient based upon real-time, real-world data and see the risks, safety information, patient overviews, data impacts, etc. that each decision may cause.

Additionally, data management teams need consistency. The information found within a digital SoA is reusable for future protocols and creates standardized repeatable workflows such as downstream integrations and document generation⁴. Interoperability is improved through standardization using a consistent data model such as USDM (Unified Study Definition Model) supported by industry standards (e.g., ICH M11: Clinical electronic Structured Harmonized Protocol (CeSHarP)⁵ , CDISC controlled terminology⁶, etc.)As each assessment and measurement is defined, this consistency in data model and terminology allows information to more easily flow downstream across platforms and documents like EDC, CTMS, IRT, lab manuals, etc. bridging the gap between systems and reducing manual effort for the study. All in all, a digital SoA supports the data management process, while maintaining improved efficiency and accuracy in trials.

The concept of turning a clinical trial “digital” is no stranger to researchers. Technology has continually changed the face of clinical trials and overcome challenges through its developments. The benefits that are seen can be endless – processes have been streamlined, costs are reduced, patient data is better obtained and protected, accuracy and ability to adhere to protocols are improved, etc. Implementing a digital SoA is just one of those impressive developments. The SoA carries the weight of success for researchers, therefore, its development into something more is important to consider as the field continues to further digitize and embrace technology.

References

1. Tufts Center for the Study of Drug Development. Impact Reports – Rising Protocol Design Complexity is Driving Rapid Growth in Clinical Trial Data. csddtuftsedu. 2021;23(1). https://csdd.tufts.edu/impact-reports.
2. Ken Getz, M.B.A. K. Shining a Light on the Inefficiencies in Amendment Implementation. wwwappliedclinicaltrialsonlinecom. 2023;32(12). https://www.appliedclinicaltrialsonline.com/view/shining-a-light-on-the-inefficiencies-in-amendment-implementation
3. Georgieff T. Navigating toward a Digital Clinical Trial Protocol. wwwappliedclinicaltrialsonlinecom. 2023;32(12). Accessed May 3, 2024. https://www.appliedclinicaltrialsonline.com/view/navigating-toward-a-digital-clinical-trial-protocol
4. XTalks – Faro Health Inc. Clinical Data Management Insights: Using Digital SoA to Solve Modern Clinical Trial Challenges. Xtalks. Published August 24, 2023. Accessed May 7, 2024. https://xtalks.com/webinars/clinical-data-management-insights-using-digital-soa-to-solve-modern-clinical-trial-challenges/.
5. International Council for Harmonisation of Technical Requirements. ICH M11: Clinical Electronic Structured Harmonised Protocol (CeSHarP) FDA and Health Canada Regional ICH Consultation.; 2023. Accessed May 7, 2024. https://www.fda.gov/media/167334/download.
6. CDISC Digital Data Flow for Clinical Trial Protocols. Accessed June 21, 2024 https://www.cdisc.org/ddf

About Astrix

Astrix is the unrivaled market-leader in creating & delivering innovative strategies, solutions, and people to the life science community.  Through world class people, process, and technology, Astrix works with clients to fundamentally improve business & scientific outcomes and the quality of life everywhere. Founded by scientists to solve the unique challenges of the life science community, Astrix offers a growing array of strategic, technical, and staffing services designed to deliver value to clients across
their organizations.

The post The Benefits of Implementing Digitized SoA in Clinical Research Protocols appeared first on Astrix.

Artificial Intelligence and Machine Learning Generation

By no surprise, Artificial Intelligence and Machine Learning is at the top of the list. AI and ML are continually evolving processes that are beginning to prove a sustainable effort in optimizing clinical research efforts. AI and ML models are being piloted to see what areas of clinical research will benefit the most. In an article published by Health and Technology (2023), 5 areas of clinical research are described with potential benefits from AI and ML – preclinical, design, recruitment, conduct and analysis. In a preclinical stage, AI and ML can highlight unmet medical needs by accessing previous preclinical and clinical research datasets, as well as toxicity data to predict safety outcomes and develop models with applicable treatments. Another example is within recruitment, which remains a complex process in clinical research. AI and ML have the ability to comprehend inclusion and exclusion criteria and cross-reference demographics, laboratory numbers, imaging reports, therapeutics, etc. that correlates a patient with a specific trial. With such beneficial potential of AI and ML, clinical trial regulation will continue to develop with inclusion of these topics.

