Colorectal Cancer Coalition

Bureaucracy-busting & Getting Rid of the Zombies

By Nancy Roach, the Founder of C3 and Chair of its Board of Directors

On November 4, the National Cancer Institute (NCI) held the 9th meeting of the Clinical Trials and Translational Research Advisory Committee (CTAC). CTAC advises NCI on the implementation of the 2006 recommendations from Clinical Trials Working Group and the 2008 recommendations for the Translational Research Working Group. There’s more information about NCI’s initiatives here.

I am one of two advocates who serve on CTAC, and as an ex-systems analyst, I’m always looking for ways to make government more efficient and accountable.  At the November 4 meeting, recommendations were presented to increase the efficiency of the clinical trial development process – from the time that a researcher presents a concept to NCI to the time that the trial is actually activated.  Under the leadership of Dr. James Doroshow, NCI and its partners are taking aggressive steps to de-bureaucratize publicly-funded cancer research, which will ultimately benefit patients by putting resources into research instead of process.

Following is a very brief overview of the background and the recommendations, with links to additional documentation. And believe it or not, zombies did come up in the discussion!

Editorial Comment:

C3 has made “bureaucracy-busting” a priority of its research program.  Much of the unproductive process is an unintended consequence of well-intentioned changes that evolved over time.  At the end of the day, patients are best served by an efficient research system that can get answers to important clinical questions safely and quickly.  We applaud the efforts of everyone involved with this effort, and look forward to the implementation of the changes.

Improving Operational Efficiency Initiative – Background

One of the initiatives that came out of the Clinical Trials Working Group was the Operational Efficiency Initiative, which is looking at two areas where operational efficiency could be improved:

• Increasing the rate of patient accrual so that trials can be completed faster
• Identifying and reducing institutional barriers (aka bureaucracy) that stretch the time needed to develop and launch clinical trials

NCI and CTAC took aim at the “institutional barriers” first.  Step one was analysis.  David Dilts and Alan Sandler reviewed and documented the process involved with starting trials.  Their analysis showed many places where the process was broken:

• Starting a phase 3 trial in a cooperative group takes from one to three YEARS
• 40% of phase 3 cooperative group trials enrolled fewer than 20% of the patients needed to get a result
• Trials that take longer than two years to develop enroll fewer patients
• Fixing the system required changes by everyone involved, including NCI and the cooperative groups.

Some problems they identified included:

• Tweaking – multiple reviews that changed “just one thing” which then required an additional round of reviews
• Deadline-denial – when deadlines were broken, there were no consequences
• An inability to say “no” – reviewers would ask submitters to “revise and resubmit” a trial proposal, instead of just saying “no” to the trial.

This is a very quick summary – Dilts’ papers are listed at the end for those who want to learn more, and his very entertaining presentation to NCI is here:

Activating and Opening Phase III Clinical Trials: A Process and Timing Study
Presented at 2007 NCI Clinical Trials Operations Committee (CTOC)

Step two involved further analysis to identify areas that need change. To that end, CTAC formed the Operational Efficiency Working Group (OEWG) which was charged with identifying ways to decrease the time needed to take a trial from concept submission to protocol launch.

The OEWG included 63 members:

• 10 Cooperative Group Chairs
• Pharma/Biotech
• 8 Cancer Center Directors
• Patient Advocates
• Clinical Investigators
• FDA
• Statisticians
• CMS
• Protocol/Trial Specialists
• CTSU
• NCI Clinical Trials Leadership and Staff
• Community Oncologist

The group looked at ways to decrease trial development time without impacting the quality of science or patient safety in 4 types of trials:

• Cooperative Group Phase III Trials
• Cancer Center Investigator Initiated Trials
• Investigational Drug Branch (IDB) Early Drug Development Phase II Trials
• Cancer Center Activation of Cooperative Group Trials

OEWG recommendations

Step 3 was developing the recommendations for what to change and how to change it. The OEWG set timeline targets which dramatically cut the time that NCI, cooperative groups and cancer centers spend on protocol development.  In the chart below, the current median days to activation are shown in blue, and the OEWG targets are in red.  The OEWG targets do not include interactions with Institutional Review Boards (IRB) or industry.  In addition, NCI set firm termination deadlines (green) which provide some “give” to the targets in order to deal with IRBs and industry.

The firm termination deadlines (green) take effect in January 2011.  In other words, if a phase III trial takes longer than 2 years to develop and activate, the trial is terminated.

Here’s where zombies come in. In the past, some trials have hung around the development process for years, clogging up the system.  There wasn’t a clear path to getting those trials out of the system, even though a trial that takes more than two years to develop is very unlikely to succeed. Those trials have been nicknamed zombies.   Effective January 1, 2011, current zombies will be terminated, and the clock will start ticking as new trials enter the system.

The implementation of firm termination deadlines – no excuses allowed – is very new in the public research arena.   In order to get there, OEWG identified 11 specific recommendations which focus on streamlining the development of scientifically significant trials.   The recommendations emphasize:

• Real-time resolution of issues
• Working in parallel processes instead of sequential processes where possible
• Limiting the ability for concept and protocol tweaking
• Use of new specialists such as medical writers and dedicated trial development managers, and new tracking tools so that protocol progress can be monitored.

NCI will provide resources to implement these recommendations over the next year.

The full presentation from the November meeting is online:

Operational Efficiency Working Group (OEWG) Update – Dr. Doroshow (PDF)

The presentation contains more data that explains the timeline decisions, and gets into the detail of the recommendations and the support that will be provided to re-align the protocol development process at NCI, cooperative groups and cancer centers.

The next steps are:

• Prepare Phase I OEWG Final Report and begin implementation
• Launch OEWG Phase II addressing rate of accrual and time to trial completion

The next CTAC meeting is March 3, 2010, and I look forward to hearing a progress report.  These meetings are open to the public, and are held at Building 31, C Wing, 6th Floor, Conference Room 10 at the National Institutes of Health campus, 9000 Rockville Pike, Bethesda, Maryland.

References:

• Development of Clinical Trials in a Cooperative Group Setting:  The Eastern Cooperative Oncology Group, Dilts et al. Clinical Cancer Research, 14(11) June 1, 2008
• Processes to Activate Phase III Clinical Trials in a Cooperative Oncology Group: The Case of Cancer and Leukemia Group B, Dilts et al, Journal of Clinical Oncology, 24(28) October 1, 2006
• Invisible barriers to clinical trials: the impact of structural, infrastructural, and procedural barriers to opening oncology clinical trials. Dilts and Sandler, Journal of Clinical Oncology 24(28) October 1, 2006
• Activating and Opening Phase III Clinical Trials: A Process and Timing Study Presented at 2007 NCI Clinical Trials Operations Committee (CTOC)

This news article was originally posted on November 20th, 2009 and was accurate at the time of publication. Since then, information may have changed or links may now be outdated. Please call our Answer Line 1-877-427-2111 for the latest information, or talk to your doctor before making any medical decisions.

Posted by Nancy Roach on November 20th, 2009

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