‍What is eCOA?

As FDA Principal Deputy Commissioner Janet Woodcock said in a 2015 Clinical Outcome Assessment Public Workshop, “It turns out that what is really bothering the patient and what is really bothering the doctor can be radically different things...patients are true experts in their disease.”

Clinical outcome assessments (COAs) have been key to capturing a comprehensive picture of patient experiences and treatment outcomes in today’s research landscape for decades. Integrating COAs into trial protocols bolsters our treatments' scientific integrity and enhances our ability to understand the real impact of interventions on patients. 

COAs (called eCOAs when captured electronically) are essential to understanding whether a drug reduces symptoms, improves patients’ quality of life, and improves their ability to perform activities they care about. 

Since the mid-2010s, electronic clinical solutions, like eCOA, have rapidly replaced their paper counterparts. Electronic Clinical Outcome Assessments comprise systematized digital methods for capturing patient-centered outcomes in clinical trials. These systems utilize validated electronic interfaces to collect, store, and analyze patient-reported data, clinician observations, and performance metrics.

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1. What are the different types of COAs

Electronic Patient-Reported Outcomes (ePRO)

ePROs facilitate direct data collection from study participants regarding their health status, symptomatic experiences, and quality of life metrics. These assessments employ validated questionnaires and standardized rating scales delivered through electronic platforms.

Electronic Clinician-Reported Outcomes (eClinRO)

eClinROs enable healthcare professionals to document clinical observations, physical examinations, and diagnostic assessments through structured digital formats, ensuring standardization across multiple study sites.

Electronic Observer-Reported Outcomes (eObsRO)

eObsROs provide mechanisms for non-clinical observers, such as caregivers, to record observable patient behaviors and functional capabilities through standardized electronic forms.

Electronic Performance Outcomes (ePerfO)

ePerfOs measure objective task performance through digitally administered assessments, capturing cognitive function, physical capabilities, and other quantifiable parameters.

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2. What are the benefits of eCOAs in clinical trials?

The proliferation of smartphones and digital devices has made electronic data collection the preferred method for gathering clinical outcome data, particularly patient-reported outcomes. This shift toward digital capture aligns with recommendations from regulatory bodies, including the FDA.

The well-documented benefits of using digital solutions to collect eCOA data, including ePROs, include:

‍Data integrity. eCOA can help ensure data collection follows the fundamental principles of data integrity as defined by Fthe DA: attributable, legible, contemporaneous, original and accurate, or ALCOA.

‍Data quality. With electronic data capture, researchers see enhanced data quality and accuracy, benefiting from real-time data flow and automation–for example, automatic calculations, branching to appropriate subsequent items, reducing missing data, and avoiding transcription of data-entry errors.

‍Patient-centricity. Patients can use familiar (or even their own) devices to answer surveys or participate in televisits from the comfort of their own homes. Plus, data may be automatically collected and transmitted via digital health devices. With this patient-centered approach comes a reduction in travel, meaning researchers can gain access to a more diverse patient population and studies see higher rates of compliance.

‍Better protocol compliance. On-device reminders or alerts, timestamped data entries, and programmed eCOA workflow help ensure assessments are completed in the order and/or during the times specified in the protocol.

Reduced patient and site burden. Study participants and site staff input their responses directly into the eCOA system, reducing data entry time and the need to keep assessment forms and paper diaries as source documents. 

‍ePROs: Transforming oncology research

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‍Simpler regulatory submissions. With cleaner, higher-quality data, sponsors can experience a greater increase in the ease of submissions, which contributes to the continuing regulatory agency guidance for these digital tools.

‍Remote data collection. The COVID-19 pandemic highlighted the need to include remote and digital solutions in the clinical trial process. As decentralized clinical trials (DCTs) become more common, the industry has recognized patient data can be collected via televisit and/or mobile app where appropriate, rather than always requiring on-site study visits. Reducing travel can reduce potential patient burden. In addition, remote data collection enables more frequent collection of data outside the clinical setting, enabling greater insight into the impact of the drug on the patient’s everyday life.

‍Better patient experience: eCOA connects users with extensive libraries of support materials, empowering them with up-to-date information on how to schedule a visit, how to use their devices, and answers to frequently asked questions. Ideally, participants should be able to access their trial information through their smartphone or tablet, with easier-to-consume supporting materials like videos present throughout.

