Development↦Monitoring↦Montoring Strategy↦Central Monitoring
What is it? Why is it important?
Centralised monitoring is a remote evaluation at a location other than the site(s) where the study is being conducted. Centralised monitoring includes the following activities:
- Remote/off-site monitoring: The monitor checks study documents (copies) provided by the site, and/or discusses relevant study procedures. Provided documents must not contain any participant identifiers (e.g. name, DOB, address). Discussions are held via phone or during conference calls
- Central data monitoring: The data monitor, statistician, or medical reviewer remotely accesses and evalautes study data. This is greatly facilitated when data is captured electronically (e-CRF)
For data protection reasons, regulators do not normally allow for the central monitoring of participant medical records since the complete de-identification of documents is considered too challenging.
Central data monitoring that often includes statistical data analysis (e.g. called central statistical monitoring) can be used to identify:
- Missing, implausible, or inconsistent data
- Unexpected or false data (e.g. outliers)
- Systematic errors in data collection
- Trends and inconsistencies (e.g. an unexpected lack of variability)
- Variability within and across sites (e.g. identification of sites with high error rates, relatively high or low number of (serious) adverse events, low participant recruitment)
- Study protocol deviations (e.g. changes in participant visit schedules, specific tests, or medical examinations that were not – or only partly – performed)
- Deviations from database completion requirements (e.g. entry must be done within 5 days after participant visit)
Sites with poor performance or problematic issues detected during centralised monitoring might best be solved by performing an on-site visit.
In a multicentre study, 4 of the 5 participating sites reported headaches in at least 30% of the participants. At one site with 50 participants, no headaches were reported. This raises concerns regarding site adherence to study safety reporting requirements. This issue, which was detected remotely, may trigger on-site visits to investigate the root cause and to impose corrective measures.
What do I need to do?
As a monitor define remote/off site monitoring tasks such as:
- Study documents to be reviewed remotely (e.g. copies of site delegation-log, drug accountability-log, IMP/MD storage temperature-log)
- Study procedures to be discussed (e.g. participant consenting procedures, exclusive use of EC/RA (e.g. Swissmedic) approved documents, adherence to safety reporting requirements)
Define central data monitoring tasks such as:
- Study data checks that can be performed remotely, such as data completeness, plausibility, consistency checks, including checks for outliers such as unexpected data based on its normal distribution
- Checks of important data (e.g. data related to the primary endpoint)
- The statistical monitoring approach with support from a statistician. Especially in multicentre studies, inter-site comparisons can provide additional information
For more information refer to Data Handling in this Study Guide
- Can be more cost-effective, as it can be used to complement and thereby reduce the extent and/or frequency of on-site monitoring
- Is particularly important in multicentre studies as it helps keeping oversight regarding the conduct and performance of study sites. The implementation of central data monitoring is thus highly recommended in large multicentre studies.
Certain aspects can only be monitored through on-site monitoring and not through centralised monitoring, such as checking:
- ICFs, to confirm that all recruited participants have dated and signed the document
- Medical records, to verify that:
- eCRF entries are correct. This process is also referred to as SD verification
- Participants fulfil study inclusion and exclusion (e.g. eligibility) criteria
- Procedures, to confirm that study drug preparation, storage, and inventory are correctly handled and monitored
Include the option of on-site monitoring visit(s) in your monitoring plan, especially if irregularities or problems are identified as a result of centralised monitoring.
Where can I get help?
Your local CTU↧ can support you with experienced staff regarding this topic
Basel, Departement Klinische Forschung, CTU, dkf.unibas.ch
Lugano, Clinical Trials Unit, CTU-EOC, www.ctueoc.ch
Bern, Clinical Trials Unit, CTU, www.ctu.unibe.ch
Geneva, Clinical Research Center, CRC, crc.hug.ch
Lausanne, Clinical Research Center, CRC, www.chuv.ch
St. Gallen, Clinical Trials Unit, CTU, www.kssg.ch
Zürich, Clinical Trials Center, CTC, www.usz.ch
ICH GCP E6(R2) – see in particular guidelines
- 5.18 Monitoring activities
- 6.10 Access to source data / documents
ISO 14155 Medical Device – see in particular section (access liable to costs)
- 7.8 Document and data control
- 9.2.4 Monitoring