A Manual for Participants in Clinical Trials of Investigational Agents ...

7 The Letter of Intent, Concept, and Drafting of a Protocol
Planning and Execution of a Clinical Trial
The following five sections describe the investigator’s responsibilities for implementation
of a clinical trial, from drafting the protocol to study completion. They guide the protocol
chair and participating investigators and outline NCI policies on their responsibilities in
clinical trial execution.
7.1 The Letter of Intent (LOI) or Concept
7.1.2 Definition
The Letter of Intent (LOI) is an investigator's declaration of interest in conducting a
phase 1 or 2 trial (excluding randomized phase 2 trials of at least 100 patients)with a
specific investigational agent in a particular disease. CTEP’s approval of the LOI
reserves that "slot" for the investigator's protocol if it is submitted within a defined time
frame. Approval also signifies agreement that the investigator shall submit a protocol
based on the terms stated in the LOI. The Concept serves the same purpose for phase 3
and randomized phase 2 trials (>100).
7.1.3 Purpose
CTEP has devised the LOI system to maximize the efficiency and fairness by which it
allocates experimental agents to investigators for study. Proper use of the system
ensures a steady flow of new agents into the clinical trials system. It enables CTEP to
plan the development of several agents simultaneously. For investigators, the LOI
system also saves time and effort, because its use should spare them from writing a
protocol unlikely to be approved. Protocols submitted subsequent to favorable review of
an LOI are much more likely to be approved without request for major modification,
because many of the crucial features of a phase 2 proposal must be specified in the LOI
itself. The LOI system also is used for submission of combination pilot studies. In these
cases, reviews typically focus on the rationale for agent combinations, the proposed
sample size, and the adverse events of each agent when given alone. The system also
provides the investigator with an opportunity to explore the proposal with CTEP staff at
the concept stage.
7.1.4 Ground Rules for the LOI System
Investigators must submit LOIs for phase 1 or 2 trials that include a CTEP investigational
agent according to the following schedule:
• Agents Beginning Phase 1 - In advance of the IND submission, CTEP will
announce the availability of an agent, issue a request for proposals for phase 1
trials and provide a deadline for the submission of LOIs
• Agents Beginning Phase 2 - In late phase 1, CTEP will issue a request for
proposals for initial phase 2 trials including a deadline for submission of LOIs.
• All Other Phase 2 Trials - After this deadline has passed, investigators may
submit LOIs at any time.
Each phase 1 or 2 protocol must be preceded by an approved LOI. Our experience
demonstrates that protocols submitted without a previously approved LOI are more likely
to be rejected as unnecessarily duplicative or needing major modification. If a phase 1 or
2 protocol is submitted without a prior LOI having been submitted, CTEP notify the the
Section 7 - Investigator’s Manual 2009 30