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We have the pleasure of speaking with France Wagner, Senior Director of Operational Strategy at Innovaderm. With over 15 years of experience in the CRO industry, France has expertly managed projects from phase I-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.
We will explore efficacy assessments into 3 main points:
- Data capture of clinical outcome assessments (COAs)
- Paper vs electronic
- Patient reported outcomes (PROs) compliance for at-home subjects
The Role and Capture of COAs: A Comprehensive Overview
The clinical outcome assessment 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 PI’s evaluation, but in some cases, such as 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. 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 patient’s experience of their disease and the study’s 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, ‘How do you feel?’) 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. Electronic Data Capture
This is a common discussion with sponsors. Although one might expect that by 2024 everything would be done and captured electronically, this is not always the case. Regarding PROs, the schedule of events for a protocol may include daily questionnaires or scoring by the subject at home. When this occurs, it avoids the need for 72 days of data collection on paper, which would then have to be entered into the EDC and monitored – a cumbersome process. Therefore, when these assessments are done at home, they should typically be captured electronically.
When a subject attends a site visit and completes a questionnaire in front of an investigator, it does not necessarily need to be electronic. This is because the site will already have their source documents on paper. Unfortunately, few sites currently have electronic data capture for everything, so they will have the paper ready for capturing PROs as well.
Some sponsors prefer to have everything done 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, 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 questionnaire and the licensing requirements. Each questionnaire is copyrighted, and obtaining the necessary licenses involves various approval processes and timelines. This is a key factor in deciding whether to use electronic or paper PROs.
In Innovaderm 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, Innovaderm’s 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 captures.
Using electronic data capture saves time and costs associated with building and managing data. It ensures tat the 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 conduct assessments electronically, providing tablets to both the PI and the subjects. While sites can generally make this work through close relationships and discussions, challenges arise when 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 reliable. 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 14 days, patients often miss the last few days and end up filling it out in the parking lot before their clinic visit. This ‘parking lot syndrome’ 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 closed. These boundaries can be customized based on the questionnaire and sponsor requirements. Additionally, the system send 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. Innovaderm 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. 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, and data management.
One of the key risk indicators in this study is lower compliance. When this occurs, it flags every training and conversation with the sire, 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 – sent after 1 hour and then after 2 hours – are crucial.
Compliance for each subject is closely tracked, 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.
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.
As we conclude another illuminating episode of Phase Forward, we find ourselves at the crossroads of science and progress. Remember that behind the jargon and statistics, lies stories of unwavering commitment, meticulous observation, and the pursuit of evidence that shapes our understanding of health and disease. Stay at the forefront of knowledge and innovation and follow Phase Forward on your preferred platform. My name is Valerie Coveney. Thank you for joining us. Until next time.
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