Improvement upon Global Harmonization 

There is an increased push for global harmonization across clinical research. The access and conduction of global clinical trials is important for generalizability in the field. The need for technology that suits globalization by being applicable and usable across trials is evident. Data harmonization is a great place to start. For example, a technology trend to keep an eye out for that supports this push are platforms that ensure standardized data formats, security, shareability and increased data protections. This type of platform promotes the consistency within data and makes it available across countries.

Normalizing Decentralized Trials

Decentralized Clinical Trials are at the forefront of clinical research and have been since the COVID-19 pandemic. Their popularity has continued to grow over the last few years. DCT allows for reach across the population, which promotes diversity in a trial. It has been repeatedly cited that less than 5% of eligible patients participate in clinical trials (Murthy et al., 2004). Virtual telehealth visits, remote data collection and wearable devices allow for subjects who are not located near traditional research sites to participate more conveniently, provide direct real-time data, and improve engagement in the clinical trial. Simply put, they better serve clinical research patients. In 2024, we would expect to see regulations from entities, such as the FDA and EMEA, continue to be developed in regard to DCT and what digitized components are allowed.

Inclusion of Advanced Digital Biomarkers

Digital biomarkers are a technological output that we may see used more within clinical research in the coming year. As we previously mentioned, DCTs can include wearable devices to continuously track specific endpoints, but these types of biomarkers can be applied within your traditional trials as well. Digital biomarkers are measured across layers of hardware, that include wearable, implantable and digestible devices that are used in a participant’s home collecting data that may be impossible to obtain in the clinic (Byrom et al., 2018). These devices can impact the results that clinical trials produce with key data points, personalization, treatment suggestions and disease trend tracking. It will not be surprising to see improving accuracy and precision in the data they produce in the year to come.

Blockchain Technology Implementation

In 2024, you can expect a rise in blockchain technology in clinical research. This technology allows for enhanced audit trails and record tracking, while changing the way that patient data is protected. The integrity and quality of a clinical trial can be undermined in the case of tampering, error or misconduct. It leaves the public with a sense of distrust towards the field. Blockchain technology is the solution. Dr. Natalia Sofia, MSc. (2023) explains that blockchain technology provides highly secure, time-stamped audit trials that play a pivotal role in ensuring reliability and coherence within systems for more informed decision-making regarding clinical trials. The honest facilitation and access address the demanding concerns that come from sensitive data security (De Novi, et al., 2023).

About Astrix

Astrix is the unrivaled market-leader in creating & delivering innovative strategies, solutions, and people to the life science community.  Through world class people, process, and technology, Astrix works with clients to fundamentally improve business & scientific outcomes and the quality of life everywhere. Founded by scientists to solve the unique challenges of the life science community, Astrix offers a growing array of strategic, technical, and staffing services designed to deliver value to clients across
their organizations.

References

• Askin, S., Burkhalter, D., Calado, G., & El Dakrouni, S. (2023). Artificial Intelligence Applied to clinical trials: opportunities and challenges. Health and technology, 13(2), 203–213.

• Byrom, B., Watson, C., DPhil, H., Coons, S., Eremenco, S., Ballinger, R., McCarthy, M., Crescioni, M., O’Donohoe, P., & Howry, C. (2018). Selection of and Evidentiary Considerations for Wearable Devices and Their Measurements for Use in Regulatory Decision Making: Recommendations from the ePRO Consortium. Value in Health, 21(6), 631–639.

• De Novi, G., Sofia, N., Vasiliu-Feltes, I., Yan Zang, C., & Ricotta, F. (2023). Blockchain Technology Predictions 2024: Transformations in Healthcare, Patient Identity, and Public Health. Blockchain in healthcare today, 6,

• Motahari-Nezhad, H., Fgaier, M., Abid, M. M., Péntek, M., Gulácsi, L., & Zrubka, Z. (2022). Digital Biomarker–Based Studies: Scoping Review of Systematic Reviews. JMIR MHealth and UHealth, 10(10), e35722.

• Murthy, V. H., Krumholz, H. M., & Gross, C. P. (2004). Participation in Cancer Clinical Trials. JAMA, 291(22), 2720.

The post Top 5 Technology Trends to Keep an Eye on in Clinical Research in 2024 appeared first on Astrix.

