Clinical Research Associates (CRAs) are essential members of research teams and play a crucial role in clinical trial monitoring. 

A CRA is a liaison between a study Sponsor or Clinical Research Organization (CRO) and the study sites. An article on MHA Online says a Clinical Research Associate’s role is critical in ensuring that the Sponsor or CRO does not influence study results. 

Along with keeping results transparent, CRAs ensure data integrity so the medications, devices, and procedures being studied are safe and effective. CRAs are responsible for documentation, organization, and effective communication to ensure this accuracy. 

Most Clinical Research Associates are simultaneously involved with multiple clinical trials, and the typical daily responsibilities differ depending on the stage. Of course, the best CRAs are adept at any clinical trial stage, which comes with experience. Understanding the tasks outlined in this article will help.

What does a CRA do during Study Start-Up?

CRAs can start their work on clinical trials during Study Start-Up (also called Study Initiation) months before a patient consents to the trial. 

One of the initial tasks for a CRA in this stage is to conduct Site Selection Visits (SSV) to qualify potential study physicians and study sites for participation in the trial. During an SSV (also called Site Qualification Visit (SQV) or Pre-Study Qualification Visit (PSQV) or Site Evaluation Visit (SEV)), CRAs ensure the site has all necessary personnel, equipment, and access to the participant population under study by reviewing the site’s feasibility questionnaire, providing a high-level summary of the study, and taking a facility tour. 

According to this article on Applied Clinical Trials Online, 70% of clinical trials have a start-up delay, and 80% of studies don’t meet their initial target enrollment. CRAs can decrease these percentages by ensuring optimal sites are selected for the trial.

Necessary Assessments at a Site Selection Visit

Here are six areas for a CRA to assess at an SSV*:

*Depending on the study and direction from the study team, additional areas may be reviewed by the CRA during the SSV.

1. Staffing

• Does the site have enough qualified staff? Are backup staff available as needed?
• Is the staff equipped with the necessary credentials?
• What is the staff’s experience level in Clinical Research and with the indication of the study?

2. Facilities 

• Is there ample space in the facility to carry out the study and store supplies?
• Does the site have the equipment needed? 
• Is the equipment functioning correctly and are calibration records available?
• Are there secure and limited access areas where the Investigational Product will be stored?

3. Site Information

• Can the site use a local or central Institutional Review Board (IRB)?
• If a local site, when is the next IRB meeting? 
• What is a typical timeline for contract and budget negotiations?
• Can the site start working on regulatory documents simultaneously with contract and budget negotiations?

4. Documents

• Does the site have Standard Operating Procedures in place?

5. Recruitment

• How does the site plan to recruit for the study?
• Does the site have experience with recruiting similar patients?
• What resources will the site use for outreach and patient recruitment?
• Is the site involved with any ongoing trials with the same indication?
• How does the site plan to manage patient retention?

6. Previous Experience

• What is the site’s history with prior clinical trials with a similar indication?
• What issues has the site had in past studies, and what has been done to rectify the problems?
• In what ways has the site been successful with other research trials?

Following the Site Selection Visits, the CRA writes a report for the Clinical Trial Manager (CTM) and Sponsor that details site findings and their final recommendation for the site visited. 

After a site is selected, the CRA may assist with questions on the site’s regulatory documents, contract/budget, and IRB submission. 

What does a CRA do during Study Conduct?

Once sites are selected during Study Start-Up, the trial then enters the Study Conduct (Study Maintenance) stage. This is typically the busiest stage for Clinical Research Associates. 

Although the number of clinical trials that use remote monitoring is increasing, many CRAs spend a lot of time traveling to sites for Site Initiation Visits (SIVs) and routine monitoring visits (RMVs). 

Site Initiation Visits 

Clinical Research Associates conduct SIVs with sites selected to conduct the clinical trial. During an SIV, the CRA educates the site team about the protocol and helps get the site ready for the study to begin.

Here are eight responsibilities a CRA needs to complete at a Site Initiation Visit:

1. Provide study training to all delegated staff.
2. Ensure all trial IRB approvals are in place.
3. Verify the receipt of the Investigational Product (IP) and other study supplies.
4. Review source templates for accuracy.
5. Review regulatory documents for completion.
6. Assist with brainstorming pre-screening activities and ideas for patient recruitment. Here is a free download of proven recruitment strategies. 
7. Make sure all applicable staff have access to the appropriate systems, platforms, and passwords.
8. Answer questions.

PRO TIP: Take time to plan and prepare for the Site Initiation Visit! Here are four things a CRA can do before each SIV:

1. Download the slides to present on your laptop for easy access.
2. Practice your slides silently and out loud. Focus on the main points, and do not read the slides word for word.
3. Print a copy of the SIV Agenda and write the slide numbers from the presentation next to each agenda topic. E.g. the PI may only be available for 1 hour and you need to skip ahead to the PI relevant sections. Having the slide numbers already outlined on your printed copy of the SIV Agenda will help you quickly skip to the applicable slides and not waste any time!
4. Bring backup printed copies of all logs needed, including the Monitoring Sign-In Sheet, Training Log, and Delegation of Authority Log. This will enable individuals to sign the logs when they are present rather than spending time tracking them down afterwards.

The Site Initiation Visit lays the foundation for a successful start on the site level. When CRAs build relationships and effectively communicate with site teams, this contributes to a collaborative team environment.

