Recognising the “dramatic changes” in the global environment for clinical trials over the last 25 years or so, the US Food and Drug Administration has scheduled a public hearing next month to gather views on whether and how it can do more to modernise and streamline its approach to regulation and Good Clinical Practice (GCP) in the field.
Representatives of clinical trial sponsors, contract research organisations (CROs), clinical investigators, academic institutions, institutional review boards (IRBs), professional societies, trade bodies, patient and consumer groups, and other interested parties are invited to the hearing at the FDA’s White Oak Campus ion Maryland on 23-24 April 2012.
The agency says it is “aware of concerns” within the clinical trial community that “certain regulations and policies applicable to the conduct of clinical trials may result in inefficiencies or increased cost and may not facilitate the use of innovative methods and technological advances to improve clinical trial quality”.
The FDA is already engaged in trying to modernise the regulatory framework for clinical trials and GCP approaches, it notes.
The purpose of the hearing is to “solicit public input from a broad group of stakeholders on the scope and direction of this effort, including encouraging the use of innovative models that may enhance the effectiveness and efficiency of the clinical trial enterprise”, the agency explains in a Federal Register notice.
How it’s changed
Among the ways in which the clinical trial environment has altered drastically since the relevant US regulations were introduced over 25 years ago, the FDA cites the increased size and complexity of clinical studies, higher volumes of trials conducted globally, greater use of CROs and the participation of vulnerable populations, as well as “numerous” scientific and technological advances.
Accordingly, the agency is reviewing its regulatory strategy for clinical-trial oversight to “ensure that it meets the regulatory objectives of ensuring human subject protection and the quality and integrity of data supporting regulatory decision-making, without being unnecessarily burdensome or unduly impeding implementation of innovative approaches”.
The FDA refers to a number of steps it has already taken to improve and modernise its regulations, policies and practices in this area. They include:
• The Critical Path Initiative (CPI), introduced in 2004, and within that framework:
- The Human Subject Protection and Bioresearch Monitoring Initiative (2006)
- The Clinical Trials Transformation Initiative (CTTI) set up as a public-private partnership with Duke University (2007).
Over the past few years, the agency has also issued a several regulations and guidance documents addressing the conduct of clinical trials.
The collaborative effort with CTTI also identified Quality Risk Management (QRM) principles and Quality by Design (QbD) as “models that, with adaptations, could contribute to improved data quality and integrity in clinical trials”, the FDA notes.
QRM is a systematic process for identifying, assessing, controlling, communicating and reviewing the risks associated with a particular activity or mechanism.
QbD is a risk-based, quality approach used successfully in manufacturing. It emphasises building quality into processes from the very beginning.
Applied to clinical trials, the FDA suggests, QbD “would prospectively define factors most critical to trial quality and data integrity (e.g., proper randomisation, effective blinding to ensure unbiased ascertainment and analysis of study outcomes) and prospectively identify risks critical to those factors”.
The trial sponsor would then design the protocol, oversight and monitoring mechanisms, as well as data management, archiving, and analysis processes, to eliminate or mitigate these identified risks.
In addition to these initiatives, the FDA has sought to improve its clinical trial inspection processes and to co-ordinate these processes worldwide, it points out.
The agency is also involved in a Good Clinical Practice Initiative with the European Medicines Agency, in which the FDA and the EMA share information on clinical trial applications, collaborate on joint and observational inspections, participate in bilateral training, and keep each other informed about GCP-related legislation, regulatory guidance and related documents.
Not efficient enough
Nonetheless, the agency has learnt from various forums that certain of its regulations and compliance practices “may result in inefficiencies or may not facilitate the use of innovative methods to improve clinical trial quality or the use of technological advances (e.g., use of the Internet to gather data, conduct certain types of research, obtain informed consent)”.
It has also heard from clinical trial sponsors and CROs that these parties are “reluctant to change their processes related to clinical trial oversight and management because of uncertainty about whether new processes would be in compliance with applicable regulations”, the Federal Register notice says.
Among the issues scheduled for discussion at next month’s hearing are:
• What additional efforts the FDA should be making to modernise its GCP regulations, policies and practices, and through which means (e.g., regulations, guidance, pilot projects, strategic alliances).
• What measures the agency could consider to help mitigate some of the challenges arising from increased clinical trial complexity and globalisation.
• How the use of innovative methods, models and technological advances, including QRM principles and QbD, could contribute to data integrity, clinical trial quality and the safety of human subjects, while streamlining the conduct of clinical trials.
• How the agency could encourage adoption of these methods and models.
• What are the specific stakeholder challenges posed by the FDA’s GCP regulations, policies, and/or practices in trying to build quality into the clinical trial process.