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U.S. National Institutes of Health
Last Updated: 04/04/14

Letter of Intent (LOI)

LOI Instructions

NCI/CTEP Career Development LOI

Background:

NCI-sponsored clinical trials of molecularly targeted agents frequently involve correlative biomarker studies that are geared to provide a better understanding of the effects of agents on their tumor targets. The results of these studies often lead to important scientific observations that move forward anti-cancer drug development. Findings from NCI-supported early phase studies are presented at scientific meetings and are published in peer-reviewed journals, both of which are important for successful career advancement.

Investigators wishing to carry out clinical trials with CTEP IND agents must initially submit a proposal, or Letter of Intent (LOI) outlining a plan for a new clinical study. LOIs may be submitted in response to a solicitation for studies to carry out the CTEP development plan, which is formulated with input from the Investigational Drug Steering Committee and has the concurrence of the industry collaborator. Alternatively, unsolicited LOIs may be submitted by investigators who wish to address novel hypotheses that may be supported by published or unpublished preclinical data.

To ensure that the best science moves forward, along with the best use of NCI resources, both solicited and unsolicited LOIs are evaluated on the basis of a number of criteria, including:

  • Strength of scientific rationale
  • Supporting preliminary data
  • Appropriateness of patient population
  • Adequacy of study design
  • Quality and relevance of laboratory correlatives
  • Ability to accrue and complete study in timely manner
  • Consistency with CTEP development plan
  • Not duplicative
  • Agent availability
  • Industry sponsor concurrence

On average, each year NCI/CTEP receives approximately 400-500 LOIs, of which about 1/3 are approved; nearly 140 new phase 1 and phase 2 clinical trials are activated with agents under an NCI IND. Given the modest success rate for LOI approvals, even for experienced investigators, junior faculty would benefit from a process that would provide them with a competitive advantage, while still maintaining the standards required for an NCI-sponsored clinical trial.

There are NIH grant mechanisms to support junior faculty who are embarking upon a career in clinical research. For example, the Mentored Patient-Oriented Research (POR) Career Development Award (K23) supports the career development of investigators who have made a commitment to focus their research endeavors on patient-oriented research. This mechanism provides support for three to five years of supervised study and research for clinically-trained professionals who have the potential to develop into productive, clinical investigators. Besides government funding mechanisms, there are other resources available for young investigators, such as the ASCO career development awards, and opportunities for training in clinical trial methodology that include the AACR/ASCO and FECS/AACR/ASCO Methods in Clinical Cancer Research meetings that are held each year in Vail, CO and in Switzerland, respectively. Becoming a PI on a clinical trial is an important step for career development: it permits the investigator to acquire experience in trial design and execution, it provides an opportunity to achieve recognition within the research community, and it provides credibility when applying for grant funding.

Career Development LOI Process:

The Career Development LOI is intended to increase the LOI success rate and to facilitate career development of junior investigators. To achieve that goal, the following components have been instituted.

  1. LOI prioritization. Analogous to the process used by study sections to provide a competitive advantage to a grant submitted by junior investigators, LOIs submitted by junior investigators will be prioritized favorably when compared to LOIs submitted by more experienced investigators. When reviewing solicited LOIs for a particular indication or combination, CTEP often finds that several proposals may be of similar quality and in an approvable range. In such cases, where a junior faculty PI has submitted an approvable LOI, he/she would be awarded the study.

    Since a successful outcome requires the submission of an approvable LOI, investigators are encouraged to contact CTEP Investigational Drug Branch staff to obtain their input during LOI preparation.

    This approach should provide junior faculty with a competitive advantage in the LOI submission process, while continuing to maintain the standards of the NCI/CTEP drug development program. Moreover, favoring Career Development LOIs may provide an added incentive for institutional support of junior faculty.

  2. Mentorship and institutional support for junior investigators will be promoted by:

    (a) requiring the identification of a senior faculty mentor and a letter of commitment from the institution to provide the necessary resources necessary to carry out the study. These resources may include, but are not limited to, research nurse, data management and statistical support, and access to patients.

    (b) providing an incentive for institutions to have junior faculty assume the PI role through the prioritization of their LOI submissions.

Submission requirements:

  1. Eligibility:
    1. The PI should have a major interest in clinical research and the intention to develop a career in that field.
    2. He/she should be within 7 years of completion of fellowship training and a faculty member (fellows may not serve as PIs on studies) at an institution with a successful track record in conducting cancer clinical trials (Note: PIs of NCI Cooperative Group proposals are also eligible).
  2. An institutional letter of commitment should be provided, indicating institutional support for the proposed study, including the availability of research nursing staff, data monitoring, and support from relevant departments/institution or groups to help conduct the proposed clinical trial.
  3. A senior faculty member should be identified who will serve as a mentor and provide expertise and oversight in the design and conduct of the trial. In an accompanying letter, the mentor should confirm the feasibility of the proposed trial within the institutional setting and indicate a commitment to enabling the PI to conduct clinical trial successfully.
  4. An LOI for a clinical trial utilizing a CTEP-held IND agent(s) and meeting the evaluation criteria listed above.
  5. The LOI should be submitted with the required documentation:
    1. PI's curriculum vitae
    2. Letters of commitment from the faculty mentor and the institution.