Pharmaceutical companies with which we’ve worked can find it a heavy lift to complete and streamline the seemingly myriad of tasks. We’ve seen efforts encounter challenges, due to a lack of consideration and coordination among multiple, related organizations.

In this podcast RIM expert, Heather Adinolfi discusses the strategies and tactics that can effectively:

• Identify and anticipate common hurdles,
• Mitigate the impact of common unavoidable challenges, and
• Smooth the road to success with Regulatory Information Management.

Click below to listen to the podcast

The post Astrix Podcast – Insights to Succeed Throughout the Regulatory Information Management (RIM) Journey appeared first on Astrix.

With greater emphasis on patient centricity, it’s increasingly important to engage with them in the digital landscape. Finding ways to meet patients where they are to better engage with and educated them through their entire care journey.

Is digital data capture tied to patient-centric approaches for the design and execution of clinical trials. A DPE platform is an intuitive digital application that can be utilized by healthcare organizations and patients as a means to monitor pre- and post-operative care. This platform should be incorporated into the patient engagement strategy.¹

Digital patient engagement brings together multiple technologies (remote data capture via devices, use of eSource, etc.). This supports the emphasis on patient-centric trial approaches to enroll, educate, and to more quickly analyze and use results in trials across the ecosystem.

Benefits of Digital Patient Engagement

There are several benefits of leveraging Digital Patient Engagement.

• For the patient, this patient-centric approach to clinical trial design and conduct addresses patient needs that go unmet in traditional trial methods. Technology approaches using telehealth, total experience (TX), digital communications and engagement help to support the entire patient experience. These technologies are being used to support patient reported outcomes, digital biomarkers and endpoints, remote patient monitoring and testing, patient education, and electronic informed consent
• For the Sponsor the benefits include:
  • Accelerating clinical development
  • Enabling more representative patient access, gathering data directly from patients that would not otherwise be captured
  • Developing a more robust evidence package than traditional trials

Industry Trends

• Decentralized Trial (DCT) approaches are rapidly gaining traction. This is partially driven by COVID, making patient-centric and site-centric approaches, including direct to patient supplies, remote assessments, telemedicine, at-home sample collection, point of care assays and other means of collecting patient data faster.
• Digital patient engagement is increasing. This is happening through linking to social media and patient communities for improved demographics and enrollment, to the use of telehealth to connect with and educate patients and physicians, to supporting tracking, monitoring, to receiving data sooner and more reliable data collection and ingestion.
• Move towards rapid collection of more granular and rich data. Leveraging digital biomarker and endpoints for faster medical and safety assessments, adaptive trial design, and exploratory and translational research

Considerations with DPE

The ability to collect patient information and results more rapidly, and with richer datasets, enables better inputs for clinical, translational and exploratory research using data that extends from “bench to bedside”. There are however several factors to consider with DPE.

Requirement for a Technical Framework to collect patient data

• The need to establish technical capabilities (e.g., devices, apps, data transfer, etc.) keeping user experience in mind to enable patient research to collect patient data and endpoints. This in support of data driven innovation (in clinical, translational and exploratory) while assuring secure interactions, including identifying confirmation and protection.
• Establishment of a core common product platform and the continual assessment of changes in the marketplace to ensure cutting edge technologies are being leveraged.
• Introduction of core product integrations where relevant including advanced technologies.
• Different technologies may be used separately or combined to deliver capabilities in the Digital patient experience space such as:
  • Semantic and context sensitive graphical interfaces for patient facing systems
  • Touch interfaces on devices, wearables, data collection applications, etc.
  • Voice interfaces, chatbots and personal AI-assistants

Data Governance and Regulation

• The need to enable Dynamic Data Masking (DDM)¹ to mask any patient sensitive data based on HIPAA and other regulations.
• Incorporation of verification method for the availability of patient consent and expiration date if required.
• Deepen understanding of mechanisms of action through digital twins for the design of precision medicine.
• The need to utilize social media and mHealth technologies to improve recruiting, screening, enrollment and retention of patients in clinical trials.
• Enablement of clinical and translational to rapidly access and use relevant clinical data in work.

Why It Matters to You

An increased emphasis is now being placed on the Life Science industry to be patient centric. The intention is to find ways to meet patients where they are; making it easy for patients to engage in the process and educate them through their entire care journey. Life Science organizations are turning to Digital Patient Engagement Platforms to engage with patients digitally.

