Risk assessment is a critical process in clinical trials that involves thorough and systematic evaluation of potential risks to the study volunteers, biases affecting the results and data integrity/protection. The process requires the use of risk assessment forms to identify, evaluate, and mitigate risks and ensure patient safety and data integrity.[1] The scope of this article is to discuss whether the utilization of clinical trial assessment templates is worth the time of the study sponsors/investigators.
As per ICH guidelines and GCP, all study sponsors and investigators of the clinical trials must ensure that the trials are designed, conducted and monitored rigorously to minimize or eliminate risks. This is to ensure that the safety of the study volunteers is protected, generating reliable and scientifically robust data and uncompromised data integrity. These mandates are applicable for sponsor-funded clinical trials (CROs) and academicians-led clinical trials.
In clinical trials, the risks are predominantly classified into two categories such as:
Risks to the patient’s safety and rights (violation of informed consent form)
Events risking the successful outcomes of the trial study such as inadequate patient recruitment, less significant (clinical/statistical) data poor funding etc
The risk assessment tool is a template guide for study investigators/sponsors that helps the end users identify and address the potential risks of a clinical trial by good clinical practice (GCP) mandates. The clinical trial assessment templates assess the likelihood and impact of various biases and risks affecting the quality and outcomes of the clinical trial study. Establishing a quality-based management system is useful to identify and overcome the quality-related risks of the clinical trial. To be user-friendly, it is very important to frame step-by-step guides, assessment forms and a risk assessment tool that identifies and mitigates/reduces the risks of the clinical trials is worth exploring and utilizing to improve clinical trial outcomes.
The study sponsors and investigators can create a risk assessment template to check the risks and hazards at the levels of protocol, protocol site, clinical program and clinical region.[2]
Check your trial design
Some of the main reasons to employ risk assessment tools are:
A. Improved data integrity:
By mitigating the risks associated with data compilation and management to ensure the reliability of the study.
B. Better patient safety:
Continuous risk assessment can help the study sponsors and investigators to effectively identify and address potential risks even before impacting the patients.
C. Improved study efficiency:
Identifying the risks and devising management plans specifically for the identified risks can help the trial processes by reducing delays and unexpected study delays.
D. Enhanced regulatory compliance and reduced overall study costs:
Regular monitoring of the study and risk assessment could improve GCP compliance and other regulatory processes. These proactive approaches could address all hazards and risks and prevent overall expenses, delays and study termination.
Some of the essentials of a risk assessment template are:
1. Identification of potential/possible risks of clinical trial design (biases, flaws etc)
This is the first step of the clinical trial assessment tool that involves analyzing the potential/possible risks of the trial design, data integrity and study volunteers’ safety and listing the same for further analyses [3].
Risk, by definition, is the possibility that impedes or harm might happen upon exposure to a hazard. The risk is a continuous factor and quantifying the risk based on the severity as low, medium and high is useful to focus and mitigate the risk as per severity. The reduction and elimination of such high-risk factors is a critical step. To quantify the risk, it is important to predict the likelihood of the hazard, harm and its impact on the study with quantification (determination).[4]
2. Analyzing the listed risks:
This step involves the assessment of the likelihood and severity of identified risks by effectively employing any of the effective evaluating techniques including the risk matrix. Identifying the potential hazards in the trial is the key initial step followed by an assessment of the likelihood of hazard occurrence and the severity of the impact in case of occurrence of impact. These key steps are followed by assessing the risk in the next step based on the severity by determining and multiplying.[5]
3. Evaluating the risks severity:
Upon analyzing the risks, the next key step is to determine the overall risk level and list the severity as low to high based on the analysis to prioritize the high risks over low risks for mitigation.
These steps are then followed by efforts to manage the observed risk and must be prioritized. Some of the points from where risks may occur are critical processes and data points. Focusing on these chicken necks is known as risk-based management and must be considered as high risk or critical risks to manage in priority over medium risk and low risk.
One of the key steps of risk assessment for a clinical trial is to select the right risk assessment tool relevant to the clinical trial. This approach will ensure uniformity in the due process.
Once the right template is selected, a list of parameters will be presented in the to-do list as an attributes list. These are basically FAQs to evaluate the risk of adverse events or the data integrity. The to-check attributes can be checked by entering the appropriate values and the attributes can be deleted or added, as needed.
Upon assessing the risks and hazards, the study sponsors should implement effective management plans to overcome the risks throughout all the stages of the clinical trial. The prime focus must be study participants’ rights protection and data integrity.
These strategies must be written in parallel with the development of trial protocol/design which must be reviewed and agreed by all stakeholders.
4. Mitigation of identified risks:
This step involves the development and implementation of risk mitigation strategies to overcome the identified risks such as clinical trial protocols, trial designs or procedures and training to aid further monitoring.
