Clinical Monitoring Objectives
Clinical trial management mandates procedural accuracy, careful planning, and coordinated execution. Sponsors and their monitors assess clinical studies to ensure alignment with compliance and regulatory protocols. The assigned site monitor is tasked with the priority of preserving patient rights and ensuring their safety. 
The principal investigator (PI) is also responsible for collecting clinical trial data and mitigating any risk factors that may jeopardize compliance, ethics, or safety standards. Each clinical study undergoes a detailed site assessment to determine the specific needs and purposeful measures to help ensure the study proceeds well from start to finish. The level of complexity associated with the clinical trial protocol usually determines the type of clinical study site that will work best. 
Clinical Monitoring Types
ICH E6(R2) requires sponsors to develop specific monitoring plans for each protocol, considering the risk level of the study, among other factors critical to quality. The monitoring plan should specify the monitoring that will be used and the justifications for those decisions.  Sponsors can utilize on-site monitoring, centralized monitoring, or a hybrid approach incorporating both types of monitoring to fulfill their regulatory monitoring responsibilities.
On-site monitoring represents a common clinical trial monitoring method used by the pharmaceutical industry. On-site monitoring entails performing routine risk assessments and in-person site visits at specified time intervals to help ensure subject safety and data integrity. With the acceptance and encouragement from regulators, we have seen remote and centralized monitoring increase in popularity over on-site monitoring.  However, there are many instances where on-site monitoring is the best option. This is especially true in adverse effects reporting or locations where internet reliability is challenging. 
Centralized monitoring is a one-location hub type of monitoring activity with a specialized central monitoring team overseeing the process. The FDA states that it consists of “a remote evaluation carried out by sponsor personnel or representatives (e.g., clinical monitors, data management personnel, or statisticians) at a location other than the sites at which the clinical investigation is being conducted.” 
Centralized monitoring may be a helpful tool to reduce the costs of on-site monitoring visits, but sponsors may have to budget for increased costs on programming and analysis.  In addition, it may allow sponsors to target on-site monitoring for higher-risk clinical studies and help identify areas in the protocol for potential clarification. 
Independent survey statistics reveal that 70% of patient participants reside two hours from their clinical trial sites. 
Decentralized clinical trials allow subjects to join a clinical trial who may otherwise not be logistically able to participate.  These virtual trials can also recruit, provide study medication, and collect data from subjects entirely remotely via internet interactions, all while securing and maintaining the data virtually. . Akin to remote monitoring, decentralized monitoring offers a virtual clinical monitoring experience made possible by telemedicine practitioners and electronic data capture technology (also called EDC). 
ICH E6(R2) states that the sponsor of a clinical trial “should develop a systematic, prioritized, risk-based approach to monitoring clinical trials.”  According to the FDA, a risk-based approach focuses “oversight activities on preventing or mitigating important and likely risks to investigation quality, including risks to human subject protection and data integrity.” 
Holistic in nature with aims at optimizing overall study quality, a snapshot of risk-based monitoring emphasizes the following elements :
- The identification of key risk indicators (KRIs)
- Reduced source document verifications (SDVs)
- Centralized and remote monitoring (hybrid monitoring)
- Reduced source document review (SDR)
- Streamlining costs
- Time conservation
- Enhanced safety measures
- Utilization of third-party clinical contract organizations
Remote monitoring is also considered a virtual monitoring methodology. Technology facilitates remote monitoring capabilities by reviewing clinical trial data remotely through EDC systems, eliminating the need for on-site data collection and review.  Remote monitoring is growing as a more attractive methodology for certain trial types, mainly because of the recent COVID-19 pandemic, which limited the sponsor’s ability to go on-site for monitoring.
The pandemic provided monitoring teams an opportunity to see what is possible in terms of a remote monitoring environment. Because of the lightning-fast learning curve that investigators were forced to work under, many of the obstacles previously associated with remote monitoring became readily identifiable and offered real-time solutions. As a result, investigators are now gifted with the opportunity to analyze relevant case examples with many lessons to draw from. 
Sponsors may use different types of monitoring to best fulfill their regulatory responsibilities. Every kind of monitoring has benefits as well as considerations. Regulators encourage sponsors to integrate quality into risk management plans and develop trial-specific monitoring plans for each study. Monitoring plans should include a justification for the type and frequency of monitoring.
- Farrell, Barbara, Sara Kenyon, and Haleema Shakur. 2010. “Managing clinical trials.” Trials 11(78). https://doi.org/10.1186/1745-6215-11-78. Accessed November 14, 2022
- Patchev, Stephanie. 2017. “Why the value of on-site monitoring cannot be challenged by remote/ centralized monitoring.” EU, November 29. www.clinfo.eu/on-site-monitoring/. Accessed November 11, 2022.
- Malia, Joanne. 2019. “The Value of Centralized Monitoring.” SOCRA Blog, November 19. Accessed November 10, 2022. https://www.socra.org/blog/the-value-of-centralized-monitoring/#:~:text=The%20FDA%20definition%20of%20centralized,clinical%20investigation%20is%20being%20conducted.%E2%80%9D.
- Van Norman, Gail A. 2021. “Decentralized Clinical Trials: The Future of Medical Product Development.” JACC: Basic to Translational Science 6(4):384-7. https://www.jacc.org/doi/epdf/10.1016/j.jacbts.2021.01.011. Accessed November 14, 2022.
- Barnes, Brian, Nicole Stansbury, Debby Brown, Lauren Garson, Geoff Gerard, Nickolas Piccoli, Debra Jendrasek, Nick May, Vanesa Castillo, Anina Adelfio, Nycole Ramirez, Andrea McSweeney, Ruth Berlien, and Paula Jo Butler. 2021. “Risk-Based Monitoring in Clinical Trials: Past, Present, and Future.” Therapeutic Innovation & Regulatory Science 55(4):899-906.
- 2019. “Decentralized clinical trials: Are we ready to make the leap?” Biopharma Dive, January 29. Accessed November 10, 2022. https://www.biopharmadive.com/spons/decentralized-clinical-trials-are-we-ready-to-make-the-leap/546591/.
- Varma, Niraj, and Renato Pietro Ricci. 2015. “Impact of Remote Monitoring on Clinical Outcomes.” Journal of Cardiovascular Electrophysiology 26(12):1388-95. https://onlinelibrary.wiley.com/doi/abs/10.1111/jce.12829. Accessed November 14, 2022.
- Annis, Tucker, Susan Pleasants, Gretchen Hultman, Elizabeth Lindemann, Joshua A. Thompson, Stephanie Billecke, Sameer Badlani, and Genevieve B. Melton. 2020. “Rapid implementation of a COVID-19 remote patient monitoring program.” Journal of the American Medical Informatics Association 27(8):1326-30. https://academic.oup.com/jamia/article/27/8/1326/5835871. Accessed November 14, 2022.
- S. Food and Drug Administration (FDA). 2013. “Oversight of Clinical Investigations – A Risk-Based Approach to Monitoring.” Accessed November 14, 2022.
- International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Pharmaceuticals for Human Use (ICH). 2016. “ICH Harmonised Guideline – Integrated Addendum to ICH E6(R1): Guideline for Good Clinical Practice E6(R2).” Accessed November 14, 2022.
- S. Food and Drug Administration (FDA). 2019. “A Risk-Based Approach to Monitoring of Clinical Investigations: Questions and Answers; Draft Guidance.” Accessed November 14, 2022.