‍Designing patient-friendly ePRO instruments

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‍Configurable reporting options. A robust reporting tool to connect with your eCOA system is a key advantage to DCTs. Electronic data capture solutions can help create an automatic series of questions with conditional responses. They may also reduce the complexity of possible reactions, an ability not easily obtained through paper surveys. Once created, eCOAs can be configured and deployed in numerous formats–providing further operational efficiencies.

‍Collaborative data creation and review. Electronic data capture solutions enable cross-functional groups to simultaneously create, review, and approve data. By deploying an ePRO solution, participants can quickly review and complete forms, providing high patient adherence and engagement.

‍Blog: How to design patient-friendly eCOA and ePRO instruments

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3. ‍What to consider when implementing an eCOA solution

When you’re ready to explore an eCOA solution, it’s important to consider the specific demands of the trial protocol, the patient and site staff experience, and regulatory requirements. Here are some things to consider: 

‍Design your eCOA solution to fit your protocol needs. As you consider the appropriate eCOA solution for your clinical trial, consider what data you need to collect, how that data will be collected, and the age and characteristics of your study participants (for example, their physical/cognitive abilities).

‍Consider where data collection will take place. Regardless of modality, remote eCOAs need to provide valid, reliable, and meaningful endpoints equivalent to on-site eCOAs.​eClinROs can be measured over a televisit or at site ePROs, and eObsROs can be measured on a mobile app or web application, at site or remotely

‍‍Think about your device strategy: provisioned or bring-your-own-device (BYOD). A BYOD model allows participants to use their smartphone or other device for data capture. When using a device with which they are already familiar, participants may be more likely to be compliant while not being burdened with multiple devices, ultimately leading to a better clinical trial experience. However, since some participants may be hesitant to download an app on their device or may not own a device that meets the requirements, it’s important to anticipate a percentage of provisioned devices, even in trials adopting a BYOD strategy.

‍Understand the regulatory requirements. The eCOA solution should align with the regulatory guidelines put forth by the U.S. Food & Drug Administration (FDA) and the European Medicines Agency (EMA) to ensure the reliability, quality, integrity, and traceability of electronic data. Other regulatory agencies may have additional guidance specific to the indication. 

‍ Align eCOA solution design with study timelines. When considering timelines concerns for eCOA development, the design of your eCOA solution should enable sufficient lead time and alignment with vendor project schedules. Launching a project too soon may provide a platform that is obsolete at the start of a study, while deploying a solution too late may delay the ability of some subjects to participate: creating operational inefficiencies.

‍Ensure training and support for sites and subjects. Successful eCOA systems include the right amount of quality training for sites and subjects, provide avenues for additional retraining to combat potential issues that may emerge, and offer a comprehensive help desk to provide critical support to participants. 

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4. Technical requirements of eCOA 

Robust eCOA must meet stringent technical requirements to ensure data integrity, security, and compliance. 

Key features and capabilities include:

  • Device compatibility: Support for various devices (iOS, Android, Windows) and operating systems. Responsive design for optimal user experience across different screen sizes.
  • Offline functionality: Ability to collect data even without internet connectivity, with secure synchronization when a connection is available.
  • Data security and compliance: Adherence to regulatory standards like 21 CFR Part 11, GDPR, and HIPAA. Robust encryption and access controls to protect sensitive patient data.
  • Integration capabilities: Seamless integration with other clinical trial systems, such as EDC (Electronic Data Capture) and CTMS (Clinical Trial Management System). APIs for data exchange and interoperability.
  • Workflow management: Features for managing study workflows, including participant enrollment, data collection schedules, and reminders.
  • Multilingual support: Ability to support multiple languages to facilitate global clinical trials.
  • Real-time data monitoring: Dashboards and reporting tools to monitor data quality and identify potential issues early on.
  • User-friendly interfaces: Intuitive and easy-to-navigate interface for patients, sites, and sponsors/CROs.

The eCOA implementation process

Implementing eCOA requires careful planning and execution. A typical implementation process involves the following steps:

  • Needs assessment: Define study objectives, data collection requirements, and target patient population.
  • Vendor selection: Evaluate different eCOA vendors based on their capabilities, experience, and cost.
  • System configuration: Customize the eCOA system to meet specific study requirements, including questionnaire design, workflow setup, and data validation rules.
  • Testing and validation: Thoroughly test the system to ensure data accuracy, functionality, and usability.
  • Training: Provide comprehensive training to study staff and patients on how to use the eCOA system.
  • Deployment: Deploy the eCOA system and begin data collection.
  • Ongoing support: Support study staff and patients throughout the duration of the study

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5. eCOA vs. Paper COA

Paper COA is prone to worse data collection

Simply put, paper Clinical Outcome Assessments (COAs) often fall short of meeting basic ALCOA (Attributable, Legible, Contemporaneous, Original, and Accurate) standards due to inherent limitations in their manual nature. 