To overcome the risks, it is best to decide on the response to effectively manage and monitor each risk (and hazard as well). Some of the responses to the risk include avoiding or eliminating the risk by amending the protocol or terminate the study before it is too late with financial implications. Then mitigate the risks by adjusting without eliminating the risks. These mitigations may either reduce the likelihood of occurrence or reduce the impact of the negative risk. The mitigation process also aids the sponsors and investigators for site transfer to CROs with specific expertise. In a few cases, the risks are typically accepted and the impacts are cushioned by mitigating approaches.
The risk assessment template must be broadly divided into three main parts including:
Categorization of risk of the intervention, compared to standard of care procedure/product already in the market.
Assessment of other risks and hazards such as procedures, study population and trial design to identify the vulnerabilities and ways to mitigate the risks.
Outcomes of the hazards and risk assessment and its implications in the outcomes. It is very important to outline the identified risks and ways to overcome these problems alongside the trial protocol in the study monitoring plan and continuous monitoring through the study must be ensured.
Some of the effective risk mitigation strategies include:
1. Ensuring effective protocol design:
It is very important to include an effective study protocol with vetted inclusion and exclusion criteria, data collection and safety monitoring to reduce or eliminate the risks.
2. Imparting training to the study investigators:
Providing adequate training to the study investigators and coordinators on clinical trial design and protocol, GCP guidelines and risk mitigation strategies might improve the outcomes.
3. Rigorous monitoring and signal detection:
Ensuring rigorous monitoring and trial oversight processes must be ensured for timely real-time detection and mitigation of risks. These approaches need independent data safety monitoring committees, periodic site visits etc.
4. Assuring study volunteers safety:
Pro-active implementation of preventive measures to protect the safety and well-being of the study volunteers by implementing rigorous safety monitoring protocols, standby teams for emergency response and also by providing informed consent to the study volunteers. These mitigation strategies could effectively improve patient recruitment, and reduce study costs and attrition.
5. Implementing data management paired with AI:
To improve data accuracy, integrity, reliability, and validity, it is very important to implement an AI-supported robust data management system.
6. Safety monitoring and timely reporting:
Framing and implementing procedures to early reporting of detected safety signals and unbiased assessment of adverse events, protocol deviations and subsequent corrections/amendments are important for effective risk mitigation.
7. Sticking with regulatory compliance:
Ensuring strict compliance with regulatory agencies and clinical trial guidelines can eliminate regulatory hurdles and delays.
8. Periodical and continuous monitoring:
Continuous monitoring of the effectiveness of risk mitigation strategies throughout the study and adapting mitigation strategies as needed could effectively run the study without impeding risks. The continuous monitoring must include periodical reviews and subsequent meetings, interim data analysis and communication with the stakeholders.
9. Documentation of results and regulatory reporting:
Documenting all risk management protocols, assessments and implementation in the clinical trial study brochures and clinical study reports for regulatory submissions is very important for AdComm and stakeholders meetings.
10. Developing a risk management plan:
Developing a risk management plan with explanations or risk monitoring plans, how to communicate the identified risks, and further escalations with subsequent contingency plans.
11. Monitoring the risks to ensure effective mitigation:
The risk monitoring step involves continuous monitoring of the effectiveness of mitigation strategies and also to adjust the plans according to the trial design amendment.
As the risks greatly vary between the trials, the clinical trial assessment tool should provide several examples for further guidance to implement in all clinical trials. The risk assessment tool covers the risks arising from the system level and the clinical trial level. The clinical trial assessment template is generally useful for clinical trials in CRO and academic settings.
The risk assessment templates currently available in the market are
Clinical trials toolkit, which provides templates and tools for various aspects of clinical trials including risk assessment [6].
Sctoplatforms, a step-by-step, user-friendly risk assessment tool for clinical trials. [7].
Global health trials, a clinical trial risk assessment template with various tools for risk assessment.[8]
https://docs.oracle.com/cd/E88140_01/books/CTMS/ctmsclinicalprog014.htm
http://www.bath.ac.uk/hr/stayingsafewell/hazard-risk-management/index.html
https://clinicaltrialshub.htq.org.au/blog/how-to-conduct-a-clinical-trial-risk-assessment/
https://www.sctoplatforms.ch/en/tools/risk-assessment-form-for-clinical-research-projects-30.html
Thomas Wood has recently joined the Clinical Trial Files podcast with Karin Avila and Taymeyah Al-Toubah, discussing the inception of the Clinical Trial Risk Tool, what impact AI can make in clinical trials, and what Alan Turing would make of it all. This is an episode dedicated to Alan Turing’s 113th birthday on 23 June 2025. You can find the episode on Spotify Apple Podcasts Amazon Music Podcast Index Fountain Podcast Addict Podverse.
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