FDA “A Risk-Based Approach to Monitoring of Clinical Investigations Questions and Answers Guidance for Industry” Clinical Insight Paper

Apr 13, 2023 | News |

FDA “A Risk-Based Approach to Monitoring of Clinical Investigations Questions and Answers Guidance for Industry” Clinical Insight PaperIntroducing the game-changer in clinical investigations: The FDA has just released their highly anticipated guidance document on A Risk-Based Approach to Monitoring of Clinical Investigations Questions and Answers Guidance for Industry in April 2023. This groundbreaking document provides a wealth of information on risk-based approaches to monitoring clinical investigations of human drug and biological products, medical devices, and combination products [1]. It is intended to help sponsors develop monitoring plans that focus on identifying and mitigating risks to data quality and human subject protection.  It offers a comprehensive approach to risk-based monitoring that can improve the quality of clinical trials, reduce monitoring burden, and enhance patient safety [1]. This guidance document provides clear guidance for the implementation of risk-based monitoring of clinical investigations, including a framework for the development of risk-based monitoring plans and outlining the roles and responsibilities of sponsors, investigators, and IRBs [1].

The guidance emphasizes the importance of planning a monitoring approach, developing the content of a monitoring plan, and addressing and communicating monitoring results. It offers recommendations on how to design efficient clinical trial protocols, tools for identifying and tracking potential risks, and procedures for data collection and processing  [1]. The FDA has revised the draft guidance issued in March 2019 and expanded on their August 2013 guidance for industry entitled “Oversight of Clinical Investigations – A Risk-Based Approach to Monitoring,” providing additional information to facilitate sponsors’ implementation of risk-based monitoring. This newest guidance document is organized in a question-and-answer format, which makes it easy to understand and navigate. It provides sponsors with a quality control tool for determining whether investigation activities are being carried out as planned [1].

The FDA recognizes that the traditional approach to monitoring is time-consuming, costly, and inefficient. With this new guidance, sponsors can use innovative technologies and data analytics to identify and address risks in real-time [1]. The guidance encourages sponsors to identify risks early in the clinical investigation and take appropriate corrective actions to mitigate those risks [1]. The FDA recognizes that not all clinical investigations are created equal, and some may require more intensive monitoring than others. The guidance provides a framework for sponsors to assess the level of risk associated with their clinical investigations and develop a monitoring plan that aligns with that risk [1].

One of the key benefits of this guidance document is its risk-based approach, which encourages sponsors to focus on critical data and processes in their monitoring plans rather than using a one-size-fits-all approach. This approach can help sponsors allocate monitoring resources more efficiently and effectively, lessening monitoring load, and improving the quality of clinical trials [1]. Additionally, this risk-based approach can help sponsors identify potential issues earlier in the clinical trial process, enhancing patient safety [1]. Sponsors must identify and assess all potential risks associated with the trial, both before the investigation begins and during its conduct. This includes identifying and monitoring unanticipated risks that may arise during the study. Sponsors are also expected to clearly document any risks, including those that are less likely to occur, and develop a comprehensive monitoring plan that outlines how they will mitigate these risks [1]. A major recommendation of this document is that the monitoring plan should account for overall investigation and site-specific risks. To determine the frequency and intensity of the risk-based monitoring approach, various factors need to be considered [1]. These include the site-specific infrastructure, experience of the Investigator and Sponsor, adequacy of the site staffing, study complexity, quantity and criticality of data collected, and appropriateness of the EDC system (electronic data capture) used to capture metrics [1]. The monitoring plan should be regularly reviewed and revised throughout the trial to ensure that any unanticipated risks are identified and addressed [1].

Sponsors are encouraged to conduct centralized monitoring across all sites to identify inconsistencies, omissions, and ensure consistency and completeness [1]. The guidance also provides recommendations for the use of risk-based monitoring approaches and clarifies the responsibilities of sponsors, investigators, and IRBs in ensuring that clinical trial risks are effectively managed. The FDA emphasizes that sponsors must take a proactive approach to risk management throughout the entire clinical trial process to ensure the safety and well-being of study participants [1].

This guidance document helps sponsors outline the elements that needed to be included in a monitoring plan for clinical trials, with the aim of evaluating risks, communicating monitoring results, and implementing preventive and corrective actions for improvement. A clinical trial monitoring plan should include a description of the monitoring activities, the roles and responsibilities of those involved, and the methods used to detect and assess risks. All monitoring activities, findings and corrections should be documented. The guidance document provides examples of preventive and corrective actions that can be taken in response to monitoring results, such as modifying the protocol or increasing the frequency of monitoring. Overall, the FDA emphasizes the importance of proactively assessing and monitoring all risks, including unanticipated ones, throughout the study conduct.

The release of this guidance is a major milestone for the pharmaceutical and medical device industries, as it provides clear direction on how to develop and implement risk-based monitoring strategies for clinical investigations. Sponsors can now take a more proactive and efficient approach to clinical trials, identifying and addressing risks early in the process (i.e., before beginning an investigation), and also to include unanticipated risks identified during the study; ensuring that data quality and human subject protection are always top priorities [1]. All risks should be monitored during the study conduct, not just those that were anticipated. The FDA also recommends sponsors to conduct ongoing safety evaluations and communicate new safety information in a timely manner to ensure the safety of study participants. The importance of a well-designed and executed safety monitoring plan in the successful conduct of clinical trials is paramount and the FDA expects sponsors to be vigilant in monitoring risks and ensuring the safety of study participants throughout the duration of the clinical trial [1].

This guidance has been eagerly anticipated by the industry for years, and its release marks a significant step forward in the FDA’s mission to protect and promote public health. It provides a framework for sponsors to develop monitoring plans that are tailored to the specific risks of their clinical investigations, ensuring that they are able to identify and mitigate potential problems before they become serious issues and ensure alignment on the risk-based monitoring approach as feasible and effective [1].

Overall, this guidance document is a must-read for anyone involved in clinical investigations of human drug and biological products, medical devices, and combination products. Its recommendations are grounded in decades of experience and research on clinical trial monitoring and provide sponsors with a roadmap for developing effective risk-based monitoring strategies. It stresses the importance of collaboration between sponsors and sites and encourages the use of innovative technologies to monitor investigations in real-time. With the implementation of this document, sponsors, investigators, and IRBs can work together more effectively to ensure the success of clinical investigations. As the industry continues to evolve, this guidance will be an essential tool for ensuring that clinical investigations are conducted safely and effectively, and that the resulting products are of the highest possible quality [1].

Note: The full publication is available for download on the FDA website.


  1. A Risk-Based Approach to Monitoring of Clinical Investigations Questions and Answers Guidance for Industry. April 2023. link: https://www.fda.gov/media/121479/download

Evita Asumugha – Senior Medical Writer