In this blog post we discussed:

• What is Digital Patient Engagement.
• Benefits of Digital Patient Engagement.
• Industry Trends regarding this area.
• Key Considerations when looking to deploy a strategy

About Astrix

Astrix is the unrivaled market-leader in creating & delivering innovative strategies, solutions, and people to the life science community.  Through world class people, process, and technology, Astrix works with clients to fundamentally improve business & scientific outcomes and the quality of life everywhere. Founded by scientists to solve the unique challenges of the life science community, Astrix offers a growing array of strategic, technical, and staffing services designed to deliver value to clients across their organizations

The post Digital Patient Engagement and Its Impact on a Digital Transformation of Life Sciences appeared first on Astrix.

In the years following the creation of Part 11, there was much discussion and confusion in the pharmaceutical industry regarding what it meant and how it would be enforced. Additionally, concerns were raised by many in the industry that the new regulation would significantly increase the cost of compliance and discourage innovation and technological advances. In response to these issues, the FDA released a guidance document in 2003 entitled “Part 11, Electronic Records; Electronic Signatures – Scope and Application,” which was intended to provide a practical interpretation of Part 11 and clear up industry confusion around its interpretation and enforcement. This guidance document clarified that the Agency intended to interpret the scope of part 11 narrowly and exercise enforcement discretion with regard to part 11 requirements for validation, audit trails, record retention, and record copying.

In the years since the 2003 guidance document was issued, there has been significant technological advances (e.g., cloud computing, mobile devices, etc.), and a proliferation of third-party vendors offering services for electronic systems. In order to address some of the questions that have arisen regarding Part 11 regulations due to the ongoing digitization of data in clinical trials, the FDA issued a draft guidance for industry titled “Use of Electronic Records and Electronic Signatures in Clinical Investigations Under 21 CFR Part 11 – Questions and Answers” in June of 2017.

This most recent draft guidance on electronic records and signatures clarifies, updates and expands upon the recommendations related to clinical trials in the 2003 guidance, and provides information to sponsors, institutional review boards (IRBs), clinical investigators, and clinical research organizations (CROs) on the use of electronic records and signatures in clinical trials conducted under 21 CFR parts 312 and 812. Let’s examine this new guidance document in detail in order to determine what it means for those involved in generating and signing electronic records in clinical investigations.

Scope of the FDA Guidance

In this new guidance document, the FDA affirms that it will continue to support a narrow and practical interpretation of Part 11, while at the same time reminding sponsors that electronic records must be maintained or submitted in a manner which satisfies all predicate rules. Additionally, this guidance clarifies and expands upon the policy announced in the 2003 part 11 guidance that encourages a “risk-based approach to the validation of electronic systems, implementation of electronic audit trails, and archiving of electronic records.”

This guidance document applies to electronic records and signatures in the following categories:

• Records kept in electronic format in lieu of paper that are required for clinical investigations of medical products. This includes all records that would be necessary for the FDA to reconstruct a study.
• Electronic records that are relied on to perform regulated clinical study activities.
• Records pertaining to clinical investigations that are submitted to FDA in electronic format under predicate rules, even if these records are not explicitly identified in FDA regulations.
• Electronic signatures required for clinical investigations that are intended to be the equivalent of handwritten signatures executed on paper.

The following electronic systems used in clinical investigations are addressed by the guidance in terms of their applicability to Part 11 requirements:

• Electronic systems, whether commercial off-the-shelf (COTS) or customized, that are owned or managed by sponsors and other regulated entities
• Electronic services that are outsourced by the sponsor or other regulated entities
• Electronic systems that are primarily used in the delivery of medical care
• Mobile technology and telecommunications systems

Overview of the FDA Guidance

The information communicated in this guidance document is extensive. The guidance provides 28 questions and answers (Q&A) detailing how sponsors, IRBs, clinical investigators, and CROs can ensure that electronic records and signatures are equivalent to paper ones and thus meet agency requirements. The bulk (24) of these Q&A cover the scope and application of Part 11 requirements in clinical investigations and are organized into 5 topics – Electronic Systems Owned or Managed by Sponsors and Other Regulated Entities, Outsourced Electronic Services, Electronic Systems Primarily Used in the Provision of Medical Care, Mobile Technology, Telecommunication Systems. A final section contains 4 Q&A that are dedicated to clarifying the appropriate use of Electronic Signatures.

