AML Researchers Propose New Risk-Based Model for Monitoring Clinical Trials

Louvain, Belgium: – Researchers from the contract research organization AML Clinical Services bvba (AML) have proposed a re-engineered risk-based methodology for monitoring clinical trials to overcome widely recognised shortcomings in current models. The new model also supports recently proposed guidelines issued by the world’s leading medical research regulatory agencies.

AML’s founder Anne-Mie Lenaers and Senior Clinical Researcher Annelies De Cupere set out their findings in an academic paper ‘Merging the regulatory proposals for risk-based quality management of clinical trials; A more in-depth application to the monitoring of the clinical investigational site’.

The paper was accepted by the Belgium’s Catholic University of Louvain (KUL) following academic review earlier this year, following submission as foundation paper for its one year course “Quality Management in biomedical, biotechnological and pharmaceutical environment”.

The two researchers were inspired by growing awareness that current practices in monitoring clinical trials no longer reflect the purposes of trial monitoring set forth in the 1996 Good Clinical Practice guidelines developed by the International Conference on Harmonisation (ICH). Although these standards do not specify how to conduct monitoring, over time intensive on-site monitoring, focused on detecting errors that had already occurred and reacting to them, became common practice.

Growing limitations
“However, with the growing complexity of trial designs, therapies, and the recent spur in technologies, current practices can no longer guarantee the protection of the human subject and the integrity of trial data,” say the AML researchers.

Several initiatives, including CTTI, ADAMON project and the OPTIMON study have been adopted by stakeholders to identify and compare monitoring activities. In autumn 2011, leading regulatory agencies; the US Food & Drug Administration (FDA), European Medicine Agency (EMA) and the UK’s Medical Research Council (MRC), Medicines and Healthcare Products Regulatory Agency (MHRA) and Department of Health (DH) issued guidelines to encourage sponsors of clinical trials in taking a more risk-based approach towards monitoring.

The purpose of the AML-authored paper is to draw up a risk-based quality management approach for monitoring that meets the expectations of the agencies and is capable of being applied in global settings and to all types of clinical research.

Focus on monitoring
The investigation was based on the agency guidelines, with the proposed model tested against the monitoring aspects of a fictitious investigational site conduct of a prototype clinical trial of fish oil supplements in elderly Alzheimer’s sufferers.

Although the model is not yet validated, the authors say it provides the stakeholders with an idea on how to analyze the trial risks and take informed decisions on the organization of monitoring practices.

“We realize that for most of the stakeholders the implementation of such an approach is new and requires a change in their processes. Initially the assessments will be very time- and resource consuming and will require many revisions due to the learning curve. But once the stakeholders has gained knowledge and experience, they will benefit from this approach though having high quality data and better allocation of resources,” the authors conclude.

Challenges
Challenges identified in the paper include:

• Additional training in contemporary risk management techniques required in the Risk Management Team (RMT).
• Detailed knowledge of the clinical trial, departmental processes and the investigational product/intervention required among RMT members. Incomplete knowledge of any one of these elements might affect the outcome of the risk assessment and create uncertainty.
• In cases where monitoring responsibilities are outsourced to CROs or other third parties, clear and open two-way communication required between sponsor and monitors, with additional responsibilities in the risk management process clearly defined and set out in the service agreement.
• Standard operating procedures (SOPs) must be in line with the risk-based approach.

The paper also identifies further challenges when selecting monitoring practices, especially since there is currently no empirical evidence available about the best monitoring practices to adopt.

“The Clinical Operation team has to apply common sense and rely on their experience when deciding which monitoring practices to implement,” say the authors.

“A risk-based approach is a continuous process and should be repeated during the clinical trial. In clinical trials with multiple and/or high risks, there will be a tendency to re-assess the risks periodically.

“If a clinical trial initially shows low risks (as is usually the case in, for example, observational studies), the sponsor should be aware that risk can change over time and should continue to perform at least periodic review of the Risk Assessment Report (RAR). Although risks might be low, appropriate warning signals and triggers and verification processes should still be implemented,” the paper states.

Lenaers and De Cupere have taken insights gained during the research through to their practice in AML.

“It is our expectation that the implementation of a risk-based model for monitoring enhances the quality and validity of the data and protection of trial subjects. As quality has always been a primary objective of AML, we are continuously looking for ways to improve our services to meet the highest standards. In order to further improve our own monitoring quality at AML, we are currently setting up a Quality Department within the Company. This will be an important step in our aim to secure ISO:9001 certification during 2014,” said Anne-Mie Lenaers.

Contact:
Anne-Mie Lenaers: Director, AML Clinical Services bvba
Annelies De Cupere: Senior Clinical Research Associate, AML Clinical Services bvba
Email: [email protected]
Tel: +32 (0)16 78 21 70

For more information about the risk-based model for monitoring clinical trials, please contact AML Clinical Services directly.