Stephen Cropper, Senior Clinical Research Associate, Clinical Operations, PROMETRIKA, LLC
Clinical trials leverage the expertise of people in a wide variety of roles — researchers, project managers, clinical data managers, etc. One of the positions with which people may be less familiar is that of the clinical research associate (CRA). CRAs play a critical, if somewhat unheralded, role in the success of a trial.
What is a Clinical Research Associate?
A CRA is an observer, documenter, and conductor of a clinical trial. However, the CRA’s responsibilities and title can vary widely depending on the need of the sponsor. Some of the titles that identify CRAs are:
- Clinical Monitor
- Lead CRA
- Clinical Trial Specialist
- Site Manager
CRAs need to be prepared to travel regularly because they visit study sites frequently. They need to thrive while working independently, as they often work by themselves, and they must have well-honed skills in planning, organization, and preparation to maximize the effectiveness of their site visits. In addition, CRAs need to be flexible and creative, as the role is one that involves juggling many tasks, being the intermediary for different study participants or stakeholders, and, in some cases, meeting tight deadlines.
CRAs must have a comprehensive understanding of a trial and the people involved, as they may be required to interact with anyone on the team. This can include project managers, data managers, investigators, pharmacists, biostatisticians, safety experts, CRA managers, and others.
What Tasks do Clinical Research Associates Perform?
CRAs have responsibilities that cover the full lifecycle of a clinical trial, which starts with pre-study qualification visits (PSQVs). The CRA travels to study sites to assess whether the site has the necessary experience and resources for working on the trial, an acceptable number of eligible patients, appropriate and available clinic space, the equipment that may be necessary for the trial, security for keeping records inaccessible to non-study personnel, and regulated drug storage areas. Next, site initiation visits (SIVs) take place as part of the kick-off of the trial. At these visits, the CRA trains the team members at the site to understand what their responsibilities will be, and to officially green-light the start of the trial.
Over the course of a study there will be periodic interim monitoring visits (IMVs) at the participating sites. Generally, the goal is to have the CRA onsite at least once every four to eight weeks, depending on the rate of enrollment and complexity of the study objectives and assessments. The CRA will review study progress, the quality and accuracy of data collection, compliance of patients to trial visits and assessments, and investigational product accountability, and will ensure good clinical practices are maintained throughout the trial and offer direction when needed. At the end of the trial, a close out visit (COV) occurs at the site to address any unresolved study issues, ensure the site has properly informed the ethics committees of the completion of the trial, help document the end of a site’s participation, and collect study-related items for a sponsor when the study is complete.
Regardless of the type of visit, when a CRA is at a trial site there are many study-related activities that may occur. Some specific examples of monitoring tasks include:
- Enrollment process and standards. Is the site enrolling qualified participants?
- Informed consent procedure. What process is being used to obtain and manage properly-completed consent forms?
- Protocol adherence. Are any deviations from the protocol taking place?
- Data entry. Is the site entering data completely, accurately, and in a timely manner?
- Medication distribution. Is the site carefully managing and distributing the study medication?
- Regimen compliance. Are subjects complying with the medication regimen that they have been assigned?
- Query response. Does the site answer questions promptly?
- Regulatory compliance. Are the necessary legal and regulatory documents completed correctly and filed?
- Adverse event reporting. Are all adverse events being properly logged and reported? Are serious adverse events being sent to the Institutional Review Board (IRB)?
When not onsite, CRAs have a wide range of tasks they must complete related to a trial. For example, they write pre-study visit letters, visit reports, and follow-up letters for each site visit that detail the progress at that site and list any recommendations for improvement. Remote monitoring is done to ensure the site is keeping up with data entry and is resolving queries in a timely manner. Listings are reviewed to look for data trends that may be missed during rigorous source-to-CRF data comparisons.
Ultimately, CRAs must wear many hats to help ensure the study produces valid and meaningful results. On any given day, they may serve as a negotiator, drug auditor, communicator, trainer, and motivator, just to name a few of the roles. The importance of the CRA position in the community of professionals working in clinical trials cannot be overstated.
Challenges in an Evolving Industry
As our industry evolves, CRAs face many new challenges. Reporting is one area where changing expectations are requiring CRAs to adapt. Sponsors increasingly want more visit details in the body of a report, even though the FDA may not require them. This is a change from the past, when sponsors had fewer requirements. Unfortunately, these new requirements can affect efficiency and impact the cost of the trial.
The move toward electronic content and the idea of an “eRegulatory” approach is also relatively recent. Historically, each trial site had a binder that held all the administrative study documents. Today there are software packages that allow sponsors to collect and review regulatory, and other, trial documents instantly. While technology has its advantages, there will likely always be a need for paper documentation, in some capacity. CRAs must learn to merge the two approaches and become adept at using electronic trial management files (eTMFs) and records information management (RIM) procedures.
Another change is that sponsors and clinical research organizations (CROs) are building electronic forms that allow for more legible communication compared to handwritten documents. The use of electronic forms also allows senders to precisely track the receipt of a form, which might have been lost in the past when information was communicated via documents that were faxed or emailed.
Onsite monitoring versus remote monitoring is an additional area of evolution in our industry that affects CRAs. As more hospitals develop online portals that site monitors can use to access data, there is a move toward this more efficient web-based form of observation. However, it remains to be seen whether the efficiency gains justify the loss of the human connection that comes from face-to-face visits.
The Glue that Holds a Clinical Trial Together
While it may not be the most flattering metaphor, it is fairly accurate to think of CRAs as the “glue” that holds studies together. A CRA’s contribution to the success of a clinical trial may not be the most visible, but it is certainly significant. It is important that sponsors, CROs, and study sites recognize the key role these team members play and strive to give them the time, resources, and support they need to help ensure that the study program achieves its objectives effectively.