Let’s look at some of the key expectations communicated by the guidance:

Electronic Systems Owned or Managed by Sponsors and Other Regulated Entities

The FDA lists a number of electronic systems used in clinical investigations that are owned or managed by sponsors or other regulated entities (e.g., CROs, IRBs) include: electronic case report forms (eCRFs), electronic data capture (EDC) systems, electronic trial master forms (eTMFs), electronic Clinical Data Management System (eCDMS), and others. Requirements and recommendations specified in this guidance for these systems include:

• Risk-Based Approach to Validation – Electronic systems should be validated if they are used to process/produce critical records that are submitted to the FDA. The FDA suggests a risk-based approach to validation, where the extent of validation varies from that which is defined by “internal business practice and needs” for off-the-shelf business tools in general use (e.g., word processors, spreadsheets, etc.), to “user acceptance testing, dynamic testing, and stress testing” for customized tools that have been developed to meet a unique business need. When determining the level of validation for a given system, sponsors and other regulated entities should consider the purpose and significance of the record (i.e., the extent of error that can be tolerated in the record without compromising its reliability and utility), and the attributes and intended use of the electronic system used to produce the record.
• FDA Inspections of Electronic Systems – The FDA will focus on documentation of system validation for both the implementation of these electronic systems, as well as any changes made (e.g., upgrades, security patches, new instrumentation, etc.) to the system once in use. Migrations of source data to other systems or formats will be checked to ensure that the data is not altered in value or meaning in the process. Additionally, the FDA will review standard operation procedures (SOPs) and support mechanisms (e.g., training, technical support, audits, etc.) to ensure that the system is being used and functioning in the manner intended.
• Vendor Audits – Sponsors and other regulated entities should use a risk-based approach in determining whether or not to perform vendor audits. To minimize time and cost burdens, the FDA suggests sponsors and other regulated entities consider “periodic, but shared audits conducted by trusted third parties.”
• Security Safeguards – In order to assure compliance with 21 CFR Part 11.10 and 11.30, sponsors and other regulated entities must ensure that procedures and processes are in place to limit access to the electronic systems utilized in clinical investigation to appropriate, authorized users. Additionally, external security safeguards (e.g., firewalls, anti-spyware, antivirus, etc.), need to be in place to prevent, detect and mitigate the effects of computer viruses, worms and other harmful software code on study data and software.
• Electronic Storage for Archiving Study-Related Records – Using a durable electronic storage device to archive a study-related record at the end of a clinical study is acceptable. Sponsors and other regulated entities should ensure that the content and meaning of the record and the integrity of the original data are preserved. If these records are archived in such a way that they can be searched, sorted, or analyzed, sponsors should provide electronic copies with the same capability to the FDA during an inspection if it is reasonable and technically feasible.
• Investigative Sites Outside the United States – The FDA states that if a non-U.S. site is conducting a clinical trial under an investigational new drug application (IND, then both the sponsor and the site must follow FDA regulations – Part 11 requirements will apply to any required records kept in electronic format.

Outsourced Electronic Services

When outsourcing electronic services (e.g., data management services, cloud computing services), sponsors and other regulated entities are ultimately responsible for ensuring that all regulatory requirements are met. As such, sponsors and other regulated entities need to ensure:

• the authenticity, reliability and security of any data used to support a marketing application for a medicinal product.
• that regulated records and data are available to FDA during an investigation or an inspection.
• that outsourced electronic services are validated when appropriate – documentation of SOPs and results for validation testing should be obtained from the outsourced electronic service vendor.

Sponsors and other regulated entities should form service agreements with any outsourced electronic service vendor, but before entering into such an agreement, the sponsor or other regulated entity should evaluate and select an electronic service vendor based on their ability to meet part 11 requirements and data security safeguards.

