Moving Towards a Risk-Based approach to Clinical Trial Management
pharmafile | April 3, 2012 | Feature | Research and Development |
Clinical trials need to be managed to rigorous standards in order to secure the quality and integrity of every aspect of the trial, to ensure the rights, safety and well-being of trial subjects are protected and that the results of the clinical trials are credible.
The case for risk-based strategies
Section 5.1 of ICH GCP, and indeed Article 2 of the GCP Directive 2005/28/EC, require that sponsors implement and maintain systems for quality assurance and quality control. Sponsors may delegate this task, but they still remain responsible for ensuring that such systems are implemented.
Ensuring compliance with relevant regulations, good planning, implementation and review of quality systems are integral components in achieving a good quality clinical trial. However, the cascading nature of the implementation process (sponsors…to CROs…to study sites and back again), is necessarily time and resource-consuming and represents a significant proportion of the cost of drug development.
Current trial management procedures, particularly in relation to quality management, are not always proportionate or appropriate to the context of individual studies and their aims; particularly in respect of academic-based studies. This is mainly because these procedures have developed as a consequence of various environmental, commercial and ideological factors, such as;
- Rising risk averse culture
- Increased globalisation of clinical trials
- Pressures to shorten timelines
- Increases in the regulatory burden (possibly also over-interpretation)
- Increases in the number of parties involved in clinical trials
The subsequent expansion in costs and resource requirements, suggest that the current approach to clinical trial management needs review and reorientation. Primarily by targeting resources to address the most important issues, and especially those associated with identifiable risks to the well being of trial subjects and the quality of trial data.
Regulatory bodies have recognised this and have been proactive in issuing guidance and consultation documents looking at risk-based strategies.
In May 2011, the EMA released a ‘Reflection paper on risk-based quality management in clinical trials’ for general consultation and asking for comments by the end of last month (Feb 2012). In recognizing that quality systems are costly and time-consuming to implement, it suggests that “a scalable and proportionate approach” is required in order to cover the needs of all stake holders from academic researchers right through to multinational pharmaceutical organisations.
The FDA has published draft guidance to industry for a risk-based approach to monitoring (August in 2011). It describes possible strategies for monitoring activities to reflect a modern, risk-based approach to focus on critical study parameters most likely to ensure subject protection and overall study quality. It suggests that a combination of monitoring activities could be used to oversee a study. For example, greater use of centralized monitoring methods, where appropriate, which may still enable sponsors to monitor the clinical study, and ensure the quality and integrity of clinical trial data, as effectively as with routine monitoring visits.
The MHRA, MRC and DH have also issued a draft guidance to facilitate a risk-proportionate approach, whilst applying the principles of GCP within the context of the current EU regulatory requirement. The aims were to draft a process for key stakeholders to assess the level of risk associated with a clinical trial, and to develop risk assessment tools to manage and conduct clinical trials of investigational medicinal products (IMPs) in a risk-proportionate way. Since the guidance resulted from a working group of members from each respective organisation, it is inevitably biased towards academic studies, however their advice can be applied to any study when assessing potential risk factors.
A risk-based approach, to the regulation, management and monitoring of all clinical research, is increasingly being considered as a way to deal with the challenges of time, cost and operational implementation of clinical trials, by proactively identifying, assessing and planning for possible key risk factors. The general process for a risk-based approach can be summarised in four basic steps;
- Identification; Critical review of what might go wrong, probability that it will occur and significance of possible impact on study
- Planning; Grade risks, agree how these risks can be mitigated and identify trigger points for corrective actions
- Implementation; at trigger point, implement agreed actions
- Monitoring; constant review to ensure that trigger points are not missed, actions are effective in mitigating risk and there are no implications for other activities / risks.
With the whole process underpinned by good communication between parties involved.
Summary
There is increasing evidence that a risk-based approach to management of clinical trials is both possible and acceptable to key stakeholders and may provide benefits in terms of effectiveness and efficiency.
Although clinical studies follow similar principles and procedures, each is unique in terms of aim, content, complexity and associated risk factors. Each study is therefore also unique in terms of the potential consequences of risks going unchecked and becoming issues.
The concept of a risk-management approach has seen its early stages of implementation in academic-based studies, and although it is beginning to work its way into the commercial setting, the Pharma industry is, on the whole, still at the stage of evaluating how it can be implemented on a practical and operational basis. There is, however, little doubt that risk-based strategies will develop to encompass all aspects of the clinical trial process.
By: Dr Ignazio Di Giovanna – Owner & Director at CCA (2000) Ltd
Visit www.cca2000.co.uk
