Early versus postponed supplementary parenteral nutrition after major emergency abdominal surgery

Serious breach SB-68978

Sponsor became aware

2025-01-28

Date of breach

2024-04-18

Submission date

2025-01-31

Member states concerned

Denmark

Categories

Protocol

Areas impacted

Data reliability or robustness, Subject rights

Benefit-risk balance changed

No

Description

Sponsor has been made aware of a potential serious breach during a routine monitor visit by the GCP unit.

Subject rights:
An old version of the subject information sheet (deltagerinformation) has been kept in use at the site. The version used did not specify, that pseudo-anonymized data regarding their admission would be shared with two board-certified surgeons.
We deem this to be a serious breach on subject rights, as they might not have consented to the study had been given the full information.
The breach involves a total of 11 subjects. The pseudo-anonymized data for the 11 subjects has not been viewed or accessed by the two surgeons.
One subject was contacted twice as part of follow-up even though informed consent was withdrawn. This was not registered in the CRF at the time of follow-up.
Sponsor considers the above to be a serious breach of subject rights.

Data reliability or robustness:
The quality and robustness on data regarding "calorie intake registration" is inadequate. This data is needed to assess eligibility in the trial and to adjust the intervention. In several cases, calorie intake cannot be verified, as data cannot be converted to an actual amount of calories. For instance, this could be "25% of breakfast" but with no way to determine the contents of the breakfast and the amount of calories.
As a result, eligibility (intake < 50% of calorie requirement) cannot accurately be verified. This impacts the validity of data concerning inclusion and exclusion criteria, and subjects outside the scope of this trial may have been included.
Subject safety is not deemed to have been impacted. Although an exact calorie intake cannot be determined, clinical notes from patient charts indicate that intake is likely to have been below or around 50% of requirement. No serious adverse reactions occurred.
In some instances, IMP dose has deviated from the protocol because treatment was handled by the treating physician and a certified clinical dietician. These subjects will have been treated according to local guidelines and their safety has not been affected.
Overall, timely data registration in eCRF is lacking and must be improved.
Sponsor considers the above a serious breach on data robustness and quality.

Sponsor actions

Actions taken:
29/1-2025: Immediate suspension of subject inclusion at the site until further notice.

Planned actions:
* All subjects who received a dated version of the "deltagerinformation" will be contacted and informed of the serious breach. All will be offered verbal and written information once more with the latest version of "deltagerinformation", and informed consent obtained once more.
The subject will be offered withdrawal of their informed consent and all their data deleted.
If a subject is deceased all data will be deleted and not be part of the clinical study report.
If a subject cannot be reached all data will be deleted and not be part of the clinical study report.
Timeline: First contact to the subjects will be within one week of this notification.

* Sponsor will visit the site and go through all trial documents, review data, perform a root cause analysis, determine if other issues exist, and evaluate the extent of the issues. Subject inclusion cannot and will not continue as long as this process goes on.
In subjects where data reliability or robustness is comprised (for instance if eligibility cannot be verified), data will be removed from the clinical study report.
Once all causes and issues have been identified, solutions will be discussed with the site which may include renewed training of trial personel, revision of SOP etc. If a feasible solution cannot be found, the sites will be closed and removed as a trial site.
If a feasible solution is agreed upon, sponsor or sponsor's representative will visit the site every other week in the first three months are inclusion is resumed to ensure protocol compliance and the subjects' rights.
Timeline: Visit to the site will be within two weeks of this notification. Principal investigator at the site is currently on leave - possible solutions will be discussed once the PI returns (in 3 months).

* Sponsor will visit all remaining trial sites to ensure the study is carried out according to the protocol, subject rights are protected and similar breach does not occur at other sites.
Recent GCP monitor visit have verified, that all other sites use the correct "deltagerinformation".
Timeline: Within four weeks of this notification.

* Critical revision of standard operating procedures (SOP) related to data registration and trial conduct. Any revised SOP's will be sent to trial sites and completeness of TMF and SOPs will be checked at trial visits (see above)
Timeline: Within one week of this notification.