NIH Definition of Clinical Trial Case Studies

The case studies provided below are designed to help you identify whether your study would be considered by NIH to be a clinical trial. Expect the case studies and related guidance to evolve over the upcoming year.

 


 
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The simplified case studies apply the following four questions to determine whether NIH would consider the research study to be a clinical trial:

  • Does the study involve human participants?
  • Are the participants prospectively assignedThe term "prospectively assigned" refers to a pre-defined process (e.g., randomization) specified in an approved protocol that stipulates the assignment of research subjects (individually or in clusters) to one or more arms (e.g., intervention, placebo, or other control) of a clinical trial. to an intervention?
  • Is the study designed to evaluate the effect of the interventionAn "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. on the participants?
  • Is the effect being evaluated a health-related biomedical or behavioral outcome A "health-related biomedical or behavioral outcome" is defined as the pre-specified goal(s) or condition(s) that reflect the effect of one or more interventions on human subjects’ biomedical or behavioral status or quality of life. Examples include: positive or negative changes to physiological or biological parameters (e.g., improvement of lung capacity, gene expression); positive or negative changes to psychological or neurodevelopmental parameters (e.g., mood management intervention for smokers; reading comprehension and /or information retention); positive or negative changes to disease processes; positive or negative changes to health-related behaviors; and, positive or negative changes to quality of life.

If the answer to all four questions is “yes,” then the clinical study would be considered a clinical trial according to the NIH definition. 

Note that studies of surveys, questionnaires, user preferences, and studies involving focus groups are not clinical trials. Likewise, studies that involve secondary research with biological specimens or health information are not clinical trials. Finally, educational studies, such as those with outcomes focusing on memorization, or retention and recall of information to assess teaching methods, are not clinical trials. 

 

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Biomedical Studies

Case #1:

The study involves the recruitment of research participants to receive one of two approved drugs. It is designed to measure the effect of the drugs on the level of a protein in the blood of the participants.

Case #2:

The study involves the recruitment of research participants with condition Y to receive a drug that has been approved for another indication. It is designed to measure the drug’s effects on the level of a biomarker associated with the severity of condition Y.

Case #3:

The study involves the recruitment of research participants with condition X to receive investigational compound A. It is designed to assess the pharmacokinetic properties of compound A.

Case #4a:

The study involves the recruitment of research participants with disease X to receive an investigational drug. It is designed to assess safety and determine the maximum tolerated dose of the drug.

Case #4b:

The study involves the recruitment of research participants with disease X to receive a chronic disease management program. It is designed to assess usability and to determine the maximum tolerated dose of the chronic disease program (e.g., how many in-person and telemedicine visits with adequate adherence).

Case #5:

The study involves the recruitment of research participants with disease X to receive either an investigational drug or a placebo. It is designed to evaluate the effectiveness of the investigational drug to relieve disease symptoms.

Case #6:

The study involves the recruitment of research participants with disease X to receive an investigational drug. It is designed to assess whether there is a change in disease progression compared to baseline. There is no concurrent control used in this study.

Case #7a:

The study involves the recruitment of research participants with disease X to test an investigational in vitro diagnostic device (IVD). It is designed to evaluate the ability of the device to measure the level of an antibody in blood.

Case #7b:

The study involves the recruitment of research participants with disease X to be evaluated with an investigational in vitro diagnostic device (IVD). It is designed to evaluate the ability of the device to measure the level of an antibody in blood, and the investigators plan to measure the impact of this knowledge on the treatment of disease.

Case #8a:

The study involves the recruitment of research participants with disease X. It is designed to compare the performance of approved devices A and B, both of which are used in clinical practice, to measure disease markers. Device A will be used in half of the patients; device B will be used in the other half.

Case #8b:

The study involves the recruitment of research participants suspected to have disease X. It is designed to compare the ability of approved devices A and B to diagnose the disease and inform the management of clinical outcomes. Device A will be used in half of the patients; device B will be used in the other half.

Case #8c:

The study involves the recruitment of research participants suspected to have disease X. It is designed to compare the ability of commercial sensors A and B to improve diagnosis of the disease and inform the management of clinical outcomes. Device A will be used in half of the patients; device B will be used in the other half.

Case #9:

The study involves the recruitment of healthy volunteers who will be deprived of sleep for a period of time and have blood drawn. It is designed to determine whether the levels of stress hormones in blood rise in response to sleep deprivation.

Case #10a:

The study involves the analysis of de-identified, stored blood samples and de-identified medical records of patients with disease X who were treated with an approved drug. The study is designed to evaluate the level of a protein in the blood of patients that is associated with therapeutic effects of the drug.

Case #10b:

The study involves the analysis of identifiable, stored blood samples and identified medical records of patients with disease X who were treated with an approved drug. The study is designed to evaluate the level of a protein in the blood of patients that is associated with therapeutic effects of the drug.

Case #11:

The study involves the recruitment of a healthy volunteers whose blood is drawn for genomic analysis. It is designed to identify the prevalence of a genetic mutation in the cohort and evaluate potential association between the presence of the mutation and the risk of developing a genetic disorder.

Case #12:

Physicians report that some patients being treated with drug A for disease X are also experiencing some improvement in a second condition, condition Y. The study involves the recruitment of research participants who have disease X and condition Y and are being treated with drug A. The participants are surveyed to ascertain whether they are experiencing an improvement in condition Y.

