When site personnel complete subjects’ e-diaries, bad things happen. Don’t let them happen to your company!
This FDA Warning Letter questions the validity and integrity of ePRO data captured at a clinical investigator site. What’s a sponsor to do to avoid the same fate?
Learn from your peers (and competition).
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#1 problem according to the FDA.
1. Select an ePRO provider who can support the Primary Investigator’s access to source data.
To help you choose a provider, ask:
- What happens to your subjects’ diary data?
- Does it disappear from the device, evaporating into the cloud hosted by your ePRO provider?
- Is your provider’s solution to print “copies” of the device data at the site and instruct site personnel, monitors, and auditors to rely on paper for their oversight activities?
If so, you may have a problem. Unless you and the provider have worked together to confirm the printout is an accurate and complete representation of the electronic record and is equivalent in content and meaning, you are relying on the wrong source. The PI, monitors, and auditors need access to the source and should be reviewing audit trails as part of their oversight activities.
2. Write protocols and supporting documents carefully.
In most cases, the subjects are supposed to complete the diaries themselves.
That said, there are times when subjects may be unable to complete the diaries themselves. As in the case with Dr. Frazer’s site, “the patient was either unwilling to complete the pain score or too disoriented to write into the diary or use the LogPad.”
What is a natural reaction of site personnel when this happens?
Site personnel normally want all possible data to be collected so that the site and study will be successful. With all good intent, when subjects are unwilling or unable to complete the ePRO, site personnel may offer to do it on behalf of the subject.
Be sure the protocol, site user manuals, and instructions to subjects provide clear instructions. Most ePRO devices only allow for 1 user. When site personnel use the subject’s user id and PIN to access the device and enter data, the data are not attributable to site personnel – they are attributable to the subject.
This could be viewed as falsifying data!
So, when subjects must complete ePRO diaries on their own, be sure to allow for the possibility of missing data and…
3. Train, train, train…
The following groups need training to protect the integrity of your company’s ePRO data:
All site personnel need to understand who should and should not enter ePRO data. If you do not want site personnel entering ePRO data on behalf of a subject, you must train them on what to do when the subject cannot or will not enter data.
A well-written 483 response can mitigate further action, including Warning Letters.
Train site personnel (especially the Primary Investigator) on how to host a regulatory inspection and how to respond to 483 findings. In the example below, the response was provided on the last day of the inspection. You have 15 business days to respond to a 483 and to have the agency take your response into consideration as they think about next steps.
Clinical Trial Subjects
Feelings of altruism often motivate clinical trial subjects. When subjects understand why it is important for them to enter their own data, you increase the chances of compliance.
The ePRO dispensing process should always include a discussion of roles and responsibilities for ePRO diary use.
Monitors and Auditors
ePRO data are typically not queried in the same way traditional CRF data are queried: what the subject entered is what they entered, full stop. However, monitors and auditors should be trained on how to look at the data to establish confidence that the data are attributable to the subject and have been entered at the protocol-required times.
Learn more about how FDAzilla can help you achieve your quality and inspection preparation goals: get 483s, Inspector Profiles, Enforcement Analytics, and GMP Regulatory Intelligence. Contact us if you ever have questions at email@example.com.
About the Author
Jamie Colgin is Govzilla’s GCP Product Manager and is the recipient of the prestigious Charles H. Butler Excellence in Teaching Award. She joins Govzilla from Colgin Consulting, Inc.