Subject-Reported Diary Data: What’s the problem with paper?

Subject compliance in any clinical trial is always a concern, and may be a catalyst to use electronic diaries, or some modality other than paper.  This blog entry will discuss a few examples of when subject compliance is critical, data that exposes risks associated with paper, and what the FDA guidance suggests about unsupervised subject-reported data.

Below are a few examples of when subject compliance plays a crucial role in the overall success of a study.

  • Subject-Reported Diary data used to determine randomization eligibility.
    • Example:  Subject must be 80% compliant with placebo dosing during run-in period to be eligible for randomization.
  • Subject-Reported Diary data used to determine dosing escalation during study.
    • Example:  Subject’s daily symptoms are used to calculate dosing escalation throughout treatment period.
  • Subject-reported Diary data used to determine if subject withdrawn from study.
    • Example: Subject’s compliance with daily survey (90% compliance) is required for data to be considered in study results.

The examples above are taken from studies in which the Sponsor used electronic diaries to mitigate the risks associated with paper.

So what’s the problem with using paper to capture these critical data points? 

A study published in Volume 324 (18 May 2002) of the BMJ explains the risk introduced when using paper diaries to capture important data from subjects at home.  In their study, half the subjects were given paper diaries, while the other half were given electronic diaries.  What the paper-diary subjects did not know is their diaries came equipped with a photo-sensor on the inside cover.   Although 90% of the subjects reported completing their paper diary according to the protocol specified time periods, the embedded photo-sensor confirmed only 11% of the subjects actually completed the diary as instructed.  Instead, most often the subjects opened their diary in the parking lot either immediately after it was dispensed or just prior to their follow-up clinic visit.  The same study discovered over 94% of subjects were compliant when using their electronic diary.   You can read the BMJ article in its entirety by clicking here.

When discussing this study with Sponsors, their first question is typically – What does the FDA say?  An excerpt from FDA Guidance on Patient Reported Outcome Measures (December 2009) states the following:

“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.”

It’s reasonable to deduce from this guidance, that the most effective way to satisfy this requirement is to use an electronic diary that keeps a real-time audit trail with a time and date stamp for each subject-reported entry.

You can read the FDA PRO Guidance document by clicking here.

Return to next week to read about techniques used in clinical trials to improve compliance.


Webinar: eSource in Clinical Trials, Pros/Cons & Lessons Learned from Phase III Clinical Trials

For those of you who missed the eSource Webinar hosted by assisTek on April 4, 2013, you can still watch the entire Webinar on video below!


This webinar will focus on Real-Life examples of ongoing Phase III global clinical trials using mobile Direct Clinical Data Capture (eSource) solutions. Topics discussed will include:
- Overcoming data quality and data access problems that plague studies using the traditional paper transcribed to EDC process.
- Supporting site workflow with eSource
- Cost Savings Model (Query Reduction & Elimination of SDV)
- Impact and Integration with external clinical databases (EDC, etc)

 Please contact Evonne Roberts, with any questions or to schedule an on-site demonstration.


eSolutions to Meet FDA Requirements to Maintain Adequate Records (Part 6 of 6)

This post is the final of a 6 part series. Visit weekly or enter your email to subscribe.

FDA “… recommends that clinical data be entered electronically by study site personnel at the time of the subject visit to avoid transcription from unnecessary paper records1. The acronym “ALCOA” is frequently used in reference to best practices related to source documentation. When eSource solutions are selected and developed appropriately, data is attributable to a unique user with a secure password and role-specific privileges; legible in a clean and easy to read standardized format; and contemporaneous with a date and time stamp for every entry/edit/modification. Original records initially captured electronically can include direct entry of clinical data into a study database, data transmitted from an electronic health record, and electronic diary data entered by a subject or transmitted from an automated instrument that captures a biological result. eSource provides the opportunity to engineer accurate data with boundary and edit checks for missing and/or out of range data devoid of contradicting information often represented by subjective reporting in an unstructured format.

To minimize risks related to FDA requirements to keep accurate records and protect human subjects, sponsors using electronic source solutions should keep records of:

  • system validation and maintenance,
  • system specifications showing customization to fit the eSource for the purpose of the study,
  • 21 CFR § 11 compliance and
  • data integrity practices.

Ultimately, the same system development collaboration and documentation intended to manage risk, will have the added benefits of quality design, validated performance and accurate data capture with electronic efficiencies that reduce data noise, facilitate analysis and expedite time to data lock…and that’s what is best for patients.

eSource Best Practices
1Guidance for Industry Electronic Source Documentation in Clinical Investigations Draft Guidance. U. S. Department of Health and Human Services, Food and Drug Administration, Office of the Commissioner. December 2010. Retrieved October 23, 2012 at…/Guidances/UCM239052.pdf


eSolutions to Meet FDA Requirements to Maintain Adequate Records (Part 5 of 6)

This post is Part 5 of a 6 part series. Visit weekly or enter your email to subscribe.

FDA guidance suggests sponsors should include information about the intended use of computerized systems in their data management plan. Compliant with 21 CFR part 11, this data management plan should also describe the “security measures employed to protect the data and a description of the flow of electronic data”1. In the workflow demonstrated in the Figure below, note that a unique user name and password is required to access the system. Each user is associated with a user group and each user group is limited to specific roles/functions within the eSource. The user activity is date and time stamped in real time and an audit trail serves as the automated documentation of who did what, to whom and when.

Figure 3 

eSource systems/vendors should:

  • support controlled and secure access typically by
    • a username/ ID and password,
    • user roles,
    • role-specific privileges,
    • data encryption, and
    • workflow
  • create and maintain an audit trail of data entry and data revisions including
    • the “old” value,
    • the “new” value,
    • date and time stamp,
    • and the user who entered/changed the data
    • reason for the data edit
  • have a provision for data transfer and storage for the time required by the regulations

to be continued…

1 Guidance for Industry Electronic Source Documentation in Clinical Investigations Draft Guidance. U. S. Department of Health and Human Services, Food and Drug Administration, Office of the Commissioner. November 2012. Retrieved December 18, 2012 at






Electronic Adverse Event Reporting and Follow-up

Patient safety has never been more important than it is today in Clinical Trials.

assisTek has built an infrastructure to support the collection of patient and clinician reported adverse events, all electronically.  Emphasis has been placed on what matters most – accurate and timely reporting of symptoms, proper notification to the study team and immediate access to data.

Two relevant examples of how symptoms are captured, team members are notified, and data is updated are below:

Patient eDiary Example:  Patient reports potential Adverse Events from home, Study Team is instantly notified and has access to data for follow-up & updates.

Direct Clinical Data Capture Example:  Clinician collects Adverse Events from patient, Investigator is instantly notified and has access to data for follow-up & updates.

Contact assisTek to understand how your study can benefit. (and yes, we will reply!)

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