Paper COAs are always at risk of failing to be attributable to the participant as they lack embedded attribution mechanisms, making it challenging to trace data back to its source reliably. Handwritten entries contribute to issues related to legibility, introducing the risk of misinterpretation and transcription errors. The contemporaneous nature is hindered by the delayed nature of data entry and the potential for retrospective completion, undermining the real-time aspect of data capture. Originality is jeopardized by the susceptibility to alterations, loss, or damage of paper documents during the course of a trial, most notably due to stains, ink smudges, tears, or missing items. 

Lastly, achieving true accuracy is impeded by the manual data entry process, increasing the likelihood of human errors and compromising the overall integrity of the data. In contrast, electronic Clinical Outcome Assessments (eCOAs) address these challenges by offering built-in features that align with ALCOA principles, ensuring data reliability, traceability, and integrity throughout the clinical trial process. 

A real-life example of this can be seen in the practice of “forward filling,” a practice where participants report completing paper diaries about their treatment outside of the required research windows. A 2002 study indicated that 45% of patients in a pain study forward-filled their data at least once ( “Patient Non-compliance with Paper Diaries,” Stone, A., British Medical Journal, 2002).

Better compliance lies within real-time data

Perhaps the greatest asset eCOAs can offer is real-time data, which enables better understanding, oversight, and decision-making for almost every facet of a trial. 

One of the primary advantages of real-time data in clinical trials is the ability to make prompt and informed decisions. With the continuous influx of data, researchers can identify trends, potential safety issues or concerns, and opportunities for trial improvement without delay.

This is in stark contrast to only receiving trial data and insights from participants at the time of their visits. 

Quality by design leads to better data

eCOAs not only streamline data collection but also foster better adherence from trial participants. Electronic interfaces can be designed with user-friendly features that unlock only when necessary, reducing the burden on participants and encouraging regular, familiar and accurate data input. 

‍Quality by design: How eCOA improves oversight and participant data quality

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Example: Guiding the participant’s journey

A sound eCOA system is built around guiding the participant naturally and seamlessly. 

Often, clinical trials may have tens to hundreds of activities for participants to complete throughout the trial, which can feel overwhelming for trial participants.Top-tier eCOAs help ease the experience of participation by releasing tasks one by one, prompting them only when they need to be completed.

For example, let’s imagine a participant must complete three trial activities daily, take their trial medication, complete a diary, and participate in a Televisit with their PI. Well-designed eCOAs will only unlock and prompt the participant to complete the necessary tasks at the time needed and provide notifications. Combined with psychosocial design, this helps guide the participant in a stressless, seamless way.

Example: Conditional question and branching logic capabilities

Let’s imagine a scenario where a participant is required to take study drug A if they’re experiencing headaches or study drug B if experiencing stomach aches. 

In this example, if a participant takes study drug A, then future diary questions are only geared towards collecting information related to drug A.

These question and branching logic capabilities are applied throughout all aspects of eCOA and the clinical trial, helping ensure better quality data at the point of entry. Additionally, the interactive nature of eCOAs allows for real-time validation checks, ensuring data completeness and accuracy. 

Example: Notifications and reminders

Notifications and reminders are pivotal in fostering improved medication and data adherence within clinical trials. Timely notifications are essential, reminding participants to take their prescribed medications consistently. This approach helps mitigate the risk of missed doses, contributing to more accurate and reliable data on the medication's efficacy. 

Additionally, participants are asked to log the time they took their study medication while also confirming the number of pills or doses they took and their actual shape and size. Participants are given images of their study drug and asked to verify that what they took matches what’s on screen.

Reminders tailored to participants' daily routines can enhance the overall patient experience, making adherence to medication schedules more manageable and less intrusive. Over time, the process becomes more intuitive and seamlessly integrated into their lives by aligning reminders with participants' habitual activities, such as daily routines or specific events. 

Electronic ease of use and “bring your own device”

Adopting eCOAs fosters a participant-centered approach by providing tools that better align with the modern technology experiences of their daily lives. Mobile applications and electronic devices make it easier for participants to engage with the study, leading to increased adherence to data collection protocols.

