Clinical Research Management

Walter J. Koroshetz, M.D.

Deputy Director, National Institute of Neurological Disorders and Stroke

NIH View of clinical trial management. A conversion to:

• Time– Rate of advances dependent on time to execute the trial. – Neuroscience no longer the bottleneck

• Money– Number of trials limited by available funds

• Time=money– The ”Big Dig” effect of ballooning trial budgets

• Human resources– Researchers– Patients

• Quality clinical data is still #1.– Respected by the community of patients and doctors.– Relevant to the public health.

NIH View of Clinical Trial Management and the CTSA

• A unique opportunity with new strength in numbers.

• Intellectual power and the will to come together to solve problems.– Time through IRB– Time through contracts– Improved efficiency: Number of steps, cycles, errors,

repetitions.– Improved enrollment processes. – Create research resources to support a new level of

quality and efficiency?

Clinical Research ManagementGood Bad

At least its managed. Dr. C.M. Fisher flipped a coin, kept a notebook, clinical research integrated into his practice.

Delays, Tremendous effort required that is separate from actual patient investigation. Less joy?

Conflict of interest now on the radar screen

Tremendous duplication of disclosures. Tremendous effort to review of disclosures. Researchers often viewed with suspicion.

Better funded. More expensive. It’s now an enterprise with all the ramifications. Cost, oversight, infrastructure, .

More advanced technology More expensive and time intensive to set up the technology. More difficult to jump in with armed with a good idea.

Patients better protected Difficult for uninitiated to balance disease specific risk and benefit –whether IRB, FDA or patients.Enrollment can be very difficult.

More opportunities for funding Obtaining funding is becoming a full time job.

Is It Ugly Yet?

Copyright restrictions may apply.

Sung, N. S. et al. JAMA 2003;289:1278-1287.

The 2 Translational Blocks in the Clinical Research Continuum

Copyright © American Society of Clinical Oncology

Dilts, D. M. et al. J Clin Oncol; 24:4545-4552 2006

Level 0 process flow map for opening an oncology clinical trial

Copyright © American Society of Clinical Oncology

Dilts, D. M. et al. J Clin Oncol; 24:4545-4552 2006

Timeline for opening of an

oncology clinical trial

And now you want to open sites overseas!

Solutions?

Process Barriers:From the NINDS Stroke Progress Review

Group

Delays in submission, review, start up of clinical trials.

Regulatory requirementsNIH and FDA Industry partnershipsIRBContracts

Process Barriers

• “Establishing subcontracts for clinical sites has emerged as the most common, rate-limiting step in study initiation”

• Issues:– indemnification – intellectual property – institutional control– economic costs of tests that are outside of the

local investigator’s control.

Potential for Progress

• Issues:– Lack of communication between institutions

• Harmonization (NINDS and CMS), (NINDS and FDA)• Harmonization of contract processs among research

institutions.– Inefficient data management

• Central web-based data management platform– Common data elements, – Data entry system with cross checks– Follow-up appointments programs– QA monitoring

– Inability to build on previous trial data• Harmonized outcome measures• Data repository

Potential for Progress

• Training • Metrics for value:

– Propose a standard methodology for use by grant applicants to assess economic and societal impact of clinical trial.

• NINDS ImPACT Program: Fostering Immediate Practice-Altering Clinical Trials

NIH

• The 15 ICs present look forward to the workshop

• A hearty thanks to the participants for sharing their ideas and brain power.

• We will take back lessons and work with you to improve the process.

How to get people like this to make contributions to medicine?