Concept Procedures for Clinical Trials
The following procedures are designed to provide assistance and program advice to prospective applicants for Phase I, II, or III clinical trials. For Phase III clinical trials, the NIDCD will give priority to proposals that are likely to have a major impact on public health policy and/or clinical practice, or that will provide important new information to health providers and consumers.
Before applying for a grant to develop and conduct a clinical trial, investigators are encouraged—but not required—to first contact the clinical trials program officer to ensure that the concept serves one of the NIDCD mission areas (hearing, balance, taste, smell, voice, speech, or language). This will allow program staff to guide investigators in submission of their applications. The program officer will ask the potential applicant to submit a brief concept proposal that includes the following information:
(For phase I trials, skip items that do not apply.)
- List the title of the proposed research, the principal investigator(s) and institution(s).
- If prior clinical study experience is minimal, appoint clinical study expert(s) as key personnel to help with study design and execution.
- Appoint a biostatistician—preferably with clinical study experience—as key personnel.
- Describe the target disease, primary study objective, and any secondary study objectives.
- Briefly describe the scientific rationale for the study. State the compelling public health need and the study’s potential impact on medical care.
- Briefly describe the study design and indicate, in general terms, how the design will fulfill the intent of the study. For a preliminary phase I or II clinical study, describe how it will be used to formulate a definitive phase III clinical study.
- U01 and U34 applications require compelling preliminary data. Are preliminary data adequate to use one of these mechanisms?
- Describe the informed consent process and human subjects protections. If risks are minimal, describe a data safety plan. Describe how adverse events will be reported.
- If risk is significant (more than minimal), appoint an independent medical officer to help manage adverse events. Is a Data and Safety Monitoring Board required or requested? Describe a detailed adverse event reporting plan (see NIDCD Guidelines for Data and Safety Monitoring of Clinical Studies).
- If risk is significant (more than minimal), describe an interim monitoring plan, including the schedule of interim analyses and guidelines for stopping the study for reasons of safety.
- Consider ethical considerations of the proposed research. For example, placebo-controlled trials may be unethical if a standard-of-care exists.
- List specific inclusion and exclusion criteria. How will these criteria affect volunteer recruitment and retention? Describe the method for identifying and recruiting participants.
- Describe the number of participants to be enrolled and the number of clinical sites needed to meet target enrollment.
- Describe the statistical and clinical basis for the sample size calculation.
- Describe the extent and type of blinding/masking. If possible, persons measuring the primary outcome should be masked.
- Describe the randomization procedure.
- Describe how the intervention will be administered, including dose and duration as applicable.
- How will fidelity checks be used to ensure that each subject receives the correct treatment?
- Define the primary and secondary outcomes and how they will be measured. List the statistical methods to be used to analyze these outcomes. Specify whether an intention-to-treat analysis will be performed.
- Explain how missing data, outliers, noncompliance, and losses to follow-up will be handled in the analyses.
- Describe how data will be created, handled, and stored. How will data integrity and confidentiality at individual sites be confirmed? Double-blind trials require an independent data coordinating center.
- Specify stopping rules for efficacy, futility, or poor study performance. For phase I and II studies, specify an efficacy threshold needed to progress to a phase II or III trial.
- Avoid underestimating trial duration. Allow ample time for start-up, planned enrollment, follow-up to endpoint, and close-out.
- Avoid underestimating trial cost. For phase II and III trials, budget for a clinical coordinating center, data coordinating center, and Data and Safety Monitoring Board, as needed.
- For a new drug or device, try to obtain an IND, IDE, or written exemption from the FDA before submitting the grant application. Letters of Approval can be sent after submission, and will be included in review if received 30 days in advance.
- Name the participating pharmaceutical or device manufacturing company, if any.
- Do you or any member of your study team have a financial conflict of interest or hold a patent with the use of the intervention in this protocol?
- For phase II and III trials, have you considered collaborating with an NIDCD clinical research network such as Creating Healthcare Excellence through Education and Research (CHEER)?
- Estimate direct costs for all years of funding. Notify the program officer 30 days before submission if you are requesting $500,000 direct costs in any year.
- Indicate a planned submission date.
Our goal is to help researchers prepare complete applications by ensuring that all critical elements are addressed in the application. The NIDCD program officer and other staff provide applicants with a critique of the study based on the responses. As is always the case, reviewers may or may not agree with NIDCD recommendations and suggestions. The applicant and study team are ultimately responsible for ensuring that the clinical trial application is complete.
For more information, contact:
Gordon B. Hughes, M.D., Director, Clinical Trials, Division of Scientific Programs, NIDCD
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