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  • Subject-reported Diary data used to determine if subject withdrawn from study.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 www.assistek.com/whats_new/ next week to read about techniques used in clinical trials to improve compliance.

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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 http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM328691.pdf

 

 

 

 

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Paper Diaries – Risky Business

 

Many in our industry refer to the “parking lot syndrome” when describing patients rushing to complete days’ worth of their paper diaries for their clinical trial just before their site visit.

Did you know that this “syndrome” was actually captured in a study published by the British Medical Journal (BMJ2002;324:0.6)?

It found that although 90% of subjects reported completing the paper diary on time, only 11% actually completed it as instructed.  They were able to track paper diary entries by embedding photo sensors into the diary binder (to determine when the binder was actually opened).   This compares to a 94% compliance rate with an electronic diary.

The complete article can be read here.

Equally as interesting, the FDA PRO guidance(published in 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.” (pg. 14)

This guidance indicates the regulatory authorities are keenly aware of the non-compliance associated with paper diaries, and intend to monitor patient compliance with diary entries according to protocol requirements.

If your study is designed to collect patient reported outcomes, study endpoints, symptoms, or undesirable events from patients at home, consider using an electronic diary with an automatic date and time stamp, to facilitate regulatory compliance.

You can learn more about assisTek’s Patient eDiaries by clicking here, and see pictures here.

 

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