Efficacy assessments play a vital role in clinical trials, providing essential data on treatment success. This discussion focuses on 3 main aspects: capturing clinical outcome assessments (COAs), comparing paper versus electronic data capture (eDC), and ensuring compliance with patient-reported outcomes (PROs) for at-home subjects questionnaires. Examining these elements provides a comprehensive understanding of current practices and considerations in efficacy assessments, emphasizing the importance of accurate data capture and compliance in clinical research.
The Role and Capture of COAs: A Comprehensive Overview
The COA essentially determines the success of a clinical trial. It typically involves questionnaires or scoring, conducted by either the principal investigator (PI) or the patient. Most primary endpoints are based on the PIâs evaluation, but in some indications, such as in chronic spontaneous urticaria, the primary endpoint is assessed by the patient.
Clinical reported outcomes (ClinROs) are assessments conducted by PIs, they often serve as the primary endpoint. As the great majority of ClinROs in dermatology are based on the evaluation of visual severity symptoms, they have a strong subjective component. Therefore, it is crucial to control the training of the PI and manage the variability in their ratings. Additionally, the tools used to capture this data are of utmost importance. Consequently, significant emphasis is placed on how investigators at the site will capture this information.
On the other hand, PROs are assessments completed by the subjects themselves. Regulatory authorities increasingly require a correlation between the patientâs experience of their disease and the studyâs outcomes. Therefore, it is essential to capture this data directly from the patients. These assessments can range from a simple numerical rating scale (e.g., 1 to 10, âHow do you feel?â) to composite scores from multiple questions, or more complex quality of life questionnaires with up to 15 questions. There are various methods to capture these outcomes, and the approach depends on the specific requirements of the study.
Key Considerations from Paper vs. EDC
This is a common discussion with sponsors. Although one might expect that by 2025 everything would be completed and captured electronically, this is not always the case. Regarding PROs, the schedule of events of a protocol may include daily questionnaires or scoring by the subject performed at home. When this occurs, collecting electronically avoids the need for several days of data collection on paper diary, which would then have to be entered into the EDC and monitored by the CRAâa cumbersome process. Therefore, when these assessments are to be completed at home, they should typically be captured electronically.
When a subject attends a site visit and completes a questionnaire in front of the PI, it does not necessarily need to be electronic, since the site will already have their source documents on paper. Very few sites currently build a fully electronic set of source documents for all data points captured. As they will generate the paper source documents, they will incorporate the licensed and translated paper PRO version provided.
Some sponsors prefer to have all data capture performed electronically, which is definitely possible. However, this approach requires significant preparation and upfront costs. Setting up electronic PROs can sometimes take longer than the usual study startup and become the rate-limiting step, potentially delaying it. To shorten timelines, these factors can be adjusted. Using paper for everything allows the study to start sooner.
There is a trade-off depending on the number of questionnaires and the licensing requirements. Most questionnaires are copyrighted, and obtaining the necessary licenses sometimes involves various approval processes and timelines. This is a key factor in deciding whether to use electronic or paper PROs.
In Indero trials, paper versions are typically used for ClinROs conducted by physicians. The CRO has a thorough and stringent process for providing source documents to the sites, leveraging their extensive experience. Additionally, Inderoâs CRU brings expertise in creating effective paper versions of ClinROs. This internal expertise allows the CRO to supply worksheets to the sites, thereby better controlling how data is captured.
There is a balance on the cost efficiency of the electronic system compared to data entry in EDC and monitoring of the data field. For efficient data entry, EDC can be used to save time and costs associated with building and managing data. It ensures that the case report form (CRF) for electronic data entry is structured exactly like the paper version, with the same field order and cumulative scoring. Stringent controls are applied to these processes to ensure efficiency, accuracy, and precision, similar to the paper-based approach.
Some sponsors prefer to capture assessments electronically, providing electronic tablets to both the PI and the subjects. While sites can generally make this work through close relationships and discussions, challenges arise when electronic tablets have low batteries or connectivity issues. If a subject is present and the COA cannot be entered, it creates significant pressure on the sites. Technical issues can complicate this process, which is why many clinical sites still find paper to be more reliable than electronic. Clinical sites often indicate that this is often a factor that can trigger enthusiasm for enrolling more on a specific study with paper COA vs. another with a challenging electronic system. As mitigation strategy, paper is often kept as a backup. When studies are conducted electronically, it is essential to address any technical issues that may arise.
Effective Management of PRO Compliance for At-Home Subjects
When subjects capture data at home, it is preferred to do it electronically, primarily for compliance reasons. If given a piece of paper to record their scores over the next several days, patients often miss the last few days and end up filling it out in the parking lot before their clinic visit. This âparking lot syndromeâ raises concerns about the accuracy of the data. Did the subject truly remember how much they were itching 4 days ago? These questionnaires are very precise, often asking about symptoms in the last 24 hours.
Providing data capture electronically ensures a well-structured and more accurate collection process. The electronic device can be programmed to allow data entry within specific windows, such as a 24-hour period, after which the entry is no longer permitted. These boundaries can be customized based on the questionnaire and sponsor requirements. Additionally, the system sends reminders if the patient misses a scheduled entry time, which helps improve compliance. This way, electronic capture is more effective, even if the subject occasionally misses an entry.
Typically, electronic PRO providers have a standard compliance rate of 70%, while most sponsors want 100% compliance. Indero sets a higher standard with an 80% compliance rate, and the CRO has been quite successful in achieving this rate. Numerous measures were implemented to reach this goal.
One crucial aspect is training. Clinical Research Associates (CRAs) ensure sites train subjects properly, emphasizing that while missing 1 day is understandable, they must not miss more than a specific number of days to maintain the 80% compliance rate. This target is communicated clearly to everyone involved: the subjects, the sites, the CRAs, data manager, CTM, etc.
Compliance for each subject is tracked closely, with reports generated at different levels. CRAs review subject compliance before their visits, and data management flags any compliance issues during data cleaning. While PROs cannot be queried since they come directly from the subjects and the data cannot be changed, compliance can still be monitored.
One of the key risk indicators in such a study is PRO-compliance. When a low compliance is flagged, actions for the project teams are triggered such as conversation with the site and retraining, allowing the site to follow up with the subject. Although some sites find this stringent, it ensures that everyone focuses on the data. This should be integrated into the plans and processes to help achieve compliance. Additionally, tools such as reminders for the subjects are crucial.
Key risk indicators and central monitoring help identify whether a site or a specific subject is problematic, allowing for appropriate actions to be taken. This approach effectively manages compliance for PROs captured electronically at home.
To conclude, optimizing efficacy assessments in clinical trials involves careful consideration of how COAs are captured, the choice between paper and EDC, and ensuring compliance with PROs for at-home subjects. Accurate data capture and high compliance rates are essential for reliable trial results.
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About the AuthorÂ
France Wagner, M.Sc.
France Wagner is the Senior Director of Operational Strategy at Indero. With over 15 years of experience in the CRO industry, France has expertly managed projects from phase I to III. Her extensive background includes overseeing dermatology trials for conditions such as atopic dermatitis, psoriasis, itch, alopecia areata, and hidradenitis suppurativa, utilizing both topical and systemic solutions. Franceâs expertise and strategic vision have been instrumental in advancing Inderoâs mission of improving patient outcomes in dermatology.
