eCOA vs. paper

Which should I use for my upcoming trial?

Valdo Arnera, M.D. – eCOA Scientific Advisor

We recently discussed the basics of eCOA and how it improves clinical trial data quality. For example, when compared to paper-based assessments, eCOA eliminates inconsistent data, increases patient compliance, is preferred by patients and recommended by regulatory agencies.^1-4

In most cases, it is recommended to use eCOA; however, there are scenarios when paper may be considered. In this piece, we discuss occasions where the use of eCOA for capturing patient data is critical versus when it is recommended and how sponsors can reap the many benefits electronic data capture provides.

When is it critical to use eCOA?

“There are several scenarios when it is critical to capture your endpoint data electronically rather than on paper.”

Valdo Arnera, M.D. – eCOA Scientific Advisor

These scenarios include:

• Questionnaires and/or daily diaries which are supporting primary endpoints: eCOA should be used when the success of your trial resides on the collection of patient diaries, as electronic assessments deliver significantly higher-quality data and more accurate results than paper data collection.
• Questionnaires that don’t support primary endpoints but are unsupervised: Without the supervision of a healthcare professional, patients may procrastinate, inaccurately record, or forget to record entries in their questionnaire. Electronic assessments are designed to minimize or eliminate these problems through:
  • Alarms that are programmed to remind patients to complete their questionnaires appropriately
  • Software that prevents back and forward filling
  • Real-time reporting that automatically alerts sites when patient compliance is below a set threshold, allowing sites to intervene when necessary
• Monitoring for Suicidal Ideation and Behavior (SIB): Sites must know in real-time if a patient is experiencing suicidal thoughts. Electronic tools, such as the self-reported electronic Columbia Suicide Severity Rating Scale (eC-SSRS) or the interviewer-rated C-SSRS, can achieve this level of urgency. The patient-reported version of the C-SSRS provides increased patient honesty, reduces rater variability, and allows real-time suicide risk notification.
• Integrating data from another source: If patients inaccurately record or forget to record meter values from other devices like glucometers, eCOA features such as automatic data transfer and reminders offer an added layer of support.
• Complex ClinROs: Complex calculations and scoring are error-prone and can be eliminated with automatic calculations. An example here would be the Psoriasis Area Severity Index [PASI].
• Rare disease studies: These cases often have few participants in the study. It’s therefore essential to minimize missing and incomplete data.

When is it recommended to use eCOA?

To reduce burden and receive consistent, high-quality data, we also recommend using eCOA in the following scenarios:

• Oncology trials: Regulators recommend using eCOA in oncology trials⁵ and are now requesting additional information about drug efficacy beyond survival, such as quality of life (e.g., symptom relief).
• Large-scale studies: Errors incurred when using paper can result in significant delays and costs due to data cleansing and processing. This is especially true when working across diverse populations and in multiple countries.

In addition to these scenarios, there are several other key factors that underscore the advantages of eCOA. One of these is its ability to minimize data variability and enhance reliability. For example, a study by Merck Research Laboratories found that using electronic Patient-Reported Outcomes (ePRO) led to a 41% reduction in standard deviation compared to paper-based methods, resulting in more precise and higher-quality data. Read the full case study here.

When can paper be considered?

Aside from the scenarios mentioned above, there may be a small number of instances where sponsors could consider using paper. In the following three scenarios, paper may be an appropriate option.

• Studies with a very small patient population: The financial cost of incorporating eCOA may be greater than the burden of collecting data manually.
• Long-duration studies with infrequent questionnaire collection: the cost of deploying eCOA may make paper a more appropriate option.
• Phase 1 studies: For example, in a trial taking place on-site over a single day with a group of healthy volunteers, the likelihood of non-compliance using paper is low.

Prior to using paper in these scenarios, the risks outlined above should be carefully considered and we strongly recommend you speak to our scientific advisors.

Summary

It is important to understand when it is critical to use electronic Clinical Outcome Assessments and the immense benefits eCOA brings with it over paper-based data capture. Our Clario Science team is on hand to offer advice on which method is most appropriate for your trial. Contact our team of experts or visit our Science page for further information.

References

¹ Food and Drug Administration, FDA. 2009. Guidance for Industry: Patient-Reported Outcome Measures: Use in Medical Product Development to Support Labeling Claims.
² Food and Drug Administration, FDA. 2010. Guidance for Industry: Electronic Source Documentation in Clinical Investigations.
³ EMEA, 2005. Committee for Medicinal Products for Human Use. Reflection paper on the regulatory guidance for the use of health-related quality of life (HRQL) measures in the evaluation of medicinal products.
⁴ EMA 2014, Reflection Paper on the use of patient reported outcome 5 (PRO) measures in oncology studies
⁵ Food and Drug Administration, FDA. 2018. Clinical Trial Endpoints for the Approval of Cancer Drugs and Biologics, Guidance for Industry