Both applications undergo peer review simultaneously. Multi-site clinical trials are defined as trials that enroll from two or more recruitment sites. Multiple sites are necessary for efficacy trials to increase generalizability of findings and enhance recruitment efficiency as well as representativeness of the participants.
In addition to scientific relevance and excellence, these clinical trials are expected to be conducted with a high degree of efficiency, with streamlined administrative procedures wherever possible. This FOA invites cooperative agreement applications for investigator-initiated, multi-site, clinical trials Phase III and beyond to study the effects of natural products in NCCIH designated areas of high research priority. Proposed clinical trials may utilize a design anywhere along the continuum between explanatory and pragmatic.
For this FOA, pragmatic trials are considered those that test an intervention under the usual clinical conditions in which it will be applied, while explanatory trials do so under more idealized circumstances. The trial design should be appropriate for the study question. This FOA is appropriate when there a clear and compelling rationale, a rigorous empirical basis, and scientific premise, which should include preliminary data from animal studies and previous human studies.
The following preliminary data from human studies preferably published in the peer-reviewed literature on the same product and specific formulation as proposed in the current application are required:. For the purposes of this FOA, it is preferred that there be an established, measurable, reproducible, well-characterized biological signature for a given natural product in human subjects.
However, NCCIH acknowledges that for some conditions, it may be impossible or impractical to directly measure the biological impact of a natural product. In these circumstances the study should be justified by: 1 a clear rationale for why studying a biological signature in human participants is impossible or impractical; 2 potentially proposing other objective, reproducible measures, that may be proxy to, or indicative of a biological or behavioral effect for the natural product; and 3 strong compelling preliminary data to warrant further study of a natural product in clinical studies.
There should be clear objectives for both a UG3 and a UH3 phases. The UG3 phase will support the development of case report forms and other resources necessary to the performance of the trial; further development and finalization of study partnerships including signed contracts with performing clinical sites; single Institutional Review Board as well as Data and Safety Monitoring Board approval of the trial protocol, informed consent s , manual of operations, and clinical trial project management plans.
Applications that provide a clinical trial project management plan that delineates how the study will monitor and evaluate critical processes impacting feasibility of trial launch, conduct, and completion, coupled with on-time and on-budget performance milestones are strongly encouraged. All regulatory approvals should be obtained prior to the end of the UG3 award. Provision of the necessary natural products, matched placebos, or other resources should be planned at the start of the UH3 award to allow for the successful launch and execution of the proposed clinical trial in the UH3 phase.
Subject to NCCIH funding availability and scientific priorities, UH3 awards will be made after administrative review with attention to the extent to which agreed upon milestones have been met. Utilization of milestones is a key characteristic of this FOA. A milestone is defined as a scheduled event in the project timeline, signifying the completion of a major project stage or activity. Plans must be guided by milestones that will be reached at the end of the UG3 phase. Milestones are to be performance-based to achieve completion of the trial on time and on budget.
UG3 projects that have met milestones will be assessed administratively to determine eligibility for transition to the UH3 implementation phase. This FOA will support applications that include a series of milestones for completion of the clinical trial UH3 phase and provide contingency plans to proactively confront potential delays or disturbances in attaining the milestones.
Continuation of the award is conditional upon satisfactory progress and subject to availability of funds. If, at any time, recruitment falls significantly below the projected milestones for recruitment, the NCCIH will consider ending support and negotiating an orderly phase-out of the award and retains, as an option, periodic external peer review of progress.
NCCIH staff will closely monitor progress at all stages, milestones, accrual, and safety. Particular focus is on management of conditions for which natural products are widely used by the public and where there is evidence of postulated mechanisms of action. Applications proposing research topics not identified above as high programmatic priority will be considered of lesser or low programmatic priority, which will significantly influence programmatic relevance and reduce the likelihood of funding.
The following types of clinical trials are not responsive to this FOA and applications proposing such activities will be deemed non-responsive and will not be reviewed:. Early contact 12 weeks prior to submission is encouraged provides an opportunity for IC staff to discuss the scope and goals, and to provide information and guidance.
Other Information for award authorities and regulations. Cooperative Agreement: A support mechanism used when there will be substantial Federal scientific or programmatic involvement.