Case #13a:

The study involves the recruitment of patients with disease X who are receiving one of three standard therapies as part of their clinical care. It is designed to assess the relative effectiveness of the three therapies by monitoring survival rates using medical records over a few years.

Case #13b:

The study involves the recruitment of research participants with disease X vs. healthy controls and comparing these participants on a range of health processes and outcomes including genomics, biomarkers, laboratory measures, etc. to explore differences that may be relevant to the development of disease X.

Case #14:

The study involves the recruitment of healthy volunteers for a respiratory challenge study. The study evaluates the severity and mechanism of the immune response to combinations of allergens introduced via inhalation.

Case #15:

The study involves the recruitment of research participants with Alzheimer’s disease (AD) to evaluate the effects of an investigation drug on memory, and retention and recall of information.

Behavioral Studies

Case #16:

The study involves the recruitment of individuals to receive a new behavioral intervention for sedentary behavior. It is designed to measure the effect of the intervention on hypothesized differential mediators of behavior change.

Case #17a:

The study involves the recruitment of patients with disease X to be evaluated with a new executive function task. It is designed to evaluate the ability of the new task to measure executive function.

Case #17b:

The study involves the recruitment of research participants with disease X to be tested with a new executive memory task. It is designed to evaluate the ability of the task to measure executive function and determine cut scores or clinically meaningful scores by evaluating differential treatment course among research participants.

Case #18:

The study involves the recruitment of healthy volunteers who will perform working memory tasks while an fMRI is performed. It is designed to determine the brain functions involved in working memory.

Case #19:

The study involves the recruitment of research participants with CHF who are were hospitalized before or after the Medicare incentives to reduce re-hospitalizations. Morbidity, mortality, and quality of life of these participants are evaluated to compare the effects of these Medicare incentives on these outcomes.

Case #20:

The study involves the recruitment of healthcare providers to assess the extent to which being provided with genomic sequence information about their patients informs their treatment of those patients towards improved outcomes.

Case #21:

The study involves the recruitment of research participants with a behavioral condition to receive either an investigational behavioral intervention or a behavioral intervention in clinical use. It is designed to evaluate the effectiveness of the investigational intervention compared to the intervention in clinical use in reducing the severity of the obsessive compulsive disorder.

Case #22:

The study involves the recruitment of healthy children who will be presented with a series of learning activities. It is designed to evaluate the children’s ability to retain and retrieve specific information.

Case #23:

The study involves the recruitment of physicians to assess whether a new app, which cues directed interviewing techniques, is better than an existing app at assisting physicians in identifying families in need of social service support. The number of community service referrals will be measured.

Case #24:

The study involves evaluating different types of printed announcements to identify the best designs for ensuring comprehension and retention of information in adults. Visitors to public libraries will be selected at random and asked to read one of the two announcements and then to take a short survey to elicit their perspectives about readability.

Case #25:

The study involves randomly assigning adults to different processes for informed consent in order to assess preferences for interactive and multimedia components during informed consent. The study measures participant preferences.

Case #26:

The study involves randomizing individuals to different processes for informed consent. It is designed to assess the effectiveness of interactive and multimedia components in enhancing participants’ understanding of the study’s purpose and procedures.

Case #27:

The study involves the recruitment of parents to participate in focus groups to discuss topics related to parental self-efficacy and positive parenting behaviors. It is designed to gather information needed to develop an intervention to promote parental self-efficacy and positive parenting behaviors.

Case #28:

The study involves the recruitment of healthy volunteers to test a new behavioral intervention. It is designed to evaluate the effect of a meditation intervention on adherence to exercise regimens and quality of life to inform the design of a subsequent, fully-powered trial.

Case #29:

The study involves the recruitment of healthy volunteers to test a new behavioral intervention. It is designed to evaluate the acceptability of the intervention. The outcome is acceptability, not efficacy, of the intervention to the target providers and their patients.

Case #30a:

The study involves the recruitment of healthy family members of patients hospitalized for disease X to test two CPR training strategies. Participants will receive one of two training strategies. The outcome is improved CPR skills retention.

Case #30b:

The study involves the recruitment of research participants in three different communities (clusters) to test three CPR training strategies. The rate of out-of- hospital cardiac arrest survival will be compared.

Case #31a:

A study involves the recruitment of school children to evaluate two different tools for monitoring food intake. Food consumption behavior will be measured by asking children to activate a pocket camera during meals and to use a diary to record consumed food. The accuracy of the two food monitoring methods in measuring energy intake will be assessed.

Case #31b:

A study involves the recruitment of school children to evaluate two different tools for monitoring food intake. Food consumption behavior will be measured by asking children to activate a pocket camera during meals and to use a diary to record consumed food. Changes to eating behavior will be assessed.

Case #32:

A study involves the recruitment of children at two schools to monitor eating behavior. Children’s food choices will be monitored using a remote food photography method. Food consumption and the accuracy of food monitoring methods will be assessed.

Case #33:

A study involves the recruitment of children at two schools to evaluate their preferences for graphics and colors used in healthy food advertisements. Children will be presented by multiple health advertisement and their preferences for graphics and colors will be assessed.