Overview: Clinical Trial Roles and Responsibilities
A clinical monitoring plan is a carefully crafted template for each unique clinical study to guide the participant and clinical care team through the clinical trial process. The PI or Principal Investigator typically oversees the clinical trial process; sometimes, an ISM or Independent Safety Monitor or Data Safety and Monitoring Board or DSMB are added to the team to help provide additional monitoring. [1]
Compliance mishaps can delay or halt the clinical trial process. Unfortunately, non-compliance can be quite costly for the clinical trial sponsor. Non-compliance can cause delays or may result in a financial penalty. Consequently, the PI works with the entire clinical trial team to mitigate the risk of non-compliance issues during the planning stage. The specific roles and responsibilities of the clinical team tend to depend on the type, duration, and size of the clinical study. However, each role articulates a broad description of duties and expectations. [2]
PI: Principal Investigator
The PI governs the entire scope of the clinical trial’s conduct with responsibilities encompassing the study type and design, safety considerations, monitoring, reporting, and any collaborative care needs. The PI is responsible for recruiting trial participants, carrying out the protocol, managing the investigational product, working with the Institutional Review Board (IRB)/Independent Ethics Committee (IEC), gaining informed consent from trial participants, maintaining study records, and overseeing study staff. Consequently, the PI works towards participant safety and the integrity of study data. [2]
The PI serves as an informational gateway between the IRB, the clinical sponsor, the clinical trial team members, hospitals, clinics, and the research participants. The PI relies upon their team members to demonstrate precision in collecting and reporting clinical trial data.
CRA: Clinical Research Associate vs. CRC: Clinical Research Coordinator
A clinical research associate (CRA) and clinical research coordinator (CRC) are distinctive roles. Initially, they work for different organizations. The CRA is employed by the sponsor or the sponsor’s delegated Contract Research Organization (CRO), while the CRC is part of the clinical site.
The CRA is delegated monitoring role duties by the sponsor. CRA responsibilities can span multiple clinical site settings in charge of hosting large numbers of participants for the same trial. The CRA visits the study sites regularly and is responsible for reviewing the necessary clinical reporting documentation and ensuring compliance with the protocol and sponsor standard operating procedures (SOPs). Additionally, the CRA is responsible for ensuring the ethical and regulatory components related to the trial. [4]
The CRC acts as an extended arm of the PI and assists in the responsibilities for one or more specific clinical trials. The PI delegates tasks in writing to qualified and experienced CRCs. The CRC demonstrates the ability to facilitate subject recruitment, review eligibility requirements, design and coordinate subject visits, and perform other duties needed to drive the clinical trial forward.
Their responsibilities tie in closely with those of a CRA, as CRCs are responsible for collecting and maintaining clinical documentation, and CRAs will review and query such documentation to ensure data integrity and compliance.
Study Physicians
A clinical trial may also include a clinical trial physician, or the principal investigator may also serve this role. A clinical trial physician has two primary duties. The first of which is to oversee any medical needs of the participant. The second is to communicate all facets of the participant experience related to the trial intervention to the sponsor. The physician’s perspective is critical to the clinical trial process because the data they collect contributes to the overall safety profile of the study therapeutic.
The clinical study physician is obligated to report any medical details and decisions that correspond to the participant’s condition during the entire lifecycle of the clinical trial. Some of the data collected and reported by the physicians may include the following:
- Adverse effects and potential treatment considerations
- Generalized participant information
- Medical history
- Genetic profiles
- Pre-existing conditions
- Familial medical history
- Lifestyle factors, i.e., drug or alcohol consumption
- Laboratory results and/or imaging
- A comprehensive health profile concurrent with treatment results
Study Nurses
Research study nurses are essential to the clinical trial process. They help to identify risk areas in the therapeutic pipeline. Study nurses administer the investigational product or medical intervention to the participants participating in the trial. Study nurses have an opportunistic vantage point with participants, acting as valuable first responders during critical adverse events. They also tend to gain participants’ trust more easily, helping eliminate potential communication gaps that may arise during a trial.
Study Pharmacists
The study pharmacist is responsible for the medication arm of the clinical study. As the clinical trial team sifts through the process of establishing the safety profile of the chosen study therapeutic, the pharmacist can objectively help pinpoint any potential drug interactions. Study pharmacists also have a pivotal role in helping to define optimal dosing regimens during the scope of the study.
