A CRA could be employed directly by the sponsor companies (Pharmaceutical, Biotechnology or any research company) of clinical trials or by Contract Research Organizations (CROs) also referred to as Clinical Research Organizations (As per ICH GCP) that conduct clinical trials on behalf of the sponsor companies. Let’s learn about the types of clinical trial site visits conducted by CRA.
The main responsibility of CRA is to make sure that the rights, safety and well-being of subjects participating in clinical trials are protected. A Clinical Research Associate (CRA) acts because the main mode of communication between sponsors and therefore the site.
Clinical Research Associate (CRA) qualifies, initiates, monitors, and closes the clinical test sites assigned to him/her. Based on the extent of experience, CRAs are often hired at CRA Level I, II, and III, Senior CRA by employers.
Some common on-job responsibilities of CRA’s are:
- Conduct Visits and monitor clinical trial sites to verify that ICH GCP guidelines, study protocol, and applicable regulations are being followed
- Preparing site visit reports within the stipulated time
- Creating, develop, and write trial protocols presenting for the steering committee.
- Identify the suitable facilities to use as the clinical trial site.
- Set up trial sites and it has responsibility each centre has the trial materials including the trial drug often known as the investigational medicinal product.
- Archive study documentation and correspondence
- Prepare final reports, SOP.ICH, GCP guideline.
- Make sure that only qualified, delegated individuals are working as site staff which they’re adequately trained
- Ensure data collected is accurate and verifiable and inline with ALCOA
- Manage clinical test site payments and handle any ongoing negotiations
- Make sure that the location has acceptable infrastructure which it continues to stay so throughout the study
- Act as a mentor to site staff and supply continuous support and guidance
- Ensure appropriate filing of study documents, Site Investigator file, and archival
Listed skills are required as a Clinical Research Associate (CRA).
- Understanding of the drug development process with knowledge of ICH-GCP and relevant regulatory guidelines
- Communication skills
- Ability to work under pressure
- Multi-tasking ability and travel
- Ability to work independently
- Effective problem-solving skills
- Decision-making ability
- An eye for detail and verification
How Clinical Trial Outsource and Flow process takes place?
- Contracting Signed by CRO, Sponsor & investigator
- Design, Development of Protocol & Informed consent
- Protocol, Informed Consent, Source Documents Approval, Letter from IRB and regulatory
- Patient Recruitment, Advertising & Marketing, Patient Participation, Pre-screens, Qualifying, scheduling, Exams, Monitoring, Follow-up Visits, and Calls, Data Entry, Review for Accuracy IIIStatistical Analysis, Analyzing the Data Completion of Study Summary, Summary Forwarded to Sponsor, Data filed and stored, Study Closed.
I am listing Types of Clinical Trial Site Visits conducted by CRAs. This may vary depend on industry practices.
Site Qualification Visit
The site qualification name itself indicates the qualification of the hospital site. CRA has to confirm whether the hospital infrastructure and setup are qualified/capable to conduct the clinical trials.
This visit also referred to as Site Selection Visit (SSV) or Pre-Study Qualification Visit (PSQV). The CRA will usually request a tour of the hospital and time to discuss the fundamentals of the protocol and how that relates to the feasibility of recruiting potential participants.
The sponsor representative (CRA) time to discuss the basic rules of the protocol and the way it’s associated with the feasibility of recruiting potential participants with the site staff. The qualified Investigator and Research Coordinator are responsible for providing the required information to the sponsor.
Other topics of discussion during the SQV include:
- Investigator responsibilities
- Qualifications of the investigator or other site personnel
- Study objectives, endpoints, indication challenges, inclusion-exclusion criteria, protocol-required procedures, eligibility criteria, and patient recruitment
- IRB (e.g., informed consent requirements)
- Adverse event reporting, source documentation, and record retention
- Infrastructure, availability of a storage area to store investigational drug or devices, and availability of required equipment or instruments
- Reporting of the event, documentation source.
As a representative of a sponsor to the institution that is fully capable and equipped to make a specific clinical trial. SQV performs after feasibility Assessment (To evaluate the possibility to conduct a clinical trial in a proposed location based on a list of questions. The assessment will allow the sponsor and qualified PI to make a decision regarding the feasibility of the study at his/her site).
It is a 1-day visit. After the site qualification visit, CRA will prepare the SQV report and it will be reviewed by the project manager. CRA may ask for all the relevant documents from the site to verify the documents. Upon finalization of SQVR, CRA will share the follow-up letter along with the site selection letter (whether selected/rejected) for the clinical trials.
