Electronic ePROs vs. Paper PROs for Clinical Trials: A Comparison

There are few real controls in the administration of paper questionnaires for clinical trials, so there are data quality and protocol compliance risks at all sites at all times.

Many clinical study teams are inclined to collect PRO data from patients using paper questionnaires because that's the way it's historically been done, and there is a perception that paper is less expensive. However, research shows that paper PROs are highly deficient and that there is often not a large cost difference between paper and electronic PROs.

The table below shows issues that are important in PRO data collection, and then indicates whether electronic PROs or paper PROs can address each issue.

ePRO

Paper Questionnaires

Higher Data Quality/Fewer Queries ePRO systems have extensive edits to ensure high data quality, as well many other controls to ensure data is absolutely complete and correct. There are few real controls in the administration of paper questionnaires for clinical trials, so there are data quality and protocol compliance risks at all sites at all times. As a consequence, using paper questionnaires to collect patient reported outcomes data results in hundreds or thousands of queries. High query volume not only suggests high data quality risk, but also introduces significant cost and time issues. By contrast, properly validated electronic systems produce very high quality data, very low query volume, and insignificant cost and time to resolve queries. As an example, on assisTek's last global clinical trial, there was only one query on the data file. Compared to a paper-based PRO, this is enormous improvement on all quality metrics.

High Compliance Studies show conclusively that patients are not compliant with paper-based PRO data collection at home. As an example, a well known study published in the British Medical Journal showed that patients reported 90% compliance with their paper diaries, but electronic sensors in their paper diaries indicated the patient compliance was only 11%. At the same time, patients who had electronic diaries had an actual compliance of 94%.

Patient Preference Studies also indicate that patients and clinic staff prefer electronic PROs over those on paper. A study published in the Drug Information Journal on assisTek systems showed that 88% of patients and 91% of clinic staff prefer ePRO or have no preference.

Cost Study teams often assume that ePRO is more expensive than paper PROs. This is not correct! An analysis of the 10 Most recent trials for one of assisTek's customers showed that 8 of the 10 studies were less expensive than paper, providing a total savings of $1.6 M.

Patient Engagement to Encourage Compliance Because electronic systems are interactive, welcome screens and daily diary screens can be designed with graphics and summaries to engage patients, give them feedback, and involve them in their own compliance. Although it's not known whether studies have been done on this topic, most study teams understand that real feedback is likely to engage patients and increase compliance over a static medium.

Accurate and Complete Data Throughout the Trial Enables True Study Management Using assisTek's new technologies, smart phones and netbooks, data is sent automatically from each patient's device through the local cell phone network. Websites enable real study management because the study team has real time access to 100% complete and accurate study reports at all times.

Instant Compliance and Safety Monitoring - Because data is transferred automatically without patient invervention, the study team can truly monitor patient compliance and quickly take corrective action when needed. In addition, if the patients indicates a safety issue (e.g., being in extreme pain) emails, text messages, or phone calls can be sent electronically to designated study team members to take appropriate action.

Better Use of Study Team Time Study teams often don't realize the quantity of paper that needs to be managed to enable high quality PRO data. Paper-based ePRO in a clinical trial can often result in over 100,000 pieces of paper. Most professionals agree that it is not possible to manage this amount of paper within a study team, nor is it a good use of their skills and experience.

Security, Attributability, Evidence of Compliance With paper questionnaires it is impossible to know who really completed them. Electronic systems require usernames, passwords, or PINs to help ensure that only the enrolled patients complete the questionnaires. In addition, electronic systems provide date and time stamps on every questionnaire record so that there is clear evidence of patient compliance.

Summary Although PROs on paper may appear "safe", the table above shows their many failings. Study teams need to consider these shortcomings carefully before choosing an ePRO data collection methodology for their clinical studies.