Determining what to return

Step 1: During the study, when are you collecting data?

Consider the entire clinical trial lifecycle for a participant:

Step 2: What kinds of data will be generated during each period?

Think about the kinds of tests you will perform during each of the above periods:

  • Study arm assignment
  • Laboratory tests
  • Diagnostic Imaging
  • Genetic sequencing
  • Physical or visual examinations
  • Socio-behavioral
  • Surveys and questionnaires
  • Digital or mobile health results
  • Patient-reported outcomes (PROs)
  • Exploratory results

Step 3: Consider the following questions/domains for each data type during each study period to determine whether to return and what plans must be made to return:

A. URGENCY

  • Is there a possibility for a result to require urgent medical attention?
    • Example: A “routine” blood pressure found to be 220/120 mmHg
    • Example: A participant reports suicidal ideation
  • Is there a possibility for an urgent unanticipated finding to be identified while testing for something else?
    • Example: A mass is discovered on a routine Chest X-ray

NO

Next data type

YES

  • This result should be returned ASAP
  • A plan must be made ahead of time for how to return this result, especially regarding:
    • how the study team will ensure compliance with necessary regulations (e.g. CLIA)
    • whether the result will be returned to the participant or a medical provider/other appropriate person
  • See more here about returning urgent results.

B. ACTIONABILITY

Does the result have established health or other personal implications and is actionable, but not urgent?

  • Example: A Hemoglobin AIC (or HbA1c) blood test, a measure of average blood sugar, is above normal, and may indicate diabetes or pre-diabetes.
  • Example: Genetic screening of an individual who has been personally unaffected by cancer returns the presence of BRCA1, a breast cancer susceptibility gene.

NO

Next data type

YES

  • This result should be returned to participants
  • A plan should be made ahead of time for how and when to return this result – see more here about returning actionable results.

C. PERSONAL VALUE

Is the result something that could be considered meaningful or valuable to the participant despite not being currently actionable?

  • Example: Genetic screening of a normal individual returns cystic fibrosis carrier status.
  • Example: The participant is found to have Gilbert’s syndrome with an abnormal bilirubin secondary to a variant of a gene but one that does not cause liver disease. It is important to know, however, so that unnecessary tests are not performed.
  • Example: The participant is found to have a rare blood type.

NO

Next data type

YES

  • This result should be returned to participants if feasible
  • Feasibility is dependent on the study and the priorities of the study population, and should be considered on a study-by-study basis.
  • A plan should be made ahead of time for how and when to return this result – see more here about returning personally valuable results.

D. INTERPRETATION LIMITATIONS

Is the result not known to have any health implications?

  • Example: A minimally high-density lipoprotein (HDL) of uncertain significance.
  • Example: Initial genetic research studies that are trying to uncover associations between differences in our DNA and response to an investigational drug.

YES

  • If returning this result, do so with adequate explanation of the limits of current knowledge.
  • See more here about returning results with no known implications.