Site Initiation Visit
The site initiation visit (SIV) is completed by the Sponsor/CRA prior to the start of the patient recruitment at the hospital site. In the time of SIV, the Sponsor ensures that the Investigator team has all the required resources and it’s able to conduct the human subject research conducted supervisor an Investigational New Drug Application (IND). It takes a 2-day visit.
Site initiation visits conduct prior to site activation for recruitment and specific protocol. These visits have several goals depend on the initial or interim visits: To train site staff on the protocol and study related processes; to confirm readiness for study implementation, and to identify additional requirements that must be satisfied prior to site activation and subject recruitment.
The SIV ensures the investigator is aware of its responsibilities with the clinical protocol and the primary investigator, sub-investigators, and site staff is well known with the study documentation, investigational product management, and administrative procedures.
How CRA conduct the SIV?
We discuss about the Site Initiation Visit in the following
a. Background and purpose of the study, including study objectives and style
b. procedures of the study
c. Investigator’s Brochure (IB) or Device Investigational Plan (device description section), or reference product label.
d. Investigational product(s): Pharmacological or technical aspects of the product(s), management and accountability utilizing an investigational product accountability log
e. Recruitment of subject and screening, including criteria for inclusion and exclusion
f. Obtaining consent
g. All essential documents such as case report forms (CRFs), consent forms, etc.
i. Adverse Event/Adverse Device Effect Reporting
j. Data collection and record keeping
NOTE – No hospital can initiate any trail without a site initiation visit. It is compulsory for any requirement initiation.
Site Monitoring Visit
The act of overseeing the progress of a clinical trial, and of ensuring that is conducted, recorded, and reported in accordance with the protocol, Standard Operating Procedures (SOPs), Good Clinical Practice (GCP), and the applicable regulatory requirement(s).
CRAs Schedule all monitor visits, including the first visit following initial enrolment or periodic visits throughout the study. When possible then the next monitor visit should be scheduled at the conclusion of the current visit. CRA shall share the Monitoring visit confirmation letter to the site with the monitoring agenda to ensure appropriate key research personnel will be available as needed (for example- PI, CRC, research nurse, pharmacist).
CRA ensures all regulatory documentation and case report forms (CRFs) are completed and available for review. Ensure all unanticipated problems, adverse events as defined within the protocol and protocol deviations are reported to the sponsor and therefore the IRB.
CRA also assure that the Investigational product is securely stored according to the instructions in the protocol example temperature or light specifications and all accounting records are updated.
Post the Monitoring visit, CRA shall prepare a monitoring visit report. CRA should ensure any outstanding items/issues are addressed in a timely manner and the necessary information is provided to the sponsor and/or project manager. Provide outstanding item resolution and document resolution in the study files.
After the finalization of the report, forward the PI a copy of the monitor visit follow up letter, if not already done so by the monitor, and inform them of the plans to address any outstanding issues identified during the visit. CRA shall File the monitor visit confirmation letter, report, and follow up letter in the regulatory binder.
Monitoring Report: A written report from the CRA/Monitor to the site after each site visit and/or other trial-related communication according to the sponsor’s/CRO SOP.
Regulatory Binder: Binder or set of the file which is used to organize/store essential study documents.
Site Close-out visit
Closeout activities ensure that the studying procedure, all regulatory documents and data are 100% completed, and any Investigational Product (IP) or supplies are returned or destroyed with documentation of the details pertaining to the destruction. It is important that the Principal Investigator (PI) is available to sign off all the documents required for the closeout to be completed.
A close-out visit will occur once subjects are not any longer being dosed, all the info is collected, the database is locked and prepared for statistical analysis, and therefore the study conduct has ended.
The whole concept of the close-out visit means it is to make sure that everything is neat and tidy at the study site which the documentation is well organized and can remain intact and be accessible within the future as required for regulatory reasons.
A sponsor or the FDA should be ready to return to the place of study conduct years later and re-create exactly what occurred in the least points during the trial by reviewing the regulatory documentation, subject and source documentation, full medical charts, and the other applicable study records.
Documentation is everything in our industry and that we are always saying, “if it isn’t documented it didn’t happen.” If thorough and accurate records aren’t maintained, the PI cannot prove that the study was in accordance with the protocol and all applicable regulations and that subject safety was adequately monitored by the conduct of the trial.
These are the basic understanding of the Types of Clinical Trial Site Visits which are conducted by CRAs. I will write down in detail about each visit. Stay tuned.
Article By : Shahenaz Karadesai