We are dealing with a serious problem. NIH-funded scientists are not publicizing nearly half of the trials they conduct and complete in a timely manner. This is an unacceptable state of affairs. Our purpose in defining clinical trials as we do is to improve dissemination and transparency. The bottom line: if public money is going to be spent to conduct experiments on people, you are expected to report the results. It is not right to conduct experiments on people (at taxpayer expense) and keep the results secret.
In our policy notice on the Dissemination of NIH Funded Clinical Trial Information we stated, “We disagree with commenters who suggested that there is no need for coverage of certain types of trials, such as early exploratory trials, small trials, trials assessing only safety, or trials that terminate before reaching enrollment targets. The benefits of transparency and the need to fulfill the ethical obligation to participants is as relevant to these types of trials as to any other type.”
Clinical trials are clinical research studies involving human participants assigned to an intervention in which the study is designed to evaluate the effect(s) of the intervention on the participant and the effect being evaluated is a health-related biomedical or behavioral outcome.
We recognize that it may be difficult to determine whether two or more closely related protocols should be considered a single study. Generally, if you have research activities that use the same human subjects population, follow the same core research protocol and procedures, and intend to combine the data for analysis in aggregate, this would be considered a single study for the purposes of the PHS Human Subjects and Clinical Trial form.
When in doubt, at the time of application NIH supports grouping studies that use the same research protocol and the same human subjects population into a single study record, to the extent that the information provided is accurate and understandable to NIH staff and reviewers. You are also encouraged to discuss how to group your studies with your NIH Program Officer.
For studies that will need to register and report in ClinicalTrials.gov, keep in mind that each ClinicalTrials.gov record should be a unique study record in the PHS Human Subjects and Clinical Trial form.
If any outcome is health-related and the answers to the four questions are all yes, then the study meets the clinical trial definition. You should note, though, that all NIH-funded research investigating biomedical or behavioral outcomes is considered to be health-related. Hence, if the outcome is biomedical or behavioral, the study may be a clinical trial (if the answers to the other three questions are “yes”). Many clinical trials are “mechanistic” or “exploratory” falling outside the realm of efficacy or effectiveness trials.
NIH considers the two definitions to have the same meaning.
Revised Common Rule §__.102(b): “Clinical trial means 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 the interventions on biomedical or behavioral health-related outcomes.”
NIH clinical trial definition: “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.” (Oct 23, 2014)
An intervention is defined as a manipulation of the subject or subject’s environment for the purpose of modifying one or more health-related biomedical or behavioral processes and/or endpoints. Examples include: drugs/small molecules/compounds; biologics; devices; procedures (e.g., surgical techniques); delivery systems (e.g., telemedicine, face-to-face interviews); strategies to change health-related behavior (e.g., diet, cognitive therapy, exercise, development of new habits); treatment strategies; prevention strategies; and, diagnostic strategies.
No; measurements are used to collect data, while interventions are used to modify health-related endpoints. A manipulation or modification in one’s behavior or environment for the purpose of measurement alone is not considered a clinical trial.
A manipulation or task is an intervention if it is used to modify a health-related biomedical or behavioral outcome. However, a manipulation or task used expressly for measurement, and not modification, would not be an intervention.
While the vast majority of NIH-funded studies are health related, a few are not. For example, a study that evaluates if enrollment in a summer internship program alters the student’s opinions on their educational pathway would not be assessing a health-related biomedical or behavioral outcome.
Applications will continue to be assigned to study sections based on the topic of science. We will take all needed steps to assure that every application is reviewed by peers with the appropriate expertise.
No; having a plan for addressing incidental findings does not determine whether a study is considered to be a clinical trial. To determine whether your study meets the NIH clinical trial definition, please refer to the four questions above that outline the criteria.
It depends. Studies eliciting opinions or preferences in the absence of an intervention are not considered to be clinical trials. However, studies that gather opinions from participants after an experimental manipulation or intervention, may be clinical trials.
No; a study must be designed to evaluate the effect of the intervention on the human participant to meet the NIH clinical trial definition. In this example, the study is designed to compare the functionality of devices, and not the effect of the devices on the participant. (Case Studies https://grants.nih.gov/policy/clinical-trials/case-studies.htm#case8a).
Yes; in these studies, both the healthcare providers and patients are human participants, and the healthcare providers become part of the intervention. The study is considered to be a clinical trial as long as all other elements of the NIH clinical trial definition are met. (See Case Study https://grants.nih.gov/policy/clinical-trials/case-studies.htm#case20)
Yes; the NIH clinical trial definition specifies that there must be one or more human participants involved in the study. Therefore, single case studies or N-of-1 trials are clinical trials. The study is considered to be a clinical trial if all elements of the NIH clinical trial definition are met.
Yes; if the ancillary study adds an additional prospectively assigned intervention to patients or a sub-population of patients within the larger clinical trial and all elements of the NIH clinical trial definition are met.
No; if the ancillary study is only adding additional measures to an existing clinical trial.
Determine whether an ancillary study is a clinical trial by answering the four questions that define NIH clinical trials based on the information about the ancillary study alone, regardless of the clinical trial status of the parent trial.
No; studies using correlational designs to prospectively associate biomedical or behavioral parameters with other health-related measures, but do not involve an intervention, do not meet the NIH clinical trial definition.
No; studies using correlational designs to prospectively associate biomedical or behavioral [MQ1]parameters with other health-related measures, but do not involve an intervention, do not meet the NIH clinical trial definition.
It depends. Studies that are mechanistic in nature but do rely on an intervention to modify a health-related outcome may be considered a clinical trial. However, studies that do not use an intervention, would not be a clinical trial.
Studies need not include a comparison group to meet the NIH clinical trial definition. As long as all of the elements of the NIH clinical trial definition are met, the study would be considered to be a clinical trial.
No; if care is not part of the research protocol and there are no additional interventions in the study, then this would be classified as an observational study, and would not meet the NIH definition of a clinical trial. However, if standard or routine clinical care is modified for the purpose of the study (e.g. dosage, frequency, or timing of treatment), the study would be considered a trial.
Phase I device studies may or may not meet the NIH definition of a clinical trial. The NIH definition of a clinical trial encompasses many ACTs and also many non-ACTs, including phase 1 trials of FDA-regulated drug and biological products, small feasibility studies of FDA-regulated device products, and studies of any intervention not regulated by the FDA, e.g., behavioral interventions. See our case studies to learn more.