The US National Cancer Institute aims to halve the time it takes to initiate NCI-supported clinical trials through a range of measures including tracking systems and better support for protocol development.

The Institute has already set in motion a number of the initiatives to improve the cancer trial activation process recommended in a report by the Operational Efficiency Working Group (OEWG) of the NCI’s Clinical and Translational Research Advisory Committee (CTAC).

The moves also address concerns raised in a commissioned report by the US Institute of Medicine (IoM) on the NCI’s Clinical Trials Cooperative Group Program, which suggests the system for conducting oncology clinical trials in the US is “approaching a state of crisis”. The IoM report endorsed the OEWG recommendations, which were incorporated as an appendix.

The Cooperative Group Program comprises a network of cancer centres and community oncology practices across the US that develops cancer trials and enrols some 25,000 to 30,000 patients a year into these studies. As the IoM report points out, though, only around 60% of Phase III trials sponsored by the NCI are actually completed, “which is a terrible waste of human and financial resources”.

A major problem, the IoM notes, is “the complex system of designing, reviewing and initiating Cooperative Group clinical trials, which has become a lengthy and redundant process typically requiring years to complete”.

Efforts to optimise the effectiveness and safety of Cooperative Group trials mean proposals are often “redrafted and recycled” by multiple stakeholders from academic institutions, federal agencies, institutional review boards and industry, the IoM says. The system “also lacks an adequate process for prioritising trials and selecting those most likely to be successful”.

New deadlines

According to the NCI, the current process for activating Phase III trials through its cooperative groups takes more than two years on average, while most Phase I and II trials need over 500 days to get started.

A recent analysis of the process showed not only that many cancer studies failed to reach their accrual goals but that “the complex path to trial activation was characterised by steps that did not ultimately add value to the clinical trial itself”.

The OEWG, whose members come from cancer research in academia, clinical practice, industry and government, as well as the advocacy community, starting reviewing the NCI’s clinical trial activation process in December 2008. Its report outlines 14 initiatives and implementation plans that include both target dates and hard deadlines for the initiation of new clinical trials through the cooperative groups.

As Dr James Doroshow, director of the NCI Division of Cancer Treatment and Diagnosis, recently noted in the NCI Cancer Bulletin, the OEWG has set a target of 300 days for the time between submitting a Phase III concept to the NCI Cancer Therapy Evaluation Program (CTEP) and actual trial activation. Phase III trials will be terminated if they are not activated within 24 months.

For Phase I and II studies, the OEWG’s target is 210 days from submission to trial opening, with a termination deadline of 18 months.

To achieve these objectives, the report recommends:

- Appointing dedicated clinical trial development managers to work on protocol activation

- Real-time project tracking systems that can monitor where a concept/protocol is in the review process, and who is the party responsible for that stage of the process
- More support for protocol development, including dedicated medical writers who could help to reduce the number of protocol revisions

- Policies and procedures that co-ordinate interactions between group members, Phase I/II trialists, and the CTEP

Among the OEWG-recommended initiatives already in hand, administrative supplements are being awarded to all of the NCI cooperative groups to help them develop action plans, hire appropriate staff and acquire project tracking tools, Doroshow pointed out. Supplement requests for 48 of the NCI-designated cancer centres are currently under review.

The CTEP has developed its own action plan to improve efficiency and accelerate protocol activation through more co-ordinated, real-time interactions with the clinical trial community. These changes were initiated at the beginning of April.
The new deadlines for study termination set by the OEWG will come into effect on 1 January 2011.