The Food and Drug Administration (FDA) needs to step up the pace on modernising the regulatory framework for clinical trials in the US, says the Washington-based Association of Clinical Research Organizations (ACRO).  

One move in the right direction, the association believes, would be to appoint a Chief Innovation Officer at the FDA with broad authority to approve novel approaches to clinical trials.

There has been some progress in “developing basic building blocks” to steer medical products more quickly, effectively and economically from discovery through to launch, acknowledged ACRO executive director Doug Peddicord in testimony to a recent public hearing.

These advances include the multi-stakeholder Critical Path initiative and other public-private efforts such as the Clinical Data Interchange Standards Consortium, the Clinical Trials Transformation Initiative and the National Institutes for Health Biomarkers Consortium.

Actual product development, though, “remains costly, slow and unproductive”, Peddicord told the FDA hearing in Washington on ‘Modernizing the Regulation of Clinical Trials and Approaches to Good Clinical Practice’.    

Translational research challenge   

In terms of the Critical Path initiative, the next challenge is to transition from basic research and tool development to translational research, he suggested.

Industry should be able to look to the Clinical Trials Transformation Initiative (CTTI) for direction here, but “in our view CTTI has yet to consider undertaking any project that might qualify as ‘transformative’”, Peddicord commented.  

“Instead, its approach is one of doing ‘research on research’ which may well produce white papers and other publications, recommendations, meetings and educational initiatives but is unlikely, we believe, to facilitate any significant change to current practices, let alone transformation of the enterprise.”

In ACRO’s opinion, the focus of the CTTI collaboration should be on innovation and “generating data that would support innovation”.  

What is needed, the association believes, are studies that compare current and innovative approaches to clinical development, as well as pilot or demonstration projects agreed by the FDA (and other regulators, if necessary) and with the potential to “demonstrate actual savings in development time and/or cost for a given product”.    

Among ACRO’s suggested topics for comparison studies or in vivo demonstration projects are:

•    Incorporating more modern regulatory science into clinical study design so that sponsors can generate the data necessary for product approval with fewer trial subjects.

•    Simplifying the informed consent process so that the information provided to potential participants is more intelligible and meaningful.

•    Testing, across therapeutic areas, the use of a single, central Institutional Review Board (IRB) to improve the quality of independent review, make operational practices more consistent and accelerate trial initiation.

•    Approaches to risk-based oversight of sites/investigators by trial sponsors, including statistical/other sampling and remote/other technology-enabled monitoring.

•    Expanding regulatory cooperation and information-sharing for multi-regional clinical trials to limit or eliminate duplicative audits, examinations and reviews.

ACRO also argues that the Critical Path Initiative “should not be yoked to any political agenda, like ‘saving’ the current U.S. research enterprises”, Peddicord noted.

Rather, its goal should be to facilitate a new model that can generate more medical products in less time at less cost. The initiative should be “focused on the needs of patients, not companies, regulators, academic institutions, CROs [contract research organisations], IRBs, or anyone else”.

Industry reluctance

Since there is no formalised process for bringing proposals for innovative drug development projects to the FDA, nor any possibility of securing enforceable agreements with the agency for the approval, execution, oversight and evaluation of experimental approaches, industry “has remained reluctant to pursue innovative approaches based only on the informal assurances offered by FDA officials”, Peddicord told the hearing.

“In effect, the devil we know may be unnecessarily expensive and time-consuming, but the devil we don’t know could be even worse; a cancelled trial, a rejected product application, etc,” he added.

Two actions would help to re-focus the Critical Path initiative, ACRO believes:

•    Engaging a consulting firm or other third party to review and prepare a report for the agency on how the FDA can more aggressively support innovation by the industry it regulates and embrace scientific/regulatory innovation in-house.             

•    Appointing, or seeking Congressional approval to appoint, a Chief Innovation Officer at the FDA who would be responsible for overseeing the Critical Path initiative and would:                                               

-    identify promising new scientific and regulatory approaches to ensuring the rapid development, testing and review of new drugs and devices;                        

-    solicit from industry and other stakeholders proposals for innovative approaches to biomedical product development in the form of demonstration and pilot projects;

-    approve research projects to test and/or compare current and innovative approaches to clinical trials;

-    permit temporary trial-specific amendments to FDA regulations and requirements;

-    facilitate any other initiatives with potential to reduce the cost or time required to develop and test new biomedical products;

-    identify personnel and processes whereby industry and other stakeholders could pursue initiatives such as those mentioned above under formal agreements with the FDA;

-    provide the FDA Commissioner and Congress with an annual report on “specific, quantifiable progress” towards the objectives of the Critical Path Initiative – “a faster, less costly, more productive biomedical product development paradigm”.

“We have reached a stage where bold action, leadership and accountability are required to move the drug development enterprise forward so in the end we all may benefit from new therapies and treatments,” Peddicord concluded.