Notice Number: NOT-CA-13-012

Key Dates
Release Date: June 14, 2013
Effective Dates: October 5, 2013 for R01 grant applications
September 25, 2013 for P01 grant applications

Related Announcements
PA-16-160

Issued by
National Cancer Institute (NCI)

Purpose

This Notice informs potential applicants that the NCI will no longer use the R01 and P01 activity codes to support investigator-initiated Phase III clinical trials for cancer-related medical interventions and/or investigator-initiated Phase III clinical trials for cancer imaging modalities. Accordingly, the NCI will no longer accept investigator-initiated R01 and P01 applications proposing such clinical trials.

This policy change will be effective for application due dates on and after September 25, 2013 (P01) and on and after October 5, 2013 (R01).

Definitions
For the purpose of this policy, the following definitions apply.

"Cancer-related medical intervention" is defined as any non-behavioral intervention (including new drugs/agents, immunotherapy, cellular therapy, surgery, and/or radiotherapy) with the goal to treat patients with cancer or prevent cancer in individuals not diagnosed with cancer, including symptom control studies (depression, neuropathy, nausea, etc.)

"Cancer imaging" is defined as any imaging modality relevant to cancer and/or cancer co-morbidities.

Background

The NCI has traditionally provided support for all phases of clinical trials and interventions via grants and cooperative agreements (including the R03, R21, R01, P01, U01, U10, and UM1 mechanisms). Historically, the majority of early phase trials have been conducted under R03, R21, R01, P01, U01, and UM1 activity codes, whereas most Phase III clinical trials have been conducted under the U10 activity code, with a limited number of Phase III clinical trials performed under the R01, P01, and U01 activity codes.

An NIH-defined Phase III clinical trial is a broadly based, prospective, clinical investigation. Phase III clinical trials usually involve several hundred or more human subjects each, with the common goal of evaluating an experimental intervention in comparison with a standard or control intervention, or comparisons of two or more existing standard treatments. Often the aims of such investigations are to provide evidence leading to a scientific basis for consideration of a change in health policy or a change in standard of care. The majority of Phase III clinical trials are testing medical interventions. Phase III clinical trials for other types of interventions are less common.

NCI has determined that it is no longer appropriate to support investigator-initiated Phase III clinical trials for cancer-related medical interventions as well as Phase III clinical trials for cancer imaging modalities. In general, medical intervention Phase III clinical trials require more time (from clinical trial protocol development to enrollment, follow-up, and final analysis) than allowed by a single 5-year funding cycle associated with R01 and P01 awards. Spanning a clinical trial over more than one R01 or P01 funding cycle is impractical because the successful renewal of these awards cannot be guaranteed. More appropriate mechanisms for Phase III trials of medical interventions and cancer imaging modalities are/will be available through the NCI National Clinical Trials Network (NCTN, which succeeded the NCI Clinical Cooperative Groups Program), the Community Clinical Oncology Program (CCOP) or its eventual successor.

Policy

NCI will no longer accept R01 and/or P01 applications, starting with the due date of October 5, 2013 for R01 grant applications, and September 25, 2013 for P01 grant applications, that propose Phase III clinical trials to test the efficacy of cancer-related medical interventions including symptom control studies or Phase III clinical trials of cancer imaging modalities. NCI will continue to accept R01 and P01 applications for clinical trials that are limited to public health interventions, comparative effectiveness research (non-medical interventions, behavioral, or health systems research) and other psychosocial, behavioral, and related interventions to address consequences of cancer, provided they can be completed entirely within the 5-year grant cycle.

NCI will continue to accept R01 and P01 grant applications that request support for correlative laboratory studies auxiliary to new and ongoing Phase III clinical trials.

Exception: Renewal (type 2) applications proposing to continue ongoing Phase III efficacy clinical trials/studies currently supported by NCI P01 and/or R01 awards will be permitted until completion of the trial; however, no new Phase III trials may be proposed.

Types of Phase III Clinical Trials that may continue to be supported under the R01 or P01 mechanisms
Some Phase III clinical trials that do not involve medical interventions (i.e., do not test new drugs/agents, surgery, radiation, and/or imaging) may still be submitted under the R01 and/or P01 mechanisms, provided that solid evidence can be presented to assure their completion (conception to final analysis) within a single project period of 5 years.

Examples of Phase III clinical trials that do not involve medical interventions and are expected to have shorter term end-points (so they may be successfully completed within a 5-year funding period) include:

1. Phase III clinical trials for public health interventions that are related to psychosocial, psychopharmacologic, behavioral, educational, or lifestyle factors, or health services intervention and health communication to improve:

• Cancer prevention or cancer treatment efficacy by non-medical interventions addressing, e.g., smoking cessation, vaccine uptake, immune function, screening behavior, or treatment adherence (such studies are not viewed as cancer medical intervention studies);
• Health care delivery by changes in the organization and/or delivery of cancer care (e.g., team-based care; new organizational mechanisms/staffing such as patient navigation; new models of specialized services such as palliative care or survivorship programs); and/or
• Cancer survivorship by addressing cancer survivorship issues (e.g., social function, or caregiver adaptation).

2. Phase III comparative effectiveness research (http://www.nlm.nih.gov/hsrinfo/cer.html) if it involves only behavioral or health systems research.

Inquiries

Please direct all inquiries to:

William C. Timmer, Ph.D.
Cancer Therapy Evaluation Program
Division of Cancer Treatment and Diagnosis
National Cancer Institute
Phone: 240-276-6540
Fax: 240-276-7891
Email: william.timmer@nih.gov