Clinical outcome assessments (COAs) play a crucial role in oncology clinical trials, providing valuable patient-reported data on treatment efficacy, safety, and quality of life impacts. As the use of electronic COA (eCOA) solutions continues to grow, it is important for sponsors and Contract Research Organizations (CROs) to understand the unique challenges, opportunities and best practices for implementing eCOA in oncology studies.
This blog will explore key considerations for eCOA in oncology trials, common assessments used, and strategies for optimizing the patient and site experience.

The Role of eCOAs in Oncology Trials

Oncology is among the top therapeutic areas utilizing eCOAs across all study phases. While primary endpoints in oncology trials typically focus on objective measures like tumor size reduction and survival rates, COAs play a crucial role in supporting secondary and exploratory endpoints. In early phase studies, eCOA is primarily used to monitor dosing compliance and capture patient-reported toxicities. As trials progress to later phases, eCOA strategies expand to include broader quality of life measures associated with treatment and disease impacts. eCOA data collection in oncology tends to be less frequent and involves fewer assessments compared to other therapeutic areas. As a result, oncology eCOA implementations tend to be straightforward, low-complexity projects that can be executed quickly and efficiently.

That said, when designing eCOA strategies for oncology trials, it is essential to keep the patient population in mind. Oncology patients are often very ill and may suffer from fatigue, so COA approaches must be patient-centric and minimize burden while still collecting essential data. This balance requires a careful scientific approach to ensure appropriate questionnaire selection and administration schedule. An evidence based COA strategy able to withstand the rigor of the regulatory authorities should always be the end goal.

eCOA Implementation Considerations

When implementing eCOA in oncology trials, several factors must be considered:

1. Assessment strategy and schedule. Most protocols specify that COAs should be completed at clinic visits, prior to other assessments or procedures. The typical cadence is monthly during treatment, decreasing to every 3-6 months during later follow-up phases. Some protocols may allow a window for completion before or after visits, necessitating a flexible solution that enables patients to complete assessments from home.

2. Device provisioning strategy. For clinic-only assessments, site-based tablets are often sufficient. However, if any at-home completion is required, a Bring Your Own Device (BYOD) approach may be preferred. Additionally, eCOA systems should support caregiver logins and the ability to record whether the patient or caregiver entered the data, as some protocols allow for caregiver assistance with questionnaire completion.

3. Flexible Completion Windows. Given the health challenges faced by many oncology patients, it is crucial to choose an eCOA platform that allows patients to start, stop, and resume assessments within the specified completion window. This flexibility accommodates the fatigue and illness many oncology patients experience, ensuring more complete and accurate data collection.

4. System Integration. Integration with other study systems, such as IRT (Interactive Response Technology), can streamline site workflows and improve overall study efficiency. For example, using IRT to trigger eCOA assessments could reduce the need for multiple logins and ensure proper sequencing of study activities.

5. Reporting and analytics. Robust reporting on questionnaire compliance and preliminary results helps sponsors monitor study progress and patient well-being.

6. Translation needs. Many oncology trials are global. Ensuring eCOA providers can deliver properly translated and linguistically validated questionnaires in all required languages is key to data consistency.

Common eCOA Assessments in Oncology

When sponsors are unsure about which COA instruments to use or how frequently to administer them, it is beneficial to engage COA scientists early in the strategy development process to ensure that the selected measures truly capture the intended outcomes and meet regulatory standards. These experts can provide invaluable guidance in selecting the most appropriate instruments that align with study objectives and are sensitive to the expected treatment effects. They can also help determine the optimal assessment frequency, balancing the need for comprehensive data with considerations of patient burden and data quality. COA scientists are well-versed in regulatory expectations and can provide strategic advice on endpoint strategies, increasing the likelihood of acceptance by regulatory bodies. Some of the most frequently used COA instruments in oncology trials include:

• EORTC QLQ-C30: A core quality of life questionnaire for cancer patients, with additional cancer-specific modules
• PRO-CTCAE: Patient-reported outcomes version of the Common Terminology Criteria for Adverse Events
• FACT scales: Functional Assessment of Cancer Therapy measures
• EQ-5D: A standardized measure of health status
• PROMIS measures: Patient-Reported Outcomes Measurement Information System scales
• PGI-C/PGI-S: Patient Global Impression of Change/Severity
• CGI-C/CGI-S: Clinician Global Impression of Change/Severity
• Custom dosing diaries

Many of these validated questionnaires are available in eCOA libraries, allowing for rapid implementation. Working with an experienced eCOA provider can help expedite questionnaire licensing and ensure that the scientific COA strategy is appropriately mapped to aproper electronic implementation. Many eCOA vendors partner with Patient-Centered Outcomes specialists who can provide this scientific input alongside the technical eCOA implementation.

One assessment gaining traction in oncology trials is the PRO-CTCAE (Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events). Developed by the National Cancer Institute, this tool focuses on capturing symptomatic dosing toxicities specific to cancer. Its use is becoming more prevalent in both early and late-phase studies as regulators increase scrutiny on sponsors' ability to effectively monitor dosing toxicities.

eCOA Data Considerations in Oncology

In oncology trials, eCOA data plays a unique role that requires careful consideration. While it typically supports secondary or exploratory endpoints rather than serving as the primary outcome measure, its importance in capturing the patient experience should not be underestimated. Unlike other therapeutic areas, COA data in oncology is rarely used as part of inclusion or exclusion criteria, focusing instead on tracking changes throughout treatment. The emphasis is often placed on measuring change from baseline rather than absolute scores, as this can provide more meaningful insights into treatment effects and disease progression.