Substantial involvement means that, after award, NIH scientific or program staff will assist, guide, coordinate, or participate in project activities. See Section VI. Only those application types listed here are allowed for this FOA. Need help determining whether you are doing a clinical trial? The number of awards is contingent upon NIH appropriations and the submission of a sufficient number of meritorious applications. Application budgets are not limited but need to reflect the actual needs of the proposed project.
The scope of the proposed project should determine the requested project award period. The period of award for the UH3 phase is expected to be 4 years. With strong justification, up to 6 years for the UH3 may be requested. Non-domestic non-U. Entities Foreign Institutions are not eligible to apply. Organizations are not eligible to apply. All registrations must be completed prior to the application being submitted. Registration can take 6 weeks or more, so applicants should begin the registration process as soon as possible.
The NIH Policy on Late Submission of Grant Applications states that failure to complete registrations in advance of a due date is not a valid reason for a late submission. Obtaining an eRA Commons account can take up to 2 weeks. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH support.
Applicant organizations may submit more than one application, provided that each application is scientifically distinct. The NIH will not accept duplicate or highly overlapping applications under review at the same time. This means that the NIH will not accept:. This FOA only accepts applications that are part of a collaborative set of multiple applications. See your administrative office for instructions if you plan to use an institutional system-to-system solution. Although a letter of intent is not required, is not binding, and does not enter into the review of a subsequent application, the information that it contains allows IC staff to estimate the potential review workload and plan the review.
By the date listed in Part 1. Overview Information , prospective applicants are asked to submit a letter of intent that includes the following information:. Martina Schmidt, Ph. Telephone: Email: schmidma mail. Titles may not exceed characters in length, including the tag, e. The Cover Letter is one pdf file only.
Each site should submit an identical listing. If applicable, the letter should indicate the name of the NCCIH program officer with whom the project has been discussed. Other Attachments : The attachment listed below must be completed and attached or the application will not be peer reviewed. The Project Management Plan should describe the evidence-based strategy that will be used throughout the project to ensure that the unique goals of the clinical trial are met.
Project management planning should directly support the needs of scientific study leadership to identify barriers, make timely responses, and optimize the allocation of limited resources to meet pre-defined study objectives. The project management plan should describe the planning team and identify control points and processes that are key to scientific and fiscal performance.
This will include a description of the organizational strategy that defines internal control points and business roles. The management plan should also describe how the team, in collaboration with the DCC, will proactively evaluate and prioritize issues that jeopardize study goals and lead to the development of corrective responses to resolve fiscal and logistical issues risk planning in a timely manner.
Describe processes required for orderly project closure. In summary, the project management plan should provide sufficient detail to demonstrate the ability to achieve the goals of the clinical trial on-budget and on-time. The project management plan should include risk mitigation or contingency plans.
Biographical Sketches : The application for the CCC must include only the personnel and corresponding biographical sketches for the key personnel for that application. All personnel involved in the conduct of the clinical trial are Key Personnel and must provide an NIH Biosketch whether or not they are budgeted. The experience of all key personnel must be carefully documented. Most clinical trials will require a multidisciplinary team clinician, statistician, data manager, study coordinator s , etc.
If parts of the costs of the trial are to be provided by sources other than NCCIH, these contributions must be presented in detail in the budget justification. Include budget support for the publication and dissemination of results. An independent DSMB will be established to monitor data and oversee participant safety in the clinical trial.
The Research Strategy should be organized in a manner that will facilitate peer review. The body of the application should present an overview of the state of the science, current status and relevance of the trial, a discussion of the specific protocol, and the approach to data collection and analysis.
Significance : The significance of the proposed clinical trial and importance of the question must be clearly stated. It is particularly important that there be a discussion of how the trial will test the proposed hypotheses and why there is clinical equipoise. The application should make clear the need for and timeliness of the study with emphasis on how the results will address an evidence gap and therefore advance our knowledge of theory and practice in this area.
A discussion of the costs and benefits of the study should be included for evaluation of the trial's significance. Innovation: Explain how the application challenges and seeks to shift current research or clinical practice paradigms.