Regulatory Considerations: The Role of the IRB
The Institutional Review Board (IRB) is the body in charge of protecting the rights of clinical trial research participants by reviewing and approving research studies. The IRB is responsible for staying in alignment with the entirety of any FDA-issued guidance. This translates to a blanketing effect within the clinical trial process, ensuring the highest-level ethical and safety standards. [4,5]
Designed to ensure adherence to these ethical standards, the IRB represents a series of regulation-based pillars that serve as a clinical trial check and balance system. [4,5,6]
The IRB areas of focus are primarily participant-centric, meaning they are tasked with rigorously protecting human rights and the integrity of the research process. This is achieved through many routine comprehensive reviews of information provided by the principal investigator, which includes (as applicable) [4,5,6]:
- Research protocols and methodologies
- Recruitment profiles
- Informed consent documentation
- Investigator brochures
- GCP adherence practices
- Clinical site plan
Compliance Considerations: What You Need to Know
Knowledge of the Investigational New Drug/New Drug Application Approval and Commercialization Process
Compliance begins with a detailed awareness of what needs to happen along the Investigational New Drug (IND)/New Drug Application (NDA). This translates to continuous training efforts and enhanced communication standards for every clinical team member. Consequently, every clinical team member involved in the study process must be committed to upholding the outlined principles highlighted within the ICH GCP guidelines. [4]
Clinical Plan Development and Execution
The best way to head off compliance issues is to implement a robust clinical trial plan and risk-based data and safety monitoring plan and pair it with a set of proven SOPs (standard operating procedures). The clinical trial execution typically falls under the umbrella of the PI role, as they are the responsible party for conducting the research at the site. Sponsors are responsible for clinical planning, which entails a full clinical site assessment and review. [1]
Cultivate Trusting Relationships
The CRC role typically has more participant interactions than any other role on the team. The CRC sees participants at routine study visits and engages with participants throughout the entire process. The dynamic strengthens communication, which helps establish participant adherence to the clinical trial protocol. [3]
Clinical Trial Safety Reporting: How to Handle Serious Adverse Events in a Clinical Trial
The PI Must Report the Serious Adverse Events (SAEs) in Real-Time
Delays in reporting SAEs represent a large percentage of compliance errors. The principal investigator must report the details of the SAE to the clinical trial sponsor within 24 hours of receiving notification of the SAE. The critical element here is understanding the vast potential for disruption in the communication chain. [3,5]
Characterization Training
Characterization training involves understanding how events are classified within the report, such as the distinction between a serious adverse event and a serious adverse reaction. The report calls for specific characterizations regarding the nature of the SAE, such as the severity, expectedness, and relatedness to the study protocol intervention. [3,5]
Safety Reporting Requirements
There a several reporting checkpoints that require a timely response by the PI. The challenge is identifying and executing the appropriate next-action requirements after learning about an adverse reaction or event. See below for a quick reference [5]:
Summary
Because the regulatory requirements change and get updated often, running a successful and compliant clinical trial requires continuous education. The success of a clinical study is reflective of clinical team preparedness, communication, and protocol adherence. Identifying avenues to strengthen your clinical monitoring role may require gaining in-depth knowledge of regulatory protocols and the tools that help facilitate the processes involved in the regulatory framework.
References
- https://www.nimh.nih.gov/funding/clinical-research/data-and-safety-monitoring-plan-writing-guidance#:~:text=All%20clinical%20trials%20will%20be,Governing%20Monitoring%20of%20Clinical%20Trials)
- https://research.wustl.edu/about/roles-responsibilities/principal-investigator/
- https://pubmed.ncbi.nlm.nih.gov/21350728/
- https://www.fda.gov/science-research/clinical-trials-and-human-subject-protection/regulations-good-clinical-practice-and-clinical-trials
- https://www.fda.gov/drugs/investigational-new-drug-ind-application/ind-application-reporting-safety-reports
- https://www.fda.gov/about-fda/center-drug-evaluation-and-research-cder/institutional-review-boards-irbs-and-protection-human-subjects-clinical-trials#:~:text=The%20purpose%20of%20IRB%20review,as%20subjects%20in%20the%20research.