A critical aspect of eCOA data analysis in oncology is the careful handling of missing data, particularly when it results from disease progression or treatment-related complications. This requires a well-thought-out statistical analysis plan that accounts for the potentially non-random nature of missing data. Additionally, in cases where caregiver-reported outcomes are collected alongside patient-reported data, it is crucial to clearly differentiate between these sources to maintain data integrity and allow for appropriate interpretation.

By keeping these considerations in mind, researchers can maximize the value of eCOA data in oncology trials, providing a more comprehensive understanding of treatment impacts on patients' lives.

Site User Experience Considerations for eCOA Implementation

Site staff play a crucial role in the successful implementation and execution of eCOAs in clinical trials. Their experience with the eCOA platform can significantly impact data quality, patient compliance, and overall trial efficiency. To optimize the site user experience, several key factors should be considered.

First and foremost, comprehensive training is essential. Site staff should receive thorough instruction on the eCOA system's functionality, protocol-specific requirements, and best practices for patient interaction. This training should cover the system's technical aspects and strategies for encouraging patient engagement and troubleshooting common issues. Additionally, providing an intuitive site portal is vital. This portal should offer streamlined tools for managing patient profiles, monitoring compliance in real-time,accessing preliminary data and provide a means to swiftly identify trends and data anomalies that may pose risks to study endpoints. The ability to quickly identify and address any data issues can enhance the site's ability to maintain high-quality data collection.

Furthermore, integration capabilities with existing site systems can significantly improve workflow efficiency. By allowing the eCOA platform to communicate with electronic health records (EHR) or clinical trial management systems (CTMS), redundant data entry can be minimized, reducing the workload on site staff. Lastly, robust technical support is critical. Offering on-demand assistance for any technical issues ensures that site staff can quickly resolve problems, minimizing disruptions to data collection and maintaining staff confidence in the eCOA system. By addressing these considerations, sponsors and eCOA providers can create a more positive and efficient experience for site users, contributing to the success of the clinical trial.

Regulatory Considerations

Regulatory bodies have placed increasing emphasis on patient-reported outcomes (PROs) in oncology trials, recognizing their value in capturing the patient experience and providing a more comprehensive assessment of treatment efficacy. This heightened focus necessitates careful attention to several key regulatory considerations throughout the eCOA implementation process.

When migrating paper questionnaires to electronic formats, it is crucial to adhere to best practices that ensure the integrity and equivalence of the measures. This includes maintaining the original questionnaire's layout, response options, and instructions as closely as possible in the electronic version. Proper copyright permissions and licensing must be secured for all instruments used, demonstrating respect for intellectual property and ensuring legal compliance.

Robust audit trails and data integrity measures are essential components of any eCOA system, providing transparency and traceability that regulators expect to see. For instruments transitioning from paper to electronic formats, evidence of measurement equivalence is often required. This typically involves conducting small-scale studies to demonstrate that the electronic version produces comparable results to the original paper version, thus validating its use in clinical trials.

Finally, PRO-based endpoints must be clearly defined in the statistical analysis plan, including specifications for handling missing data and methods for interpreting clinically meaningful changes. By addressing these regulatory considerations proactively, sponsors can enhance the credibility of their eCOA data, facilitate smoother regulatory reviews, and strengthen the overall value of their oncology clinical trials.

Future Trends in Oncology eCOA

The landscape of eCOAs in oncology is rapidly evolving, driven by technological advancements and a growing recognition of the importance of patient-reported data. In the coming years, we can anticipate a significant shift towards greater utilization of PRO data to support labeling claims, as regulatory bodies increasingly value patient perspectives in evaluating treatment efficacy and safety.

The integration of PRO-CTCAE is likely to expand into early phase trials, providing valuable insights into treatment tolerability from the patient's perspective at earlier stages of drug development. The trend towards remote and decentralized trials is expected to accelerate the adoption of BYOD approaches and remote PRO capture, offering greater flexibility and potentially improving patient compliance. As wearable devices and sensors become more sophisticated, their integration with eCOA systems will provide a more comprehensive picture of patient health, combining subjective patient-reported data with objective physiological measurements. To address concerns about patient burden, especially in the context of complex oncology trials, computer adaptive testing is likely to see increased implementation, tailoring questionnaire length and content based on individual patient responses.

Finally, the real-time nature of ePRO data collection opens possibilities for implementing alert systems for adverse event monitoring, potentially improving patient safety and allowing for more timely interventions. These trends collectively point towards a future where eCOA in oncology becomes more patient-centric, technologically advanced, and deeply integrated into the overall clinical trial process, leading to more comprehensive and meaningful assessments of cancer treatments.

CHECK LIST: Optimizing the Patient Experience

• Keep questionnaires concise and only include the most relevant measures
• Use skip logic to minimize irrelevant questions
• Allow flexible completion windows when possible
• Provide clear instructions and an intuitive user interface
• Offer multiple language options
• Enable caregiver assistance when appropriate
• Consider larger font sizes and high contrast color schemes for visually impaired patients