How should sponsors and sites define successful clinical monitoring today, and what can they do to ensure they achieve their goals?
By John Lehmann, Director of Business Development
Whether you’re performing it on-site or remotely, clinical monitoring comes with many challenges. In the past decade (and even the past year), monitoring has evolved.
How should sponsors and sites define successful monitoring today, and what can they do to ensure they achieve their goals? Here’s a closer look at what monitoring should accomplish and how to improve outcomes.
What Is Clinical Monitoring?
The FDA defines monitoring as the act of overseeing an investigation. The International Organization for Standardization elaborates further, explaining that the purpose is to ensure an investigation is “conducted, recorded, and reported in accordance with the clinical investigational plan (CIP), written procedures, the International Standard, and the applicable regulatory requirements.” (ISO 14155:2011(E) 3.29; ICH E6 1.38).
To break it down further, the primary goals of monitoring include:
- Protecting the rights and wellbeing of study subjects
- Ensuring data integrity
- Ensuring the trial is conducted according to established plans and regulations
- Identifying areas of non-compliance
- Promoting high standards of quality
- Identifying research misconduct or fraud
These are significant responsibilities, and they shouldn’t rest solely on one person. Clinical monitoring is a mindset everyone involved in research should adopt.
3 Steps To Improve Your Clinical Monitoring Efforts
1. Identify Quality Monitors
Clinical research associates (CRAs) or field monitors are the most well-known type of monitor. They may conduct site assessment visits, site initiation or training visits, interim monitoring visits, and/or close-out visits.
Although FDA regulations state that monitors should be qualified by training and experience, it does not specify any standard qualifications. Monitors often come from a variety of medical and scientific backgrounds, and many adopt their own processes and procedures.
Fortunately, the Code of Federal Regulations (21 CFR 812.43(d) offers guidance on what qualities to look for:
- Regulatory knowledge
- Clinical/scientific knowledge
- Knowledge of the investigational plan
- Knowledge of the device being studied
- Knowledge of sponsor procedures
It’s important to document these qualifications and training. As we often say, if it wasn’t documented, it wasn’t done!
2. Develop A Monitoring Plan
A well-structured monitoring plan defines the expectations of monitors and helps improve compliance. The idea behind risk-based monitoring is to plan and prioritize monitoring activities based on the risks involved.
Here are a few questions to consider as you develop your plan:
- What type of study is being conducted? (IDE? 510(k)?)
- What are the risks?
- How many sites and subjects will be involved?
- How complex is the study?
- What are the endpoints and measures? Are they quantitative or qualitative?
- How much data is being collected?
- How complex is the study population?
- What is the expected rate of enrollment?
- What is the experience level of the investigational sites(s)?
- Where is the data being used?
Depending on your answers, you may determine you need more or less frequent monitoring visits. You may also decide your study is a good candidate for remote monitoring, on-site monitoring, or a hybrid approach that includes a mix of both.
3. Perform Monitoring Training
Even after you’ve hired well-qualified monitors, enrolling them in a standard clinical research training program ensures they have the foundational knowledge they need to apply the regulations and think critically. It also helps establish consistent processes.
Here are a few of the most important subjects to cover in your training for monitors:
- Ensuring informed consent. Monitors review all informed consent documents, including obtaining electronic informed consent (e-consent.) They need to ensure all subjects gave proper informed consent to participate in the clinical trial and that this was documented correctly.
- Assessing data integrity. Monitors review medical records and compare them to the records submitted to the sponsor. They need to be trained to spot any discrepancies and submit a data query to resolve them. Monitors should also clarify questionable source documentation to ensure the data being submitted accurately reflects the appropriate source and the clinical condition of the study participant.
- Assessing protocol compliance. Failure to comply with study protocol is one of the most frequent violations cited in FDA Warning Letters. This is why it’s imperative that monitors ensure sites adhere to all established protocol. If they notice discrepancies, they should discuss a corrective action plan.
- Reviewing essential documents. Monitors also review essential documentation, including IRB correspondence, sponsor correspondence, lab certifications, CVs, and training records. As they review these documents, they should refer to the FDA Guidance for Industry ICH GCP E6, Sections 8.2-8.4 or the ISO 14155:2011(E) Annex E.
- Assessing overall site capabilities. Monitors periodically tour research sites, including procedure rooms, device storage areas, research documentation storage, and patient follow-up areas. They also interview study personnel and need to know how to spot any areas of concern. For instance, do research coordinators have enough time to complete their tasks? Are they properly trained? Monitors should feel confident making recommendations to sites to enhance any areas that need improvement.
- Assessing device accountability. Monitors conduct investigational product accountability, comparing what was sent from the sponsor to what was used or returned and what is in stock at the site. They should ensure only appropriate study personnel had access to the investigational product and devices were only used in subjects who gave informed consent.
The Benefits Of Hiring A Monitoring CRO
Effective monitoring is vital to protecting patients, ensuring data integrity, and ultimately obtaining approval for your device. Hiring quality monitors, training them, and holding them accountable to hold your sites accountable takes time and effort, but it’s essential if you want your study to succeed.
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