Good Clinical Practice guidelines (VICH GL9) Section 8.3.1 requires that all raw study data, “whether handwritten or electronic, be attributable, original, accurate, contemporaneous, and legible.”
“Original and accurate means the raw data are the firsthand observations.”
“Contemporaneous means the raw data are recorded at the time of observation.”
“Legible means the raw data are readable and recorded in a permanent medium , e.g., ink for written records or electronic records that are unalterable.”
Section 5.2.9 requires that “all data are correctly and completely recorded ,” and Section 5.2. 1 O stipulates that “illegible , missing, or corrected study documentation is fully explained.”
Almost anyone reading these guidelines can imagine data entries that would not comply with one or more of the parameters listed above. To draw those entries into compliance, data reviewers issue requests for correction or clarification, otherwise known as “queries.”
Robust study training, reinforced during each monitoring visit, can reduce the total number of queries in a study. (Please see my article, “Be Query Wary … or Query Weary … Your Choice,” AnimalPharm 28 August 2013, which highlighted best practices regarding data accuracy, as well as a suggestion for enhancing training.) However, some study investigators, being human , forget some of their training, lose some of their enthusiasm, or just get careless. That’s when the queries start to rise.
Ironically, some of the simplest, shortest data entries generate the highest percentage of queries in almost every study. Common examples are the gender and date of birth of the study subject, the last name of the subject’s owner (who sometimes gets married or divorced), correct dates entered in a format different from that specified in the study protocol, out-of-range lab results that may or may not be clinically significant, and changes from baseline observations.
To maintain study momentum , as well as identify problems or areas needing remedial training, data reviewers should issue their queries as soon as possible. This prevents situations in which the investigator cannot clearly remember the event or observation that generated the query. And, to minimize the number of follow-on queries for additional information or clarification, data reviewers should make their queries as specific as possible, both as to the issue being queried and the type of response desired.
To demonstrate these concepts, perhaps a few good … and bad … examples from actual studies might help.
Query: It appears that the blood pressure reading was outside the normal range. If you agree, please complete an adverse event report:’
Response: While the blood pressure reading was outside the normal range, it is not clinically significant for this cat. AE report completed:’
The investigator answered the query, explained his reasoning , and took appropriate action.
Query: The recorded time of assessment is missing. If it was recorded on paper, please transcribe the time as a late entry and then upload the source document.
Response: We could not connect to the internet at the time of this assessment and recorded the time on the paper data form, which has now been uploaded. A Note to File has been completed to explain why the assessment time was not recorded in the EDC contemporaneously.
The investigator explained why the assessment time was missing on the eCRF. She also noted that the time had been recorded contemporaneously on a paper CRF, which she uploaded to the EDC system once her internet access was restored. She then documented her actions in a Note to File to complete the record.
Query: Please explain if the ingredients of this concomitant medication are contraindicated.
OK, what? The investigator should check the ingredients of the subject’s concomitant medication against the inclusion /excl usion criteria in the study protocol and give a detailed response. In this case, since the medication was contraindicated, the subject was removed from the study and the investigator completed a protocol deviation report. The investigator was directed to immediately review the protocol’s inclusion/exclusion criteria, and the study monitor conducted remedial training of the investigator and participating site staff during the next site visit.
Query: Please confirm the date of this visit. It appears that it was completed after study termination.
Response: The visit was completed before study end.
Follow-On Query: Please correct the date of the visit.
Response: Matilda is a female.
For this one, the study monitor did not know whether to laugh or cry. This site had been problematic throughout the study. Fortunately, this was the last set of data forms for the last subject at this site. No one was surprised when this investigator was not considered for the next study.
The issuance and resolution of queries is an essential component of quality data. As such, it should be an important part of study training so that each investigator knows to expect them and, more important, knows how to answer them correctly.