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Return of Results (ROR)

Points to Consider for Research Conducted Using NBSTRN Resources

This is intended to address research conducted using the Virtual Repository of Dried Blood Spots (VRDBS), Longitudinal Pediatric Data Resource (LPDR), or other NBSTRN resources.  Prior to beginning a research project, researchers should consider what to do if their work finds information of possible clinical utility to an individual or population in the study. When applicable, researchers should have an IRB approved plan to manage ROR.

Frequently, research in this area may be conducted with anonymous or aggregate de-identified data without specific informed consent. Thus, in many cases, it may not be possible for the researcher to return individual results to research participants. Even in research using anonymous or de-identified data; however, there may be rare cases where results have clear clinical significance for individuals or a population, and where return of results (ROR) would be beneficial for the individual or the population.  If de-identified data have been used, and if the state has retained individual identifiers, the state may be able to act as an “Honest Broker,” to re-identify individuals.  Alternatively, when anonymous data have been used, the State may be able to identify a specific population that may benefit from knowledge of the research results. Researchers should have a plan, in cooperation with the state as Honest Broker and the appropriate IRB, to consider whether, when, and how results ought to be returned. If return of results is part of the plan; the rules, roles, and responsibilities of all parties involved should be clearly defined in the research protocol.

Whether and how results should be returned to participants varies greatly depending on the research methods (e.g. population data), the information obtained (e.g. how likely to impact an individual’s health), whether the samples are identifiable, and the agreements made in any consent for a specific protocol. The table below provides a framework for approaching ROR in different types of research.

Types of Results Available to Return

  • Anonymous: Aggregate Only
  • De-Identified: Aggregate and/or Individual
  • Identified/Informed Consent: Aggregate Only

Planning for Returning Results

Researcher should have a plan for managing aggregate results including:
  • Clinically critical results for a population
  • Clinically uncertain results for a population
  • Results that my have a social/cultural impact on a community
Notes:
  1. The plan may be that no results will be returned, but there should be a valid IRB-approved rationale.
  2. The plan could be created in cooperation with the State or other Honest Broker, if applicable.

In addition to having a plan for aggregate results (if applicable), the researcher should have a plan for whether or not to return clincally useful results for an individual.

Notes:

  1. Returning individual results from de-identified data would require state involvement to re-link the data to individuals. Researchers should work with their state to discuss any potential plans to return these kinds of results.
  2. If the plan is that no results will be returned, the reason(s) should be explained and approved by the IRB.
  3. The plan should be created in cooperation with the State or Honest Broker, if applicable.
In addition to having a plan for aggregate results (if applicable) the researcher should have a plan for returning:
  • Clinically useful results for an individual and whether or not to return
  • Clinically uncertain results for an individual
Notes:
  1. If prior informed consent is obtained, then the researcher's IRB-approved plan will address whether and how they are giving individuals the option of whether and what information to receive as part of the informed consent process.
  2. The plan may be that no results will be returned.
  3. The plan should be created in cooperation with the State or Honest Broker, if applicable.

Case Example

Anonymous research that discovers an increased risk of a treatable condition in the research population, such as living near a chemical plant increases the risk of cancer.

Plan: There should be a plan to publicize the results or provide them to the relevant Department of Public Health so that the results can be provided to the population.

De-identified research where the Department of Public Health, or Honest Broker, could identify the subject but the researcher cannot. Example, research with a waiver of consent where a result with highly significant implications for a specific, de-identified, subject is obtained.

Plan: Researcher finds something that could lead to premature death of an individual. Researcher has a plan to inform the Department of Public Health so that the department and the appropriate IRB can determine whether it is appropriate to contact the subject's family and inform them of the results.

Research with identified subjects:

Plan: Describe the research and tell potential subjects what you plan to do about any results you obtain. If you do not plan to return results, say that, so the subject has an opportunity to decide if they wish to participate. If subjects have the opportunity to choose whether or not they wish to be recontacted about clinically useful and/or clinically uncertain results, say that. You can include an option to be contacted via the informed consent form. If you will not look at results for a lengthy period of time say so.

Other points to consider:

  1. Returning Results in the Clinical Setting: Several groups have published lists of clinically actionable genetic information:
    1. ACMG Recommendations for Reporting of Incidental Findings in Clinical Exome and Genome Sequencing
    2. ACMG Incidental Findings in Genomics: A Clarification
    3. Exploring Concordance and Discordance for Return of Incidental Findings From Clinical Sequencing
  2. Targeted, Anticipated or Unanticipated Results:  Researchers should have an ROR plan whether a result is “targeted,”  “anticipated,” or “unanticipated.” “Targeted” means results that are the focus of the research, “anticipated”  means results that are known to occur with the research being done but are not the target of the research (for example parenthood, genetic carrier status, etc.), and  “unanticipated”  means results that were not contemplated, expected, or the focus of the research.
  3. Reporting Results to IRB and/or State/Local Public Health:  Researchers should consider how and when to report results to IRB and State/local public health department and work out a mutually acceptable plan ahead of time that is included in the IRB approved protocol.   The IRB may have mandatory requirements. The State(s) may have rules that researchers will need to know and follow.  If there is a material transfer agreement it may have required actions.
  4. Returning Research Lab Results:  When possible or appropriate, researchers should consider choosing analytical methods that minimize the possibility of unanticipated and/or undesired findings.
  5. Use of CLIA-Approved Labs:If there is an intention to return results, then research lab results should be confirmed by CLIA-approved clinical labs when possible.  Researchers should have a plan for ROR when there is no CLIA-approved clinical test available.

Developed by the NBSTRN Bioethics and Legal Issues Workgroup