What is it? Why is it important?
Central monitoring is a remote evaluation of study data carried out at a different location from where the study is conducted.
When data are captured electronically in an internet-based eCRF, the monitor, statistician, or medical reviewer can remotely access and evaluate study data.
For any remote monitoring, data must:
- Be available on eCRF
- Lack participant identifiers such as, name, DOB, address
- Be stored in a database that allows access based on individual and personalised access rights
Centralised monitoring that includes statistical data analysis 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?
- Define data checks that can be performed remotely, such as data completeness, plausibility, consistency checks, including checks for outliers (e.g. unexpected data based on its normal distribution)
- Include checks of important data (e.g. data related to the primary endpoint)
- Define 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
Centralised data monitoring:
- Can complement and reduce extent and/or frequency of on-site monitoring, and can thus be more cost-effective
- Can be performed without having to inform the site
- Does not exclude site communication, as the monitor can discuss issues detected during centralised monitoring (e.g. by phone or email)
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 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, Clinical Trials Unit, CTU, dkf.unibas.ch
Bellinzona, 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.ctc.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