Approach : The research approach section should include a description of the supporting data including strengths and weaknesses of the published literature , clinical trial experience, the experimental approach, and a milestone plan. Supporting Data : The studies that led to the proposed clinical trial should be presented.
Data from pilot studies that show the need for and the feasibility of the trial should also be presented. Additional supporting data from other research should be included so that the approach chosen is clearly justified and adequately framed.
Applications must include the following preliminary data from human studies of the same product and specific formulation as proposed in the current application preferably published in the literature :. Experimental Approach : The proposed experimental approach should include an appropriate design and the rationale for the particular design chosen e. The experimental approach description should include:.
Letters of support from clinicians or clinical department chairs whose support is necessary to the successful conduct of the trial should be provided. Applicants are also encouraged to include documentation of the commitment of any subcontractors and consultants, as well as service agreements for personnel or facilities.
Letters of commitment must be co-signed by the business official of the collaborating center. In addition, a letter of support should document that sufficient supply of the natural product will be available for testing at the time of award, including expiration date; the supplier will meet CMC specifications; and the supplier will provide the data necessary for the investigator to adhere to NIH and FDA policies. Documentation should include a letter of agreement from the 3rd party supplying the natural product.
If parts of the costs of the trial are to be provided by sources other than NCCIH, provide Letter s of Support signed by an authorized representative.
Applicants must provide strong evidence of the availability of appropriate institutional resources, and suitable patient populations. Documentation of availability of eligible subjects at clinic sites, presented in tabular format must be provided. The application must include relevant information that addresses the feasibility of recruiting participants who are eligible for the clinical study or trial. Specifically, applicants must provide evidence that each recruiting center in the study or trial has access to a sufficient number of participants who meet the eligibility criteria as defined in the submitted protocol.
For multisite applications, information must be provided for each participating site. In addition to the NIH application requirements for a data and safety monitoring for clinical trials, NCCIH requires independent monitoring for research involving human subjects.
Subsequently, the DSMB will monitor and review recruitment, adverse events, data quality, outcome data, and overall awardee performance. The DSMB has the responsibility to review interim data and final data, and recommend whether the protocol should be modified, and, at each meeting, whether the study should be continued or should be terminated early.
Thus, its ethical responsibilities, to the participants as well as to the integrity of the study, are of paramount importance to the NCCIH. The DSMB will meet in person or by phone at least twice a year. Applicants should not propose DSMB members in the application, or even inquire about the interest of possible DSMB members, because anyone so contacted would not be eligible to serve as a member of the peer reviewer committee that will evaluate the applications for scientific merit.
For renewal applications, applicants should provide a list of the DSMB members in the application. The Overall Structure of the Study Team attachment should describe the study organization and administration, and include a communication plan. The attachment can include, but is not necessarily limited to: a description of committee structures needed to manage the complexity of the trial; the role of any internal or external advisory committees; the oversight, responsibilities, and coordination of any sites or cores proposed; and the role of any sub-contractors or providers of services, personnel, or facilities.
The plan should explain how these will integrate with the organizational framework described in the collaborating DCC application and should address how the CCC and DCC will coordinate leadership for clinical trial implementation.
The communication plan should include a description of the coordination between the separate components including NCCIH and identify the key channels used to reach and inform each stakeholder group and receive feedback. The proposed clinical trial must use a natural product such as botanical, herbal, dietary supplement, probiotic, vitamin or mineral for this FOA.
Investigators should describe the process that will be used for attaining all necessary FDA or other applicable regulatory agency approvals necessary to the conduct the trial; and associated timeline to complete these approvals.
If the protocol is conducted under a non-US regulatory agency the applicant should submit a plan for attaining those regulatory approvals. Describe how the CCC will facilitate and support timely publication and dissemination of results as appropriate and consistent with achieving the goals of the program. The following attachments must be included as a part of the cooperative agreement application. Attachments permit expansion of certain elements that cannot be appropriately described in the Research Strategy.
All attachments listed below must be provided or the application will not be peer reviewed. Applicants must provide a detailed table listing the characteristics of trials that demonstrate Key Personnel experience in trial coordination in the last 5 years. One table must be provided for each study record with a unique filename for each study record as an attachment e.
