How eCOA Improves Data Quality in Clinical Trials

Important aspects of COA data quality

COA data are often used to derive primary and key secondary endpoints in clinical trials. But even when their data represent exploratory endpoints, inferences made using them provide supporting evidence valuable in regulatory new drug applications. For this reason, ensuring reliable inference making through high quality COA data is imperative.

It is helpful to consider aspects of data quality to drive reliable inference making in a number of ways: (1) Are the data collected free from ambiguous, conflicting or erroneous entries, (2) Do the data have accuracy and integrity, for example were they completed in a sufficiently timely manner to ensure accurate recall, and (3) Is there sufficient data to make reliable inferences (i.e., is the amount of missing data low enough)?

These principles apply for all the categories of COAs we collect – such as patient-reported outcomes (PROs), observer-reported outcomes (ObsROs), clinician-reported outcomes (ClinROs), and Performance outcomes (PerfOs). (See blog to read more about COAs). However, in the case of PROs and ObsROs we rarely have the ability to query data entered by a patient or observer in the same way that we can for clinician-entered values, and so driving high data quality from the start is of vital importance. This is where electronic capture of COA data, eCOA, plays a vital role in driving data quality and integrity, and reducing missing data.

How eCOA drives data quality

COA measures, such as patient-reported outcomes, collected on paper are prone to data quality issues. This applies to paper data collected in supervised conditions, such as site-based questionnaires, and in unsupervised conditions, such as symptom diaries completed at home.

Home diaries collected using paper are associated with data quality issues including:

1. Missing values – patients completing PROs at home may chose to skip questions or miss data fields accidentally when completing these on paper.
2. Ambiguous or erroneous data – patients may complete a questionnaire item in an ambiguous manner – perhaps selecting options by ticking two checkboxes, or making it difficult to determine their response when making a correction to their initial entry. Or, they may enter responses that are out of range.
3. Conflicting data – where responses to subsequent questions depend on a specific response, this may lead to conflicting entries when collecting on paper. For example, a patient may indicate to a first question ("Did you wake up during the  night?") that they did not wake up in the night, and then subsequently record 3 awakenings ("How many times did you wake up in the night?").
4. Extraneous data – patients can write other “helpful” notes on their paper diaries, such as identifying an adverse event. This can create challenges for data managers and monitors in how to handle this additional data.

When these data are completed by the patient, it is typically impossible to go back to the patient at a later date to query their entries where data quality concerns are observed.

Electronic solutions, such as ePRO apps, mitigate these issues. Missing values can be prevented, where appropriate, by preventing question skipping ensuring that all questions in a measure are answered, leading to full data for scoring. Electronic solutions are typically configured to allow only a single response to a specific question, avoiding issues with response ambiguity. Range checks can prevent out of range entries. ePRO solutions prevent conflicting data by, for example, including branching logic, for example, to avoid asking redundant questions based on previous responses. And finally, electronic solutions prevent additional extraneous data collection.

We see the above data quality issues also reflected in questionnaire data collected at site.

Read more about the benefits of ePRO compared to paper in our white paper. 

How eCOA drives data accuracy and integrity

COA measures are typically associated with a recall period. Some measures ask about patient status at the current point in time (e.g., How bad is your pain right now?), and others over a defined time interval (e.g., How bad was your pain at its worst today?). Accurate assessment can only be assured when patients can accurately recall their health status associated with the time period in question. Where this is not possible, entries are affected by recall bias.

The 2009 FDA guidance on patient-reported outcomes expresses the importance of ensuring the timeliness of patient diary entries on data integrity and states “If a patient diary or some other form of unsupervised data entry is used, we plan to review the clinical trial protocol to determine what steps are taken to ensure that patients make entries according to the clinical trial design and not, for example, just before a clinic visit when their reports will be collected, or at other times – such as just prior to a clinic appointment.”

Using a paper diary completed by patients at home, it’s impossible to ensure that entries are completed at the times required, and not backfilled in the parking lot ahead of a clinic appointment. This potential undermines the integrity of the data, and may lead to reduced accuracy.

ePRO solutions are able to apply “completion windows” to ensure that entries can only be made within a specified period of time. Time and date stamped entries provide a measure of completion timeliness, and evidence to support the integrity of the data, addressing the concern cited by FDA in their guidance (above).

Another property of eCOA solutions is the ability to ensure that all measures are completed in a defined order. This cannot be assured using paper questionnaires. In some cases, there is evidence that the order of questionnaires can influence patient responses, as the context of previous questions and answers can contribute to the patient perspective.

Read more about the benefits of ePRO compared to paper in our white paper.

How eCOA reduces missing data

Missing values can undermine the ability to make reliable inferences from the clinical data we collect in clinical trials. This applies to all the data we collect, not just COA data.

As described above, COA data collected on paper can be associated with missing entries – either accidentally or deliberately skipped. And, paper source records can be lost at site or at home before data can be transcribed into the EDC or data management system.

eCOA systems can be configured to prevent question skipping, where appropriate, so that completed measures are composed of a complete set of responses to aid accurate scoring.

Further, ePRO solutions can be configured with audible alarms and notifications to remind the patient when an entry is due, and drive regular on-time completion. These systems often have other completion compliance monitoring features to drive complete datasets. These may include escalation notifications to site when specific patients’ completion rates fall below a defined threshold; and real-time reports for sites, CRAs and sponsors to monitor completion rates throughout the study. Timely follow up by sites can drive good completion rates for individual patients.

Read more about the benefits of ePRO compared to paper in our white paper.

Overall, as you’ll read above and in our white paper, eCOA platforms, including ePRO solutions, are able to drive and demonstrate high data quality, data integrity, and drive reduced missing data.

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