Routine Monitoring Visits

Throughout the trial, the CRA will typically visit the site in person every 4-8 weeks, depending on the protocol and the site’s recruitment rate. If an on-site visit is not possible, the visit may be conducted remotely. 

Once a trial participant is enrolled, CRAs review patient data on the informed consent form, source for each visit, electronic case report forms (eCRFs), and medical charts to ensure there were no drug, device or safety issues reported. This ensures patient safety and data integrity.

Furthermore, CRAs monitor site activities to confirm the study protocol, International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH), Good Clinical Practice (GCP) principles, and local regulations are being followed. If a site is not meeting study standards or complying with the study protocol, the CRA implements action plans to get the site back on track.

Relationships between the CRA and the clinical staff are important during all stages of the study, especially at monitoring visits. Monitoring visits can be jam-packed, full days. However, when the visit is well-planned and the team works well together, more tasks can be accomplished, and more action items can be quickly addressed.

Many CRAs use time-saving tools to help increase their efficiency and productivity. For example, CRA Audit Notes make it easy to see the action items (especially urgent actions like SAEs or Protocol Deviations) that must be addressed. The CRA Audit Notes are more efficient than traditional yellow sticky notes often used. In addition, the Action Item Carbonless Pad is a way to list all action items in one place and keep team members on the same page.   

Click here for more tips about how to plan a productive monitoring visit.

What does a CRA do during Study Close-Out?

When a research trial nears the end, it moves to the Study Close-Out stage. One of the CRA’s primary responsibilities is to prepare their sites for database lock by completing source data verification for all study data at their assigned sites. Another critical responsibility during the Study Close-Out stage for CRAs is conducting a Close-Out Visit (COV) at their assigned sites. 

During a COV, the CRA ensures all activities at the site have been completed. A COV is typically a one-day visit scheduled and planned in advance. 

To maximize efficiency during Close-Out Visits, here are eight steps to help CRAs prepare:

1. Send a confirmation letter to the site. 
2. Confirm the meeting with the Investigator. Request the Investigator be prepared to sign the study logs during the meeting.
3. Ensure all queries are addressed and all patient casebooks are signed in the Electronic Data Capture (EDC) System. If not, add it to the Visit to Do List.
4. Discuss pending items with the TMF team, Sponsor, and Study Coordinator.
5. Contact the Safety team to confirm all queries are closed and any pending questions about specific safety events have been resolved.
6. Review the COV trip report to know what questions need to be answered.
7. Obtain mailing labels and instructions for returning supplies and IP. 
8. Prepare a “PI Speech” (i.e., what to discuss with the Investigator).

In addition to meeting with the Investigator to review study obligations, here are 11 tasks CRAs should complete at a Close-Out Visit:

1. Confirm all queries within the source documents have been closed or addressed.
2. Ensure documents are appropriately filed in the regulatory binder. 
3. Make copies of documents missing from the Trial Master File (TMF).
4. Complete study supply and IP accountability.
5. Collect a copy of the temperature logs for the entire time the IP was on-site.
6. Send back extra supplies if requested by the study team. 
7. Add the final number of unused kits from the site to the COV report. 
8. Disassemble extra lab kits (or instruct the CRC they may perform that task at a later date).
9. Discuss the management of the study samples with the study team. Confirm if a final shipment is needed or if retained samples at the site can be destroyed.
10. Review discrepancies by comparing the Interactive Voice Response Systems (IVRS) and the logs.
11. Verify that all study documents are maintained and stored at the site for the time specified in the study contract. Write the address in the COV report of where study records will be held. 

There is a lot to remember! Download this Close-Out Visit Checklist to help you stay on track and avoid missing important tasks.

Along with the other visits, following a Close-Out Visit, the CRA writes a report that includes the items reviewed during the visit, any discoveries while monitoring, and new action items. The report is then sent to the Clinical Trial Manager for review.

How can CRAs level up?

This article from MHA Online says the most successful Clinical Research Associates are detail-oriented, organized, multi-tasking, effective communicators who like variety in their work responsibilities and are interested in clinical research.

Clinical Research Associates have an essential role at each clinical trial stage. Their responsibilities vary depending on the study stage, but the best CRAs develop processes that enable them to be efficient and productive in each stage. 

CRAs can continue to level up in their career by learning or improving their skills – this could be learning new systems or becoming more proficient in the systems they use on a daily basis, such as MS Excel or MS PowerPoint. In addition, CRAs can also become certified through various Clinical Research Associations such as ACRP or SOCRA.

What long-term career option could a CRA consider?

After a few years in the CRA role, many CRAs transition to the Clinical Trial Manager (CTM) role to spend less time traveling and more time at home. Here is a free downloadable guide about transitioning to Clinical Trial Management and how to simplify the process and prepare for a promotion. 

If you are a CRA interested in preparing for the CTM role, the ClinEssentials All Access + LIVE CTM Training Course can help you stand out amongst other applicants. The course can be completed in as little as 6 weeks and teaches CTM responsibilities from Study Start-Up to Study Close-Out which are very different than the CRA responsibilities outlined at each stage in this article. Set yourself up for success so you can feel more confident and ready to take on the CTM role. Click here for more information about CTM Training. If you are ready to discuss taking your career to the next level and want to discuss the CTM Training course, book a call here.

Tiffany Ashton, MAS, CCRA, has over twenty years of experience as a Clinical Research Professional. Tiffany is the Director of Operations for ClinEssentials, a consultant in the Clinical Trial Manager role, and the expert instructor for the CTM Training Course.