One Milestone Plan must be provided for each study record with a uniqe filename for each study record e. The plan should describe the key milestones that need to be met throughout the lifecycle of the clinical trial UG3 and UH3 phases to ensure its success; the processes that will be used to reach the milestones; and a timetable identifying when each of these key milestones will be met this can be provided as a table or a graph.
All applicants must use the following definition of a milestone in their application: a scheduled event in the project timeline that signifies the completion of a major project stage or activity. Milestones must be relevant, achievable, and measurable.
The milestone plan should include anticipated challenges to meeting milestones and propose potential mitigation or corrective actions strategies. UH3 milestones should address overall recruitment and retention goals.
CCC milestones of particular interest during the UG3 phase that should be described in the application may include but are not limited to:. The application should also include a series of milestones for the completion of the specific aims of the clinical trial UH3 phase and contingency plans.
CCC milestones of particular interest during the UH3 phase that should be included in the application include but are not limited to:. Submission of study results to ClinicalTrials.
Award continuation, even during the period recommended for support, is conditional upon satisfactory progress. NCCIH staff will closely monitor progress at all trial stages including milestones, accrual, and safety. Note: Delayed onset does NOT apply to a study that can be described but will not start immediately i. See Part 1. Section III.
Part I. Overview Information contains information about Key Dates and times. Applicants are encouraged to submit applications before the due date to ensure they have time to make any application corrections that might be necessary for successful submission. When a submission date falls on a weekend or Federal holiday , the application deadline is automatically extended to the next business day. Organizations must submit applications to Grants. NIH and Grants.
Each application of a collaborative set must be on-time. Applicants are responsible for viewing their application before the due date in the eRA Commons to ensure accurate and successful submission. This initiative is not subject to intergovernmental review.
The details of the IND status of the natural product should be provided in the attachment included in the study record for section 4. If the FDA has granted a waiver for the trial proposed in the application, then the applicant can provide this letter as part of the response to item 4. If the protocol is conducted under a non-US regulatory agency, then equivalent determinations and documentation must be provided to NCCIH prior to a grant award.
Funding will not be made until the necessary regulatory approvals are in place for the conduct of the proposed clinical trial. Again, no awards will be made until all necessary DEA licenses and registrations are in place.
Paper applications will not be accepted. Applicants must complete all required registrations before the application due date. Eligibility Information contains information about registration. For assistance with your electronic application or for more information on the electronic submission process, visit How to Apply — Application Guide.
If you encounter a system issue beyond your control that threatens your ability to complete the submission process on-time, you must follow the Dealing with System Issues guidance. See more tips for avoiding common errors. Upon receipt, applications will be evaluated for completeness and compliance with application instructions by the Center for Scientific Review, NIH. Applications that are incomplete or non-compliant will not be reviewed. Each application of a collaborative set must be complete and compliant.
Applicants are required to follow the instructions for post-submission materials, as described in the policy. Any instructions provided here are in addition to the instructions in the policy. Only the review criteria described below will be considered in the review process. A proposed Clinical Trial application may include study design, methods, and intervention that are not by themselves innovative but address important questions or unmet needs.
Additionally, the results of the clinical trial may indicate that further clinical development of the intervention is unwarranted or lead to new avenues of scientific investigation. Reviewers will provide an overall impact score to reflect their assessment of the likelihood for the project to exert a sustained, powerful influence on the research field s involved, in consideration of the following review criteria and additional review criteria as applicable for the project proposed.
Reviewers will consider each of the review criteria below in the determination of scientific merit, and give a separate score for each.
An application does not need to be strong in all categories to be judged likely to have major scientific impact. For example, a project that by its nature is not innovative may be essential to advance a field. Does the project address an important problem or a critical barrier to progress in the field? Is the prior research that serves as the key support for the proposed project rigorous? How will successful completion of the aims change the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field?
For trials focusing on clinical or public health endpoints, is this clinical trial necessary for testing the safety, efficacy or effectiveness of an intervention that could lead to a change in clinical practice, community behaviors or health care policy?
