NCI Clinical Trials Stewardship Initiative

• Introduction
• NIH Policies & Tools for Clinical Trials
• NCI Resources for Clinical Trials
• NIH Informational Resources

Introduction

In 2016, NIH announced the first series of reforms and initiatives to improve quality and efficiency of NIH-funded clinical trials focused on a variety of key points along the lifespan of a clinical trial. NIH had modified existing policies and created new ones that govern research involving human subjects and their participation in clinical trials. These initiatives reengineer the process by which clinical investigators develop ideas for new trials, how NIH reviews and selects clinical trials for support, oversees research progress, and how results are reported to ensure rigor and efficiency in clinical trials.

NCI has taken steps to implement these changes and to achieve more consistency in the conduct and management of clinical trials funded through grants, cooperative agreements, and contracts. Referred to as, “The NCI Clinical Trials Stewardship Initiative,” it continues to build upon NCI’s solid foundation of clinical trials stewardship and is led by a committee of NCI representatives from the various Divisions, Offices, and Centers that support clinical trials. The goal of the initiative is to ensure the following:

• Quality of clinical trials
• Safety of research participants
• Reliability of data
• Dissemination of results
• Appropriate stewardship of funds

NIH Policies & Tools for Clinical Trials

As published in JAMA, Toward a New Era of Trust and Transparency in Clinical Trials , authored by Kathy Hudson, Michael Lauer, and Francis Collins on October 4, 2016, NIH launched a multifaceted effort to improve the quality and efficiency of clinical trials by focusing on changes to:

• The process by which clinical investigators develop ideas for new trials
• How NIH reviews and selects clinical trials
• How NIH supports and oversees research progress
• The process by which results and aggregate data are shared and reported

NIH’s Office of Extramural Research provides additional information on clinical trial requirements for grants and contracts. Specific guidance and tools for various steps in the grant application and contract submission process are listed below.

NIH Definitions and Recommended Training

• NIH Definition of a Clinical Trial
  Establishes the NIH definition of a clinical trial as a research study in which one or more human subjects are prospectively assigned to one or more interventions (which may include placebo or other control) to evaluate the effects of those interventions on health-related biomedical or behavioral outcomes.

• Good Clinical Practice Training for NIH Awardees Involved in NIH-funded Clinical Trials
  Establishes the expectation that all NIH-funded investigators and staff who are involved in the conduct, oversight, or management of clinical trials should be trained in Good Clinical Practice (GCP), consistent with principles of the International Conference on Harmonisation (ICH) E6 (R2).

Human Subjects Research Policy Changes

• Use of a Single Institutional Review Board for Multi-Site Research
  Aims to enhance and streamline the IRB review process for multi-site research so that research can proceed as effectively and expeditiously as possible, eliminating duplicative, administrative, inefficient, and burdensome IRB reviews without diminishing human subjects’ protections.

• Revised Policy and Guidance on Inclusion of Children (Inclusion Across the Lifespan Policy; Effective January 25, 2019)
  Ensures individuals are included in clinical research in a manner appropriate to the scientific question under study so that the knowledge gained from NIH-funded research is applicable to all those affected by the researched diseases/conditions. This policy expands the Inclusion of Children as Participants in Clinical Research Policy to include individuals of all ages.

• Change in Certificates of Confidentiality Policy (CoC)
  CoCs are now issued as a term and condition of award automatically for any NIH-funded project using identifiable, sensitive information that was on-going on/after December 13, 2016. Additionally, physical certificates will no longer be issued.

NIH Policy Changes to the Application Submission and Scientific Review Process

• Funding Opportunity Announcements (FOA) for Clinical Trials
  Requires all applications involving one or more clinical trials to be submitted through an FOA specifically designed for clinical trials. The purpose of this policy is to improve the ability for NIH to identify proposed clinical trials, ensure that key pieces of trial-specific information are submitted with applications, and uniformly apply trial-specific review criteria.

• FORMS-E Application Package and Instructions
  Includes the new Human Subjects and Clinical Trial related information form that consolidates all human subject and clinical trial information and expands the review criteria information required for studies that meet the NIH definition of a clinical trial.

• NIH and FDA Protocol Template for Phase 2 and 3 IND/IDE Clinical Trials
  An NIH-FDA suggested format for a clinical trial protocol template that NIH investigators can use when writing protocols for phase 2 and 3 clinical trials that require Investigational New Drug application (IND) or Investigational Device Exemption (IDE) applications.

• Updated Appendix Policy
  Clarifies the types of materials allowed in the Appendix.

New Policy on Dissemination of NIH-Funded Clinical Trial Information

• Dissemination of NIH-Funded Clinical Trial Information
  Establishes the expectation that all investigators conducting clinical trials funded in whole or in part by the NIH will ensure that these trials are registered at ClinicalTrials.gov, and that results of these trials are submitted to ClinicalTrials.gov.

NCI Resources for Clinical Trials

• NCI Funding Opportunities
  The latest publication of all NCI funding initiatives by type (grants, contracts).

• NCI Introduction to the Grants Process
  Basic information for grant applicants when learning about or navigating the NCI grants process.

• DCTD’s Funding Opportunities
  A list of grant opportunities supported by DCTD, including FOAs that accept clinical trials.

• DCTD Cancer Imaging Program’s Clinical Trial Information
  Information for clinical investigators related to NCI grants and contracts for cancer imaging clinical trials

• Division of Cancer Control and Population Sciences Website: Application Submission & Review
  General information and resources on how to apply for an NCI grant.

NIH Informational Resources

NIH Blogs

• NIH Director’s Blog:  Clinical Trials: Sharing of Data and Living Up to Our End of the Bargain
• NIH Office of Extramural Research, Deputy Director Mike Lauer’s Blog:  Building Better Clinical Trials through Stewardship and Transparency
• Email from Dr. Michael Lauer, Deputy Director for Extramural Research at NIH, to the extramural community

NIH Tools/Guidance for Investigators

• Tool to Determine if Research Meets NIH Definition of a Clinical Trial
• NIH Video — Overview of New NIH Policies on Human Subjects Research
• How to Apply — Application Guide
• NIH Video — New Human Subjects and Clinical Trial Information Form within FORMS-E Packet
• NIH Research Methods Resources — Includes videocasts, references, FAQs, a glossary, a sample size calculator for group- or cluster-randomized trials, and a tutorial.