Sponsors and other regulated entities should be able to provide the following information to the FDA upon request at each of their regulated facilities that utilize outsourced electronic services:

• Specified requirements of the outsourced electronic service
• A service agreement defining what is expected from the electronic service vendor
• Procedures for the electronic service vendor to notify the sponsor or other regulated entity of changes and incidents with the service

Mobile Technology

The guidance document addresses the use of mobile devices in clinical trials, whether the device is provided by the sponsor or brought by the study participant. Mobile technology in this guidance document refers to portable electronic technology used in clinical trials that enables off-site, remote data capture from study participants – mobile platforms, mobile applications, wearable biosensors, and other portable, implantable and ingestible electronic devices. Requirements and recommendations specified in this guidance for mobile technology include:

• Access Controls – Sponsors should implement user access controls (e.g., ID code, username and password, electronic thumbprints, other biometrics) for mobile technology used by study participants in clinical trials to ensure that data entrees come from study participants. In cases where these controls are not practical, sponsors should obtain a signed declaration from study participants confirming that they will be the only ones using the device.
• Source Data – As mobile technology typically only stores data collected from study participants for a very short period of time before being transmitted to the sponsor, the FDA indicates that “…the first permanent record is located in the sponsor’s EDC system or the HER, and not in the mobile technology.”
• Validation of Mobile Technology – The guidance suggests a risk-based approach to validation of mobile technology. Sponsors should validate mobile technology before use in a clinical trial to ensure that a measured value is reliably captured, transmitted and recorded in the sponsor’s EDC system. Note that validation is specific to Part 11 and does not address performance of the mobile technology, which should follow standard medical device validation requirements.
• Audit Trails – When mobile technology is used to transfer data to the sponsor’s EDC system (or to the EHR and then the sponsor’s EDC), the audit trail begins at the time the data enters the sponsor’s EDC system. The EDC system should capture the date and time the data entered, as well as the data originator (study participant, mobile technology or EHR).
• Security Safeguards – Data transmitted wirelessly from a mobile device to a sponsor’s EDC must be encrypted both at rest and in transit to ensure confidentiality and prevent access by malicious parties. In addition to encryption and user access controls, sponsors should implement remote wiping and disabling of devices, firewalls, and procedures for wiping all stored health information on mobile devices before reusing or discarding to ensure confidentiality.
• Training – The FDA expects sponsors, clinical investigators, study personnel, and study participants to be adequately trained on the use of any mobile technology that is used in a clinical trial.

Electronic Signatures

To be considered the equivalent of handwritten signatures, electronic signatures must comply with Part 11 requirements. Nevertheless, in this guidance document, the FDA communicates flexibility in terms of the methods it will accept for the creation and verification of electronic signatures and biometrics.

• Methods of Creating Electronic Signatures – The Agency states that Part 11 allows for a wide variety of methods for creating electronic signatures – computer-readable ID cards, biometrics, digital signatures, and username/password combinations. All signatures on electronically signed documents need to be accompanied by a computer-generated, time-stamped audit trail.
• Verification of Identity of Those Who Create Electronic Signatures – Part 11 requires that organizations “verify the identity of an individual before the organization establishes, assigns, or otherwise sanctions an individual’s electronic signature or any element of such electronic signature.” However, the FDA does not specify any particular method for verifying the identity of an individual. Methods suggested include: birth certificate, government-issued passport, driver’s license, security questions.
• Biometrics – The FDA defines biometrics as “a method of verifying an individual’s identity based on measurements of the individual’s physical features or repeatable actions where those features and/or actions are both unique to that individual and measurable.” The FDA does not specify any particular biometric method upon which an individual’s signature should be based. Examples given as possible options include: fingerprints, hand geometry (i.e., finger lengths and palm size), iris patterns, retinal patterns, or voice prints.

In addition, the FDA provides important guidance regarding electronic signatures by an individual during a period of controlled system access: “When an individual logs into an electronic system using a username and password, it is not necessary to re-enter the username when an individual executes a series of signings during a single, continuous period of controlled system access. After a user has logged into a system using a unique username and password, all signatures during the period of controlled system access can be performed using the password alone.”

Conclusion

The information contained in the FDA’s new guidance document on electronic records and signatures is extensive, and signifies that the Agency is increasingly focused on data integrity in the electronic records submitted in support of new drug approvals. While this guidance is focused on electronic records and signatures in clinical trial documents, the concepts and recommendations outlined are applicable for any operational system that must conform to Part 11 requirements. Organizations would therefore be wise to consider the information communicated in this guidance document when implementing electronic records and signatures across the product lifecycle.

Additionally, partnering with a quality informatics consulting firm that specializes in data integrity and computer system validation in order to assess the status of your organization’s 21 CFR Part 11 compliance may be an effective path forward. Such a firm can help you define your  needs/requirements, and then determine the best business solution(s) that will bring your organization into regulatory compliance.

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