For trials focusing on mechanistic, behavioral, physiological, biochemical, or other biomedical endpoints, is this trial needed to advance scientific understanding? If the primary outcomes of the trial are achieved, how critical will the information be to addressing the evidence gap and advancing knowledge of theory and practice? Could results of the trial have a significant influence on clinical care and improve health? Is there sufficient demonstration for the presence of equipoise?
Is there a sufficient and consistent body of relevant preclinical or clinical research of high scientific rigor to support the study rationale? If Early Stage Investigators or those in the early stages of independent careers, do they have appropriate experience and training? If established, have they demonstrated an ongoing record of accomplishments that have advanced their field s?
Do they have appropriate expertise in study coordination, data management and statistics? For a multicenter trial, is the organizational structure appropriate and does the application identify a core of potential center investigators and staffing for a coordinating center? How well defined are their roles and responsibilities? Have the investigatorsprovided sufficientevidence to ensure that the clinical centers will employ the appropriate personnel to recruit subjects and implement the clinical protocol?
How well does the application provide evidence of necessary experience and expertise of the investigators with the natural product, the study population, and the research methods to be employed? Does the investigative team have a track record of publishing the results of clinical trials previously completed? How strong is the evidence is provided to demonstrate that the investigative team has successfully conducted clinical trials under an Investigational New Drug IND application or DEA regulations if applicable?
Does the application challenge and seek to shift current research or clinical practice paradigms by utilizing novel theoretical concepts, approaches or methodologies, instrumentation, or interventions? Are the concepts, approaches or methodologies, instrumentation, or interventions novel to one field of research or novel in a broad sense?
Is a refinement, improvement, or new application of theoretical concepts, approaches or methodologies, instrumentation, or interventions proposed?
For Phase III clinical trials, has the investigator sufficiently described how the proposed clinical trial will change clinical practice or practice guidelines? Does the proposed research have the potential to advance the field even if the proposed study design, methods, and intervention are not innovative?
Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the project? Have the investigators included plans to address weaknesses in the rigor of prior research that serves as the key support for the proposed project?
Have the investigators presented strategies to ensure a robust and unbiased approach, as appropriate for the work proposed? Are potential problems, alternative strategies, and benchmarks for success presented? If the project is in the early stages of development, will the strategy establish feasibility and will particularly risky aspects be managed?
Have the investigators presented adequate plans to address relevant biological variables, such as sex, for studies in vertebrate animals or human subjects? Is the trial appropriately designed to conduct the research efficiently? Are potential ethical issues adequately addressed? Is the process for obtaining informed consent or assent appropriate?
Is the eligible population available? Are the plans for recruitment outreach, enrollment, retention, handling dropouts, missed visits, and losses to follow-up appropriate to ensure robust data collection? Are the planned recruitment timelines feasible and is the plan to monitor accrual adequate? Are the plans to standardize, assure quality of, and monitor adherence to, the trial protocol and data collection or distribution guidelines appropriate?
Is there a plan to obtain required study agent s? Does the application propose to use existing available resources, as applicable? Are planned analyses and statistical approach appropriate for the proposed study design and methods used to assign participants and deliver interventions?
Are the procedures for data management and quality control of data adequate at clinical site s or at center laboratories, as applicable? Have the methods for standardization of procedures for data management to assess the effect of the intervention and quality control been addressed?
Is there a plan to complete data analysis within the proposed period of the award? What strengths and weaknesses are there in the study design? How efficient is the trial design? How strong is the evidence for equipoise?
How well does the Clinical Protocol Synopsis attachment describe the necessary elements of the clinical trial and how likely is it that the protocol can be efficiently implemented at all of the sites? How strong are the formative clinical studies, including any pilot studies, underpinning the trial?
Is the natural product appropriately characterized? Does the application provide sufficient evidence to justify that the study population has been appropriately defined? How well does the Recruitment and Retention plan provide evidence that the accrual goals can be reached? Are adverse events appropriately captured and monitored? How effectively does the Project Management Plan identify and describe risks to implementation and how well are contingency plans described?
How clear is the communication plan between DCC and CCC leadership and is it appropriate for implementing and conducting the trial? Because this is a multi-center application, is there evidence of the ability of the individual centers to: 1 enroll the proposed numbers, 2 adhere to the protocol, 3 collect and transmit data in an accurate and timely fashion, and 4 operate within the proposed organizational structure? If the clinical trial is Phase III, does the application include all relevant data to assess whether or not the trial should include adequate numbers of subgroups of participants to allow for separate and adequately powered analyses?
