The monitoring process

1. The monitoring process

2. Stages of a monitoring visit Before the visit During the visit After the visit

3. During the visit • The monitor will assess or discuss: • Site, staffing, research labs or other facilities • Regulatory file and study records • Clinical procedures if possible or appropriate • Any problems and issues identified • Debrief at end of visit

4. After the visit • The monitor will • Complete site visit report • Submit the report to the sponsor • The sponsor will: • Distribute site visit report to the site

5. 4 types of monitoring visits: Site assessment(pre trial) Site initiation Routine(interim) visits) Close out visit

6. Pre study visit Purpose : • It’s a face to face meeting with the investigator to explore the overall feasibility of the site and the investigator to participate into the study. May be combined with the study initiation visit.

7. Site assessment

8. Study initiation visit Purpose: - to uniformly provide study specific information to investigator(s) and study staff prior to study start up. - reassess resources and capability to conduct a research study.

9. Study initiation(cont) • The monitor will meet with the study staff to discuss research obligations under GCP: • Investigator administrative responsibilities • IRB approvals and communications • Regulatory file requirements(ICH GCP E6 8.2) • Informed consent forms and process • Protocol and protocol amendments • Source documentation • Study product handling and accountability • Safety reporting • Protocol specific training • Archiving of study documents

10. Study initiation (cont) • The monitor will • Review sponsor policies , standards and procedures for the conduct of clinical trials. • Reassess the site facilities • Provide additional guidance to the site as determined by his/her findings. The better the site initiation, the better the site performance.

11. Interim monitoring visits Purpose: • Protection of human subjects rights and wellbeing. • Accuracy, completeness and verification of reported trial data. • Trial conduct in compliance with protocol/amendments, GCP and regulatory requirements.

12. Interim visit (cont) • Review /assess the following: • Enrollment status, rate and any drop outs. • regulatory files • CRF’s, source documents, informed consents, AEs/SAEs/SUSARs • Study product • Protocol and regulatory compliance • laboratory review • clinical operations • Follow up on previously identified issues • Debrief

13. Source data verification process Source data: • all information in original records and certified copies of original records of clinical findings, observations or other activities in a clinical trial necessary for the reconstruction an evaluation of the trial. (ICH GCP1.51) Source documents: • original documents, data and records(e.g. hospital records, lab notes, clinical charts, subjects diaries, pharmacy dispensing records, x-rays, subject files etc) (ICH GCP 1.52)

14. SDV process(cont) • SDV: evaluation of the conformity of the data presented in CRFs with source data. • Main aim: confirm that the data collected is complete, accurate, reliable and verifiable so as to give confidence to sponsor and regulatory authorities in the data being used to support a marketing application. • Without SDV, no scientist can have confidence in data presented and conclusions derived.

15. SDV process (cont) Key data : • 10 efficacy data • Inclusion/exclusion criteria • Medical/medication history • Physical exam/vital signs • visit dates • Adverse events • Concomitant medication • Record that patient entered clinical study and date of IC Any gross errors in these might be detrimental to the scientific and ethical quality of the clinical trial.

16. SDV process(cont) • Methods of SDV: • Back to back • Direct method- monitor has direct access to source data (ICH GCP E6 1.21,5.15) • Extent of SDV ??? • Depends on: clinical trial phase, quantity of data, time availability, man power availability, investigator research experience, company policy,

17. SDV process (cont) • Common approach: • Critical data: focal to aims and objectives of study and must be correct. • Informed consent to participate • Clinical notes • Conformance to inclusion/exclusion criteria • Primary efficacy endpoints • Secondary efficacy endpoints • Recording and reporting of SAEs • Documentation that that study drug was prescribed and at the specified dosage • Visit dates as per protocol • Non-critical data e.g. very neat, high numbers of overwriting, rapid recruitment, lack of SAEs when they would be expected etc.

18. SDV process(cont) • CRF content review: • Missing, incomplete or illegible entries, signatures or dates • Data recorded in wrong fields • Illogical, inconsistent or ambiguous data • Data omissions • Entries demonstrating failure to follow protocol • Inaccurate calculations • Inadequate documentation of corrections

19. SDV process(cont) • Common problems • Data entered directly to CRF • Brief medical history/ scanty clinical notes • Several volumes of SD • SD/CRF mismatch • Illegible handwriting • Maximum acceptable error rate • Document the SDV process • SD examined • CRFs checked and why they were selected • Critical and non-critical data items checked • Nature and frequency of errors • Any corrective actions undertaken

20. Informed consent documents • What to check: • Each participant has personally signed and dated ICD prior to study procedures. • Appropriate use of independent witness • Correct version being used • Names of subjects/person giving consent, date and time • Investigator appropriately signed ICD and dated. • All pages of ICD present