In Clinical Trials, Clinical Research Associate (CRA) is the primary representative who monitor whole trial process on regular basis. ICH-GCP use a term “Monitor” instead of Clinical Research Associate (CRA). CRA is also called a trial monitor, clinical monitor, medical monitor as per company defined designations. CRA work for Sponsor, Contract research organization (CRO) or any academic institution conducting clinical trials.

If you read Federal Regulations 21 CFR 312.53 and ICH-GCP 5.18.2, these two sections are specially for Clinical Research Associate or Monitor.

As per Federal Regulations 21 CFR 312.53 (d), “Selecting monitors. A sponsor shall select a monitor qualified by training and experience to monitor the progress of the investigation.”

ICH-GCP 5.18.2 (b), “Monitors should be appropriately trained, and should have the scientific and/or clinical knowledge needed to monitor the trial adequately. A monitor’s qualifications should be documented.”

Purpose of clinical research associate  (CRA)

We know that CRA play an important role in any clinical trial and he/she is the direct representative from sponsor or CRO. CRA is the main responsible person who work as a communication wire between trial Investigator and sponsor or CRO. Now below point will give you some idea about the purpose of CRA and why sponsor appoint CRA.

  1. The rights and well-being of human subjects are protected
  2. The reported trial data are accurate, complete, and verifiable from source documents.
  3. The conduct of the trial is in compliance with the currently approved protocol/amendment(s), with GCP, and with the applicable regulatory requirement(s).

Selection and Qualifications of Monitors

  1. Monitors should be appointed by the sponsor.
  2. Monitors should be appropriately trained, and should have the scientific and/or clinical knowledge needed to monitor the trial adequately. A monitor’s qualifications should be documented.
  3. Monitors should be thoroughly familiar with the investigational product(s), the protocol, written informed consent form and any other written information to be provided to subjects, the sponsor’s SOPs, GCP, and the applicable regulatory requirement(s).

Role and Responsibility

Clinical Research Associate or Monitor should ensure that trial is conducted and documented properly with all rules and regulations. In some cases, site facility is not following all rule and regulations and they are doing manipulations which is not correct and in whole process participant is directly affected. In that time monitor is the responsible person who check and rectify all the issue and inform sponsor regarding all these problems. Below are some role and responsibilities of Monitor:

1. As I already told you above, CRA or Monitor act as main line of communication between sponsor and investigator.

2. Verify the Investigator qualifications, resources, laboratories, facilities, staff etc.

3. Verify Investigational products:

  • Storage time, conditions, and supplies
  • Investigational products should be directly supplied to subject involved in trial with protocol specified dose
  • Subject receive proper instructions, How to use, handle, store and return Investigational products
  • All Investigational Products data should be documented in trial site
  • disposable of Investigational products in trial site should be complies with applicable regulatory requirement and as per sponsor instructions

4. Verify that Investigator should follow protocol Instructions and all approved amendments, if any.

5. Verify that Informed consent should be received before subject’s participation in clinical trial.

6. Verify that Investigator have received Investigators Brochure, document and all trials related supplies according to regulatory requirements.

7. Verify that Investigator and Investigator staff informed about the trial.

8. Verify and monitor that Investigator and staff is performing each and every trial task as per protocol and any written agreement between sponsor and Investigator or Institution.

9. Verify that Investigator or site coordinator enrolling only eligible subjects as per protocol requirements.

10. Verify that Source document and other trials related document are accurate, complete and up-to-date.

11. Verify all documents provided by Investigator are complete, well maintained, up-to-date, accurate.

12. During the trials Monitor reports enrolled status or rate to sponsor.

13. Verify the completeness and accuracy of CRF entries, source documents and other trials related documents. like

  • Data capture as per protocol and consistency with source document
  • Any dose modification are recorded or not and well maintained for every subject
  • Adverse events, Concomitant medications and other illnesses are reported as per protocol
  • Subject visit failed, test not conducted, any examination not performed should be recorded as per protocol
  • Any withdrawal and dropout of trial subject recorded and explain in CRFs

14. Informing Investigator related to any errors, omission and any other modifications.  Then Investigator or Authorized staff check all the details rectify the issue and Initialize the CRF changes.

15. Verify that all adverse events are reported within the time period given by ICH-GCP, the sponsor, IEC/IRB, protocol, and any authorized regulatory requirement.

16. Verify that Investigator is maintaining all the essential documents related to trial. (See Section 8 of ICH-GCP: Essential Documents for the Conduct of a Clinical Trial)

17. Inform Investigator related to any deviations from the protocol, SOPs, GCP and Investigator should take action to rectify all issues.

Monitoring Procedures

If we talk about the monitoring procedure by Clinical Research Associate or Monitor then this is very simple. CRA or monitor is not doing any change and modifications from their side. Every thing is mentioned in protocol and SOPs provided by Sponsor.