With the integration of “bring your own device” (BYOD), participants can use their smartphones, tablets, or other electronic devices to engage with the study. This approach recognizes and capitalizes on the prevalence of personal devices in individuals' lives, making participation more convenient and accessible and data submission much less cumbersome.

‍Creating success with digital measures

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6. Technical requirements and compliance

eCOA systems must comply with regulatory standards, including 21 CFR Part 11, HIPAA, and GDPR requirements while offering multi-platform compatibility across web, mobile, and tablet devices. Modern eCOA platforms provide comprehensive functionality, including offline data collection capabilities, automated validation processes, and real-time data synchronization, all supported by detailed audit trail documentation and electronic signature verification.

The technical capabilities of eCOA systems extend beyond basic data collection, encompassing sophisticated features such as multi-language support, configurable assessment scheduling, and automated reminder systems. These platforms facilitate real-time data monitoring, and many can seamlessly integrate with Electronic Data Capture (EDC) systems, allowing for the creation and implementation of custom forms and conditional logic. Exporting data in standardized formats ensures compatibility with a wide variety of analytical tools and regulatory submission requirements.

  • Device compatibility: Support for various devices (iOS, Android, Windows) and operating systems. Responsive design for optimal user experience across different screen sizes.
  • Offline functionality: Ability to collect data even without internet connectivity, with secure synchronization when a connection is available.
  • Data security and compliance: Adherence to regulatory standards like 21 CFR Part 11, GDPR, and HIPAA. Robust encryption and access controls to protect sensitive patient data.
  • Integration capabilities: Seamless integration with other clinical trial systems, such as EDC (Electronic Data Capture) and CTMS (Clinical Trial Management System). APIs for data exchange and interoperability.
  • Workflow Management: Features for managing study workflows, including participant enrollment, data collection schedules, and reminders.
  • Multilingual Support: Ability to support multiple languages to facilitate global clinical trials.
  • Real-time Data Monitoring: Dashboards and reporting tools to monitor data quality and identify potential issues early on.
  • User-Friendly Interface: Intuitive and easy-to-navigate interface for both patients and study staff.

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7. eCOA Implementation process

Implementing eCOA software requires careful planning and execution. A typical implementation process involves the following steps:

  • Needs assessment: Define study objectives, data collection requirements, and target patient population.
  • Vendor selection: Evaluate eCOA vendors based on their capabilities, experience, and cost.
  • System configuration: Customize the eCOA system to meet specific study requirements, including questionnaire design, workflow setup, and data validation rules.
  • Testing and validation: Thoroughly test the system to ensure data accuracy, functionality, and usability.
  • Training: Provide comprehensive training to study staff and patients on how to use the eCOA system.
  • Deployment: Deploy the eCOA system and begin data collection.
  • Ongoing support: Provide ongoing support to study staff and patients throughout the study.

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8. Future trends and innovations in eCOA 

The eCOA landscape is constantly evolving, with new trends and innovations emerging:

  • Wearable sensors and remote patient monitoring: Integration of wearable sensors and remote patient monitoring technologies to collect real-time physiological data.
  • Artificial intelligence and machine learning: Use of AI and machine learning to analyze eCOA data and identify patterns and insights.
  • Mobile health (mHealth) integration: Integration of eCOA with other mHealth apps and platforms.
  • Patient-centric design: Focus on creating more engaging and user-friendly eCOA experiences for patients.
  • Blockchain technology: Exploring the use of blockchain to enhance data security and transparency.

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9. Embracing eCOA, the future of patient-centric research

As we've explored, eCOA represents a paradigm shift in collecting and utilizing patient data in clinical trials. It's more than just a digital replacement for paper forms; it's a powerful tool that empowers patients, improves data quality, and accelerates the development of life-changing treatments. From enhanced data integrity and streamlined workflows to increased patient engagement and real-time insights, the advantages of eCOA are undeniable.

While challenges like technical implementation and user adoption exist, the industry is constantly innovating to address these hurdles. The future of eCOA is bright, with exciting developments like wearable sensor integration, AI-driven data analysis, and increasingly patient-centric designs on the horizon. By embracing eCOA and its evolving capabilities, we can unlock a new era of patient-centric research, ultimately leading to more effective and impactful healthcare solutions. We encourage you to explore available resources and consider how eCOA can transform your subsequent clinical trial.

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