Will the scientific environment in which the work will be done contribute to the probability of success? Are the institutional support, equipment and other physical resources available to the investigators adequate for the project proposed? Will the project benefit from unique features of the scientific environment, subject populations, or collaborative arrangements?
Does the application adequately address the capability and ability to conduct the trial at the proposed site s or centers? Are the plans to add or drop enrollment centers, as needed, appropriate?
How strong are the facilities and resources and does the investigator sufficiently justify they are available to adequately coordinate multi-sites clinical trials? Is there strong evidence that the institutions have the available resources needed to conduct a multi-site trial at the CCC and the performance sites?
How well does the application document the availability of the requisite eligible subject pool in proposed clinical site s? Is there sufficient documentation of the commitment of any subcontractors and consultants, as well as service agreements for personnel and facilities?
As applicable for the project proposed, reviewers will evaluate the following additional items while determining scientific and technical merit, and in providing an overall impact score, but will not give separate scores for these items.
Is the study timeline described in detail, taking into account start-up activities, the anticipated rate of enrollment, and planned follow-up assessment? Is the projected timeline feasible and well justified? Does the project incorporate efficiencies and utilize existing resources e. Are potential challenges and corresponding solutions discussed e. How strongly do the milestones address the specific aims of each phase?
Are the listed milestones appropriate for the goals of the project? To what extent are the milestones relevant, measurable, achievable, result-focused and timebound? Is the proposed Data and Safety Monitoring Plan appropriate for the proposed clinical trial?
Protections for Human Subjects. The investigator and occasionally others may have the only relevant knowledge regarding the treatment because these are the first human uses. A DSMB is often used for studies with high-risk interventions or in vulnerable populations e.
The implementation of this approach should be part of the monitoring plan. A confirmatory clinical trial evaluating the clinical activity of exposure such as a Phase II trial typically follows early exploratory studies and provides more information regarding risks, benefits, and monitoring procedures. Since these studies are often blinded, involve more participants, and are critical to informing decisions for Phase III or pivotal trials, a DSMB is more commonly used.
The NIH requires data and safety monitoring in the form of DSMBs for multi-site clinical trials involving interventions that entail potential risks to participants, and generally for Phase III clinical trials. These large clinical trials compare a new intervention or procedure to a standard intervention or procedure or to no intervention. Treatment allocations are randomly assigned, and the data are usually masked.
Such studies involve several clinical sites and usually involve a large number of participants followed for longer periods of treatment exposure. The implementation of this approach should be part of the monitoring plan for clinical use studies. The organization, responsibilities, and operation of the DSMB are described below. For studies co-funded with other institutes or centers ICs , the lead IC will be responsible for monitoring the study and approving a DSMB if necessary.
The DSMB is responsible for oversight of the activities related to the conduct of the clinical trial to ensure patient safety; conformance to the clinical protocol; overall performance of the study components, such as the study chair office, coordinating center, and clinical sites; and integrity of the data being collected. Each clinical trial supported by the NIDCD has gone through the NIH peer review process plus secondary review by its national advisory board; therefore, it is not the role of the DSMB to serve as a peer review group to redesign any portion of the study, unless the DSMB feels that patient safety or data validity is compromised under the proposed design.
Tasks include but are not limited to the following:. The names of prospective DSMB members should not be included in the clinical trial grant application. The DSMB shall consist of voting members with expertise necessary to interpret data from the trial including biostatistics, clinical trial methodology, ethics, specialty areas of medicine, and laboratory sciences as appropriate.
Selection will be based on experience, knowledge of clinical study methodology, participation on other DSMBs, and absence of apparent conflicts of interest, including financial, proprietary, or intellectual conflicts. In some instances, NIDCD program staff may serve as non-voting ex officio members, affirming objectivity about the outcome s of the trial but not attempting to influence the recommendations of the DSMB.
