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- Subject-reported Diary data used to determine if subject withdrawn from study.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.