The voting members of the DSMB will be reimbursed for expenses related to serving on the board through funds provided by the NIDCD to either the study chair's cooperative agreement or the coordinating center's cooperative agreement. These funds will be used to reimburse each member for travel expenses coach fare only , hotel costs, and per diem at the U. The frequency of DSMB meetings will depend on the nature of the study.
A DSMB should meet at least annually. Meetings are generally divided into four parts:. The DSMB has the right to request and review unmasked data by treatment group or by individual subject at any time if the DSMB feels these data are necessary to evaluate safety or other aspects of the trial. A majority vote is required to carry any issue. Please note that these meeting guidelines may be modified in the future. The NIDCD encourages investigators to check this site periodically for any future changes in these guidelines.
DSMB recommendations should be based on results from the trials being monitored as well as on published data from other studies. It is the responsibility of the coordinating center, study chair, study investigators, NIDCD staff, and individual DSMB members to ensure that the DSMB is kept apprised of non-confidential outcome results from other related studies as they become available.
No action on the recommendations is to be taken by the study leadership until the recommendations have been reviewed and accepted by the NIDCD. DSMB recommendations that a study change for patient safety or efficacy reasons, or that a study be closed early due to slow accrual or other reasons should be communicated to the study leadership and the NIDCD immediately following the DSMB meeting.
It is the responsibility of the study chair and coordinating center, in collaboration with the NIDCD, to review the recommendation s and to implement the change s as expeditiously as possible. Confidentiality must be maintained during these discussions. If a recommendation is made to change a protocol for reasons other than patient safety or efficacy or for slow accrual, the DSMB will provide an adequate rationale for its decision.
In the absence of disagreement, the coordinating center will be responsible for amending the protocol and notifying the clinical centers as expeditiously as possible. It is the responsibility of the local clinical center directors to notify their local IRBs of any protocol changes. Confidential outcome data should not be made available to individuals outside of the DSMB. No communication, either written or oral, of the deliberations or recommendations of the DSMB will be made outside of the DSMB except as provided for in these guidelines.
Outcome results are strictly confidential and must not be divulged to any non-member of the DSMB. Each member of the DSMB, including non-voting members, must sign a statement of confidentiality. Conflict of interest can include financial interest, professional interest in the sense of the trial outcome benefiting the individual professionally , proprietary interest, and miscellaneous interest as described in the NIH Grants Policy and 45 CFR Part The NIDCD and the study leadership will make collaborative decisions regarding service by individuals with potential conflicts of interest or the appearance of conflicts of interest.
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We are in the process of retroactively making some documents accessible. If you need assistance accessing an accessible version of this document, please reach out to the Section Help Desk. The Department may not cite, use, or rely on any guidance that is not posted on the guidance repository, except to establish historical facts.
Introduction National Institutes of Health NIH policy stipulates that a system be in place for appropriate oversight and monitoring to ensure the safety of participants and the validity of data in all NIH-sponsored or NIH-conducted clinical studies. NIH program staff. Responsibility for Data and Safety Monitoring NIDCD-supported clinical trial monitoring activities should be commensurate with the risks, size, and complexity of the study.
An independent medical monitor for participant safety and an independent data monitor for data integrity and protocol compliance. Low-Risk Interventions The potential of these interventions to cause physical or psychological harm is low.
For example: Risks that are no greater than those encountered in routine medical care or procedures. Some behavioral interventions that are not distressful, harmful, painful, or invasive to study participants. Software devices, including software applications unlikely to cause injury to the operator and study participants. Some physical therapy interventions with a low level of exertion and discomfort.
Exploratory Studies Exploratory studies, such as Phase I studies, are usually small, unblinded clinical trials conducted early in the development of an intervention.
Clinical Use Studies Clinical use studies, such as Phase III clinical trials, are large pivotal studies intended to provide formal statistical demonstration of efficacy and to monitor adverse events.
Higher-Risk Interventions Exploratory Studies A typical exploratory clinical trial evaluating the safety of a new agent, device, or procedure such as a Phase I study involves relatively high risk to a small number of participants.
Confirmatory Studies A confirmatory clinical trial evaluating the clinical activity of exposure such as a Phase II trial typically follows early exploratory studies and provides more information regarding risks, benefits, and monitoring procedures.
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